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Psychiatry Online

  • February 01, 2024 | VOL. 181, NO. 2 CURRENT ISSUE pp.83-170
  • January 01, 2024 | VOL. 181, NO. 1 pp.1-82

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Trauma, Resilience, Anxiety Disorders, and PTSD

  • Ned H. Kalin , M.D.

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Stress and trauma are well known to be critical factors in the development and maintenance of psychopathology. In some stress-related disorders, such as anxiety and depression, stress can play an etiological role, whereas in other disorders like schizophrenia, stress can precipitate and exacerbate symptoms. Stress occurring early in life in the form of traumatic events is a transdiagnostic risk factor for developing psychopathology, whereas posttraumatic stress disorder (PTSD) is a disorder that is specifically defined as a maladaptive response to traumatic events. In the midst of the COVID-19 pandemic, and certainly to no one’s liking, we currently are involved in a naturalistic experiment linking stress to mental suffering and psychopathology.

Most of us have never experienced stressors of the magnitude and length associated with the global COVID-19 pandemic. Because the pandemic has been so prolonged, and in part as a way to cope, many of us have become inured to its catastrophic effects. It is mind boggling that we have begun to accept as commonplace the fact that 3,000 Americans per day are dying from COVID-19 or that the economic consequences are so dire that 16% of adults with children report not having sufficient food ( 1 ). Although it may be obvious, it is important to enumerate why the COVID-19 pandemic represents the perfect storm of stressors and traumatic events:

A long-term sense of uncertainty about the future coupled with a sense of uncontrollability.

Concerns about contracting COVID-19, becoming gravely ill, and dying.

Worries about losing loved ones and friends, and the grief associated with real losses.

The trauma associated with being gravely ill with COVID-19.

Prolonged physical separation and social isolation from family and friends.

Disruption of regular routines, including work and school for children.

Losses of jobs, business failures, and the profound economic consequences.

Lack of trust in leadership to effectively deal with the crisis.

As mental health care providers, we are in the uniquely challenging position of both personally experiencing the disruptive influences of chronic stress associated with the pandemic and working with patients and other vulnerable individuals to mitigate the consequences of the stress and tragedies that they are experiencing. It is critical to underscore the need to provide additional resources to underprivileged and marginalized individuals, as they are particularly vulnerable to the direct and indirect consequences of the COVID-19 pandemic. For example, Black and Latino households are twice as likely as White households to experience food insufficiency during the pandemic.

The focus of this issue of the Journal is highly relevant, as it provides new insights into the neural alterations associated with trauma, resilience, anxiety disorders, and PTSD as well as insights into new, promising treatment strategies. Dr. Yuval Neria, a PTSD expert from Columbia University, reviews neuroimaging findings in relation to PTSD and addresses how they may relate to the heterogeneity of PTSD symptom presentation and inform selective treatment approaches ( 2 ). Dr. Yair Bar-Haim from Tel Aviv University and his colleagues present a thought-provoking commentary suggesting that symptoms associated with the intrusive reexperiencing of traumatic events should be prioritized as a focus of research efforts to elaborate mechanisms underlying responses to trauma and PTSD ( 3 ). Dr. Dylan Gee and Paola Odriozola from Yale University coauthor a review that uses a translational neuroscience approach to discuss learning mechanisms relevant to the maladaptive regulation of fear and anxiety. In addition to considering conditioned fear learning and extinction, this review emphasizes the importance of safety signal learning, describes its underlying mechanisms, and speculates about the potential utility of using safety signal learning approaches in treating youths with anxiety disorders ( 4 ).

Is Inducing Anxiety in Healthy Individuals a Valid Approach for Understanding Pathophysiological Processes in Patients With Anxiety Disorder?

Numerous studies in healthy individuals have used threat-related paradigms in combination with neuroimaging to characterize the neural correlates of adaptive anxiety responses. The findings from these studies have frequently been used to draw inferences about alterations in neural activation that are associated with maladaptive anxiety responses in individuals with anxiety disorders. Chavanne and Robinson focus on determining whether studying healthy individuals under conditions of threat is a valid approach for understanding brain processes relevant to psychopathology ( 5 ). In their study, the authors first performed a meta-analysis on neuroimaging findings from studies in which patients with anxiety disorders were compared with control subjects when exposed to emotion-related paradigms. The results of this analysis were further compared with a meta-analysis of imaging findings assessing neural responses induced by unpredictable threat paradigms in healthy individuals. Across healthy individuals and those with anxiety disorders, increased activation was found in the insula, cingulate cortex, medial prefrontal cortex, and periaqueductal gray. There were also some differences between individuals with specific disorders and healthy control subjects. Similarities in neural activation between healthy individuals exposed to threat and individuals with anxiety disorders appeared to be greatest for individuals with specific phobias and were least similar for those with generalized anxiety disorder. In an editorial, Dr. Alexander Shackman from the University of Maryland and Dr. Andrew Fox from the University of California, Davis, discuss these findings in relation to the validity of using healthy subjects to understand pathophysiological processes in patients with anxiety disorders. They also point to additional work that needs to be done with animal models and humans to further develop an understanding of the mechanisms underlying pathological anxiety ( 6 ).

Using Brain Network Connectivity to Estimate the Severity of Dissociative Symptoms

Dissociative symptoms are a hallmark of PTSD and can be very disabling. The study by Lebois et al. ( 7 ) presents data demonstrating the capacity to use machine learning with functional connectivity MRI data to modestly estimate individual differences in dissociative symptoms in women with PTSD. In their study involving 65 women, the authors demonstrated that they could estimate about 24% of the variance in an individual’s dissociative symptom severity by using the functional connectivity data. Hyperconnectivity between regions of the default mode network and the frontoparietal network appeared to contribute most to this prediction. Of importance, this brain network connectivity–based estimate controlled for childhood trauma and PTSD symptom severity, suggesting that the connectivity patterns identified to be associated with dissociative symptoms involved distinct neural alterations. In addition to providing a better understanding of the neural underpinnings of dissociative symptoms, the results of this study suggest that in the future it may be plausible to use brain-based neural connectivity measurements as an objective proxy for subjective reports of dissociative symptoms. In his insightful editorial, Dr. Vinod Menon from Stanford University discusses how the functions of the default mode network and frontoparietal network, and their interactions, may relate to the subjective experience of dissociation ( 8 ). In addition, he suggests that interventions aimed at components of the salience network, such as the anterior cingulate cortex, may ameliorate dissociative symptoms by affecting interactions between the default mode and frontoparietal networks.

Patterns of Cortical Thinning Are Shared Across Individuals With Internalizing, Externalizing, and Thought Disorder–Related Symptoms

Brain structural alterations are commonly reported in patients across various psychiatric diagnoses. Romer and colleagues ( 9 ) present data demonstrating overlapping patterns of reduced cortical thickness in individuals with internalizing symptoms (e.g., depression and anxiety), externalizing symptoms (e.g., substance abuse and antisocial behavior), and thought disorder–related symptoms (e.g., delusions and hallucinations). This study used structural imaging data to assess cortical thickness and cortical surface area from 45-year-old individuals who were part of the longitudinally studied Dunedin Cohort. In addition to demonstrating cortical thinning across diagnostic domains, patterns of cortical thinning were related to the general psychopathology dimensional score known as the p factor. It is important to keep in mind that these relations do not address issues of causality. Based on these data, the authors argue that the transdiagnostic nature of pervasive cortical thinning further supports the value of a broad and general approach to study the relations between psychopathology and brain alterations.

Resilience During Pregnancy Is Associated With Increased Telomere Length in Newborns

Telomeres are strands of nucleotides at the ends of chromosomes that have various functions, including protecting the chromosome from degradation. In general, shortened telomeres have been associated with stress exposure, various illnesses, and aging. Verner and colleagues ( 10 ) studied 656 mother-infant dyad pairs and, by using multiple behavioral measures collected during pregnancy, computed factors associated with stress and positivity. Telomere length was assessed in leukocytes collected from cord blood at birth. The findings demonstrate an association between individual differences in pregnant mothers’ stress factor and shorter telomere length in newborns. In contrast, individual differences in the positivity factor during pregnancy were associated with increased telomere length. By statistically accounting for the effects of positivity on stress, the authors derived what they considered to be a measure of resilience, and by using this measure, they demonstrate that maternal resilience is associated with increased telomere length in newborns. The findings from this study are exciting as they suggest that resilience during pregnancy has important implications at the cellular and molecular level for newborns and for their development. In her editorial, Dr. Stacy Drury from Tulane University further discusses the relevance of telomere length and function in relation to health and disease. She also presents possible mechanisms by which stress during pregnancy might affect offspring telomeres ( 11 ).

Ketamine Treatment for PTSD

New and effective treatments are needed for patients with PTSD. Feder et al. ( 12 ) report findings from a randomized clinical trial examining the effects of repeated intravenous ketamine infusions on symptoms in PTSD patients. Ketamine is an N -methyl- d -aspartate receptor antagonist with effects on numerous other systems, including opiate receptors, and when administered in subanesthetic doses, it is effective in rapidly decreasing depressive symptoms. The authors of the present study previously reported that a single dose of ketamine had positive short-term effects in PTSD patients, and they now extend this work by assessing the effects of repeated ketamine administration as a means to provide longer-term efficacy. In the study, 30 chronically ill PTSD patients were randomly assigned to receive, over a 2-week period, either six infusions of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) as an active placebo. In the 29 individuals who completed the study, 15 received ketamine. The findings demonstrated rapid responses to ketamine. When assessed at 1 and 2 weeks, ketamine was significantly and robustly more effective in reducing symptoms compared with midazolam. It is important to note that although the repeated ketamine infusions were highly effective, the median time to the loss of the ketamine response was 27.5 days. In their editorial, Dr. Murray Stein from the University of California, San Diego, and Dr. Naomi Simon from New York University emphasize the need to develop more effective treatments for PTSD. They also comment on the renewed interest in psychedelic drugs as therapeutic agents and the possible mechanisms by which ketamine may work in relation to modifying the recall of traumatic memories associated with PTSD ( 13 ).

Conclusions

The imperative to understand how stress and trauma increase the vulnerability to develop psychiatric illnesses could not be more relevant and timelier as the world’s population is experiencing unprecedented levels of stress, trauma, fear, anxiety, and grief. It is also extremely important to focus on, and understand, the factors that promote resilience, as we witness the remarkable capacities of individuals to endure, cope with, and overcome the adversity and challenges presented by the pandemic.

This issue of the Journal provides a comprehensive focus on new research findings relevant to these issues. Highlights from the reports in this issue include findings that there is evidence supporting the dimensionality of anxiety, as there is shared activation of anxiety-related neural circuitry between healthy individuals and those with anxiety disorders; that resilience during pregnancy is associated with greater “healthier” telomere length in newborns; that focusing on safety learning may be a fruitful treatment approach for anxiety disorders, especially for children; that machine learning methods can be employed with imaging data to predict the severity of dissociative symptoms in PTSD patients; and that repeated ketamine administration over a 2-week period robustly decreases PTSD symptoms.

Disclosures of Editors’ financial relationships appear in the April 2020 issue of the Journal .

1 Center on Budget and Policy Priorities: Tracking the COVID-19 recession’s effects on food, housing, and employment hardships. https://www.cbpp.org/sites/default/files/atoms/files/8-13-20pov.pdf Google Scholar

2 Neria Y : Functional neuroimaging in PTSD: from discovery of underlying mechanisms to addressing diagnostic heterogeneity . Am J Psychiatry 2021 ; 178:128–135 Abstract ,  Google Scholar

3 Bar-Haim Y, Stein MB, Bryant RA, et al. : Intrusive traumatic reexperiencing: pathognomonic of the psychological response to traumatic stress . Am J Psychiatry 2021 ; 178:119–122 Link ,  Google Scholar

4 Odriozola P, Gee DG : Learning about safety: conditioned inhibition as a novel approach to fear reduction targeting the developing brain . Am J Psychiatry 2021 ; 178:136–155 Abstract ,  Google Scholar

5 Chavanne AV, Robinson OJ : The overlapping neurobiology of induced and pathological anxiety: a meta-analysis of functional neural activation . Am J Psychiatry 2021 ; 178:156–164 Link ,  Google Scholar

6 Shackman AJ, Fox AS : Two decades of anxiety neuroimaging research: new insights and a look to the future (editorial). Am J Psychiatry 2021 ; 178:106–109 Link ,  Google Scholar

7 Lebois LAM, Li M, Baker JT, et al. : Large-scale functional brain network architecture changes associated with trauma-related dissociation . Am J Psychiatry 2021 ; 178:165–173 Link ,  Google Scholar

8 Menon V : Dissociation by network integration (editorial). Am J Psychiatry 2021 ; 178:110–112 Abstract ,  Google Scholar

9 Romer AL, Elliott ML, Knodt AR, et al. : Pervasively thinner neocortex as a transdiagnostic feature of general psychopathology . Am J Psychiatry 2021 ; 178:174–182 Abstract ,  Google Scholar

10 Verner G, Epel E, Lahti-Pulkkinen M, et al. : Maternal psychological resilience during pregnancy and newborn telomere length: a prospective study . Am J Psychiatry 2021 ; 178:183–192 Abstract ,  Google Scholar

11 Drury SS : Building resilience for generations: the tip of the chromosome (editorial). Am J Psychiatry 2021 ; 178:113–115 Abstract ,  Google Scholar

12 Feder A, Costi S, Rutter SB, et al. : A randomized controlled trial of repeated ketamine administration for chronic posttraumatic stress disorder . Am J Psychiatry 2021 ; 178:193–202 Link ,  Google Scholar

13 Stein MB, Simon NM : Ketamine for PTSD: well, isn’t that special (editorial). Am J Psychiatry 2021 ; 178:116–118 Abstract ,  Google Scholar

  • Cited by None

research paper about trauma

  • Posttraumatic Stress Disorder (PTSD)
  • Coronavirus/COVID-19
  • Anxiety Disorders

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Open Access

Peer-reviewed

Research Article

Trauma informed interventions: A systematic review

Roles Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Project administration, Resources, Supervision, Writing – original draft, Writing – review & editing

* E-mail: [email protected]

Affiliations School of Nursing, The Johns Hopkins University, Baltimore, Maryland, United States of America, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland, United States of America

ORCID logo

Roles Formal analysis, Writing – original draft, Writing – review & editing

Affiliation School of Nursing, Duke University, Durham, North Carolina, United States of America

Roles Data curation, Writing – original draft, Writing – review & editing

Affiliation School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America

Roles Formal analysis, Writing – review & editing

Affiliation School of Nursing, The Johns Hopkins University, Baltimore, Maryland, United States of America

Roles Data curation, Writing – review & editing

Affiliation School of Nursing, Vanderbilt University, Nashville, Tennessee, United States of America

Affiliation Medstar Good Samaritan Hospital, Baltimore, Maryland, United States of America

Roles Data curation, Formal analysis, Writing – original draft, Writing – review & editing

  • Hae-Ra Han, 
  • Hailey N. Miller, 
  • Manka Nkimbeng, 
  • Chakra Budhathoki, 
  • Tanya Mikhael, 
  • Emerald Rivers, 
  • Ja’Lynn Gray, 
  • Kristen Trimble, 
  • Sotera Chow, 
  • Patty Wilson

PLOS

  • Published: June 22, 2021
  • https://doi.org/10.1371/journal.pone.0252747
  • Reader Comments

Fig 1

Health inequities remain a public health concern. Chronic adversity such as discrimination or racism as trauma may perpetuate health inequities in marginalized populations. There is a growing body of the literature on trauma informed and culturally competent care as essential elements of promoting health equity, yet no prior review has systematically addressed trauma informed interventions. The purpose of this study was to appraise the types, setting, scope, and delivery of trauma informed interventions and associated outcomes.

We performed database searches— PubMed, Embase, CINAHL, SCOPUS and PsycINFO—to identify quantitative studies published in English before June 2019. Thirty-two unique studies with one companion article met the eligibility criteria.

More than half of the 32 studies were randomized controlled trials (n = 19). Thirteen studies were conducted in the United States. Child abuse, domestic violence, or sexual assault were the most common types of trauma addressed (n = 16). While the interventions were largely focused on reducing symptoms of post-traumatic stress disorder (PTSD) (n = 23), depression (n = 16), or anxiety (n = 10), trauma informed interventions were mostly delivered in an outpatient setting (n = 20) by medical professionals (n = 21). Two most frequently used interventions were eye movement desensitization and reprocessing (n = 6) and cognitive behavioral therapy (n = 5). Intervention fidelity was addressed in 16 studies. Trauma informed interventions significantly reduced PTSD symptoms in 11 of 23 studies. Fifteen studies found improvements in three main psychological outcomes including PTSD symptoms (11 of 23), depression (9 of 16), and anxiety (5 of 10). Cognitive behavioral therapy consistently improved a wide range of outcomes including depression, anxiety, emotional dysregulation, interpersonal problems, and risky behaviors (n = 5).

Conclusions

There is inconsistent evidence to support trauma informed interventions as an effective approach for psychological outcomes. Future trauma informed intervention should be expanded in scope to address a wide range of trauma types such as racism and discrimination. Additionally, a wider range of trauma outcomes should be studied.

Citation: Han H-R, Miller HN, Nkimbeng M, Budhathoki C, Mikhael T, Rivers E, et al. (2021) Trauma informed interventions: A systematic review. PLoS ONE 16(6): e0252747. https://doi.org/10.1371/journal.pone.0252747

Editor: Vedat Sar, Koc University School of Medicine, TURKEY

Received: July 1, 2020; Accepted: May 23, 2021; Published: June 22, 2021

Copyright: © 2021 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: This is a systematic review. All relevant data were extracted from the published studies included in the review.

Funding: This study was supported, in part, by a grant from the Johns Hopkins Provost Discovery Award (HRH). Additional funding was received from the National Center for Advancing Translational Sciences (UL1TR003098, HRH), National Institute of Nursing Research (P30NR018093, HRH; T32NR012704, HM), National Institute on Aging (R01AG062649, HRH; F31AG057166, MN), Robert Wood Johnson Foundation Health Policy Research Scholar program (MN), and Substance Abuse and Mental Health Services Administration (5T06SM060559‐ 07, PW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.

Competing interests: The authors have declared that no competing interests exist.

Despite the United States’ commitment to health equity, health inequities remain a pressing concern among some of the nation’s marginalized populations, such as racial/ethnic or gender minority populations. For example, according to the 2016 National Health and Nutrition Examination Survey (NHANES), 29.1% of Mexican Americans and 24.3% of African Americans with diabetes had hemoglobin A1C greater than 9% (the gold standard of glucose control with levels ≤ 7% deemed adequate), compared to 11% in non-Hispanic whites [ 1 ]. The 2016 survey also revealed that 40.9% and 41.5% of Mexican Americans and African Americans with hypertension, respectively, had their blood pressure under control, compared to 51.7% in non-Hispanic whites. In 2014, 83% of all new diagnoses of HIV infection in the United States occurred among gay, bisexual, and other men who have sex with men, with African American men having the highest rates [ 2 ].

Several factors have been discussed as root causes of health inequities. For example, Farmer et al. [ 3 ] noted structural violence—the disadvantage and suffering that stems from the creation and perpetuation of structures, policies and institutional practices that are innately unjust—as a major determinant of health inequities. According to Farmer et al., because systemic exclusion and disadvantage are built into everyday social patterns and institutional processes, structural violence creates the conditions which sustain the proliferation of health and social inequities. For example, a recent analysis [ 4 ] using a sample including 4,515 National Health and Nutrition Examination Survey participants between 35 and 64 years of age revealed that black men and women had fewer years of education, were less likely to have health insurance, and had higher allostatic load (i.e., accumulation of physiological perturbations as a result of repeated or chronic stressors such as daily racial discrimination) compared to white men (2.5 vs 2.1, p <.01) and women (2.6 vs 1.9, p <.01). In the analysis, allostatic load burden was associated with higher cardiovascular and diabetes-related mortality among blacks, independent of socioeconomic status and health behaviors.

Browne et al. [ 5 ] identified essential elements of promoting health equity in marginalized populations such as trauma-informed and culturally competent care. In particular, trauma-informed care is increasingly getting closer attention and has been studied in a variety of contexts such as addiction treatment [ 6 – 8 ] and inpatient psychiatric care [ 9 ]. While there is a growing body of the literature on trauma-informed care, no prior review has systematically addressed trauma-informed interventions; one published review of literature [ 10 ] limited its scope to trauma survivors in physical healthcare settings. As such, the purpose of this paper is to conduct a systematic review and synthesize evidence on trauma-informed interventions.

For the purpose of this paper, we defined trauma as physical and psychological experiences that are distressing, emotionally painful, and stressful and can result from “an event, series of events, or set of circumstances” such as a natural disaster, physical or sexual abuse, or chronic adversity (e.g., discrimination, racism, oppression, poverty) [ 11 , 12 ]. We aim to: 1) describe the types, setting, scope, and delivery of trauma informed interventions and 2) evaluate the study findings on outcomes in association with trauma informed interventions in order to identify gaps and areas for future research.

Five electronic databases—PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), SCOPUS and PsycINFO—were searched from the inception of the databases to identify relevant quantitative studies published in English. The initial literature search was conducted in January 2018 and updated in June 2019 using the same search strategy.

Review design

We conducted a systematic review of quantitative evidence to evaluate the effects of trauma informed interventions. Due to heterogeneity relative to study outcomes, designs, and statistical analyses approaches among the included studies, we qualitatively synthesized the study findings. Three trained research assistants extracted study data. Specifically, we used the PICO framework to extract and organize key study information. The PICO framework offers a structure to address the following questions for study evidence [ 13 ]: Patient problem or population (i.e., patient characteristics or condition); Intervention (type of intervention tested or implemented); Comparison or control (comparison treatment or control condition, if any), and Outcome (effects resulting from the intervention).

Eligibility

Inclusion criteria..

Articles were screened for their relevance to the purpose of the review. Articles were included in this review if the study was: about trauma informed approach (i.e., an approach to address the needs of people who have experienced trauma) or an aspect of this approach, published in English language and involved participants who were 18 years and older. Also, only quantitative studies conducted within a primary care or community setting were included.

Exclusion criteria.

Exclusion criteria were: studies in or with military populations, refugee or war-related trauma populations, studies with mental health experts and clinicians as research subjects or studies of incarcerated and inpatient populations. Conference abstracts that had limited information on study characteristics were also excluded.

Search strategy and selection of studies

Search strategy..

Following consultation with a health science librarian, peer-reviewed articles were searched in PubMed, Embase, CINAHL, SCOPUS and PsycINFO using MeSH and Boolean search techniques. Search terms included: "trauma focused" OR "trauma-focused" OR "trauma informed" OR "trauma-informed." We also searched for the term trauma within three words of informed or focus ((trauma W/3 informed) OR (trauma W/3 focused), or (traumaN3 (focused OR informed)). Detailed search terms for each database are provided in Appendix 1.

Study selection.

The initial electronic search yielded 7,760 references and the follow-up search yielded 5,207 which were all imported into the Covidence software for screening [ 14 ]. Screening of the references was conducted by 2 independent reviewers and disagreements were resolved through consensus. There were 4,103 duplicates removed from the imported articles and 8,864 studies were forwarded to the title and abstract screening stage. Eight thousand five hundred and twenty-one studies were excluded because they were irrelevant. Three hundred and forty-three abstracts were identified to be read fully. Following this, 311 articles were excluded for focusing on other psychological conditions (n = 120), were non-experimental studies (n = 78) and were in inpatient or incarcerated populations (n = 46). One additional companion article was identified during full text review. Therefore, thirty-three articles met the inclusion criteria and are reported in this review. Fig 1 provides details of the selection process and identifies the reasons why articles were excluded at each stage.

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Quality assessment

We used the Joanna Briggs Institute quality appraisal tools [ 15 ] for randomized controlled trials (RCTs), quasi-experimental studies, and retrospective studies to assess the rigor of each study included in this review. The Joanna Briggs Institute quality appraisal tools [ 15 ] include items asking about methodological elements that are critical to the rigor of each type of study designs. In particular, one of the items for RCTs addresses participant blinding to treatment assignment. Due to the nature of trauma-informed interventions included in our review, it was decided that participant blinding is not relevant and hence was removed from the appraisal list for RCTs. No studies were excluded on the basis of the quality assessment. The quality assessment process was conducted independently by two raters. Inter-rater agreement rates ranged from 56% to 100% with the resulting statistic indicating substantial agreement (average inter-rater agreement rate = 77%). Discrepancies between raters were resolved via inter-rater discussion.

Overview of studies

Table 1 summarizes the main characteristics of the 32 unique studies included in the review, with one companion article [ 16 ] for a study which was later reported with a more thorough examination of findings [ 17 ] totaling 33 articles. More than half (n = 19) of the 32 studies were RCTs [ 17 – 35 ] whereas twelve studies were quasi-experimental [ 36 – 47 ] and one was retrospective study [ 48 ]. Thirteen studies were conducted in the U.S. [ 17 – 19 , 22 , 26 , 27 , 29 , 35 , 39 – 41 , 45 , 47 ]; five in the Netherlands [ 30 , 31 , 33 , 38 , 48 ]; three in Canada [ 23 , 25 , 46 ]; two in Australia [ 21 , 24 ]; two in the United Kingdom [ 36 , 44 ]; two in Sweden [ 42 , 43 ]; on study in Chile [ 20 ]; Iran [ 32 ]; Haiti [ 37 ]; South Africa [ 34 ]; and Germany [ 28 ]. Fourteen of the studies only included females in their sample [ 18 , 20 , 21 , 23 – 25 , 27 , 28 , 38 – 41 , 45 , 48 ]. The average sample size was 78 participants, with a range from 10 participants [ 38 ] to 297 participants [ 48 ]. Of the studies included, 67% had a sample size above 50 [ 18 – 22 , 26 , 29 – 34 , 36 , 37 , 39 – 42 , 46 – 48 ].

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The studies included in this review recruited their study populations largely based on the type of trauma they were aiming to address, such as individuals that experienced interpersonal traumatic event such as child abuse, sexual assault, or domestic violence [ 16 – 18 , 20 – 22 , 24 – 26 , 35 , 40 – 43 , 45 , 46 ], individuals with substance abuse disorders [ 19 , 47 , 48 ], couples experiencing clinically significant marital issues [ 23 ], individuals with limb amputations [ 38 ], dental phobia [ 28 ], or fire service personnel suffering from post-traumatic stress disorder [ 44 ]. Trauma was self-reported in eight articles [ 16 , 17 , 20 , 22 , 26 , 34 , 35 , 47 ]. In contrast, nine studies clearly identified a measurement of trauma; the Trauma History Questionnaire [ 19 , 45 ], the Childhood Trauma Questionnaire [ 23 , 25 ], the Childhood Maltreatment Interview Schedule [ 23 ], the Revised Conflict Tactics Scale adapted for sex work [ 39 ], the Traumatic Events Screening Instrument for Adults [ 27 ], the Life Events Checklist [ 46 ], and the Adverse Childhood Experiences [ 18 ]. Two studies used a clinical tool (e.g. eye movement desensitization and reprocessing [ 38 ] and Diagnostic and Statistical Manual of Mental Disorders, 4 th edition [ 41 ] to identify or diagnose trauma. Fifteen studies did not include direct measurements for trauma [ 21 , 24 , 28 – 33 , 36 , 37 , 40 , 42 – 44 , 48 ].

Quality ratings

Tables 2 – 4 shows final scores of quality assessment. Quality of the 32 unique studies included in this review varied across individual studies. Twelve of 19 RCTs included in the review were of high quality (i.e., 9 to 11) [ 17 , 18 , 20 , 21 , 24 , 26 , 28 , 29 , 31 , 33 – 35 ] and six were of medium quality (i.e., 5 to 8) [ 19 , 22 , 23 , 25 , 27 , 30 ]. One study scored 4 of 12 [ 32 ]. The low rating study [ 32 ] lacked relevant information to adequately score its methodological rigor. Most RCTs clearly described randomization, group equivalence at baseline, rates and reasons for attrition, study outcomes, and analysis. Blinding of outcomes assessors to treatment assignment was used and described in several RCTs [ 17 , 20 , 21 , 24 , 27 , 35 ], whereas blinding of those delivering treatment was discussed clearly in only one study [ 25 ]. The majority of the quasi-experimental studies were of high quality (i.e., 7 or higher), except two, which scored 2 of 9 [ 37 ] and 6 of 9 [ 39 ], respectively. Six of twelve quasi-experimental studies [ 36 , 41 – 44 , 47 ] had a comparison group to strengthen internal validity of causal inferences by comparing intervention and control groups. Some of these studies, however, noted differences in baseline assessments between groups [ 36 , 43 , 44 ]. Finally, one retrospective study [ 48 ] scored 11 of 11 and hence was rated as high quality.

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Characteristics of trauma-informed interventions

Type of intervention..

Table 5 details the trauma informed intervention characteristics included in this review. The two most frequently used interventions were eye movement desensitization and reprocessing (EMDR) [ 28 , 30 , 31 , 33 , 36 , 38 ]—a multi-phase intervention using bilateral stimulation, such as left-to-right eyes movements or hand tapping, to desensitize individuals to a traumatic memory or image—and trauma-focused cognitive behavioral therapy or cognitive behavioral therapy (CBT) [ 26 , 27 , 32 , 46 , 48 ]—a psychological approach to introduce emotional regulation and coping strategies (e.g., deep muscle relaxation, yoga, thought discovery and breathing techniques) to deal with negative feelings and behaviors surrounding a trauma of interest [ 32 , 48 ]. The implementation of CBT varied on the trauma of interest. Other studies implemented interventions using general trauma focused therapy [ 22 , 43 ], emotion focused therapy [ 23 , 25 ], stress reduction programs [ 17 ], cognitive processing therapy [ 24 ], brief electric psychotherapy [ 31 ], present focused group therapy [ 26 ], compassion focused therapy [ 44 ], prolonged exposure [ 45 ], stress inoculation training [ 45 ], psychodynamic therapy [ 45 ], and visual schema displacement therapy [ 30 ]. A number of studies included more than one of these therapies [ 13 , 26 , 30 , 31 , 33 , 36 , 45 ].

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Setting, scope, and delivery of intervention.

Twenty of the interventions were identified to occur in an outpatient clinic/setting [ 19 – 21 , 24 , 25 , 27 – 29 , 31 – 34 , 36 , 39 , 40 , 42 , 43 , 46 – 48 ]. Four of the studies took place in a research lab or office [ 23 , 26 , 41 , 45 ], one study occurred in the community [ 17 ], and one study implemented therapy in three locations, two of which were outpatient and one of which was a residential treatment center [ 47 ]. Lastly, one study occurred in internally displaced people’s camps within a metropolitan area in Haiti [ 37 ]. The remaining studies did not identify a specific setting [ 22 , 35 , 38 , 44 ].

The interventions ranged in length and time, but most often occurred weekly. The longest intervention was done by Lundqvist and colleagues [ 43 ], which lasted a total length of 2-years and included 46 sessions. Several other studies included 20 sessions or more [ 18 , 22 , 23 , 25 , 26 ]. The interventions were most commonly delivered by medical professionals, including but not limited to: psychologists or psychiatrists, therapists, social workers, mental health clinicians and physicians [ 16 , 17 , 20 – 29 , 33 , 36 , 38 , 39 , 41 , 44 – 47 ]. The articles frequently noted that the interventionists were masters-level-prepared or higher in their profession [ 21 , 23 , 25 – 27 , 33 , 40 , 47 ]. In addition to standard education and licensure, many of the professionals implementing the interventions were required to obtain further training in the therapy of interest [ 23 – 25 , 27 – 30 , 33 , 36 , 38 – 40 , 46 , 47 ]. Two studies were identified to be delivered by lay persons [ 34 , 37 ].

Fidelity was addressed in 16 of the included articles [ 16 , 19 , 21 , 23 , 24 , 26 – 30 , 33 – 35 , 45 – 47 ]. The manner in which fidelity was addressed varied by study. Videotaping or audiotaping therapy sessions [ 21 , 23 , 24 , 28 – 30 , 33 , 35 ] were most common, followed by deploying regular supervision of the therapy sessions [ 21 , 23 , 27 , 29 , 33 , 46 ], using a training manual or intervention protocols [ 19 , 21 , 33 , 46 ], or having individuals unaffiliated with the study or blind to the intervention rate sessions [ 21 , 26 , 28 , 35 ]. Additionally, three articles utilized fidelity checks/checklists to ensure components of the intervention were addressed [ 16 , 30 , 47 ] or had patients and/or therapists rate therapy sessions [ 26 , 34 , 45 ]. Finally, one study had quality assurance worksheets completed after each session that were later reviewed by the study coordinator [ 34 ].

Effects of trauma-informed interventions

Trauma-informed interventions were tested to improve several psychological outcomes, such as post-traumatic stress disorder (PTSD), depression, and anxiety. The most frequently assessed psychological outcome was PTSD, which was examined in 23 out of the 32 studies [ 17 , 20 – 27 , 31 , 33 , 35 – 39 , 41 , 42 , 44 – 48 ]. Among the studies that assessed PTSD as an outcome, 11 found significant reductions in PTSD symptoms and severity following the trauma-informed intervention [ 17 , 20 , 21 , 24 , 26 , 28 , 34 , 42 , 45 – 47 ], however, one of these studies, which utilized outpatient psychoeducation, did not find significant differences in reduction between the intervention and control group [ 20 ]. Trauma-informed interventions that were associated with a significant reduction in PTSD were a mindfulness-based stress reduction program [ 16 ], two therapies using the Trauma Recovery and Empowerment Model (TREM) [ 47 ], CBT [ 26 , 46 ], EMDR [ 28 ], general trauma-focused therapy [ 42 ], psychodynamic therapy [ 45 ], stress inoculation therapy [ 45 ], present-focused therapy [ 26 ], and cognitive processing therapy [ 24 ]. In addition, an intervention designed to reduce stress and improve HIV care engagement improved PTSD symptoms; however, this intervention was not intended to treat PTSD [ 34 ].

Other commonly assessed psychological symptoms, including depression and anxiety, were examined in 16 [ 17 – 21 , 24 – 26 , 29 , 31 , 32 , 35 , 40 , 44 , 47 , 48 ] and 10 [ 21 , 24 , 25 , 28 , 29 , 35 , 36 , 44 , 47 , 48 ] studies, respectively. Among these, trauma-informed interventions were associated with decreased or improved depressive symptoms in 9 studies [ 17 , 18 , 20 , 21 , 24 , 32 , 35 , 47 , 48 ] and decreased or improved anxiety in 5 studies [ 21 , 28 , 35 , 47 , 48 ]. For example, Vitriol and colleagues found that outpatient psychoeducation resulted in improved depressive symptoms in women with severe depression and childhood trauma [ 20 ]. Similarly, Kelly and colleagues found that female survivors of interpersonal violence experienced a significantly greater reduction of depressive symptoms in the intervention group (mindfulness-based stress reduction) compared to the control group [ 16 , 17 ]. Other therapies that resulted in improved depressive symptoms were TREM [ 47 ], prolonged exposure therapy [ 21 ], CBT [ 32 , 46 ], psychoeducational cognitive restructuring [ 35 ], and financial empowerment education [ 18 ]. Cognitive processing therapy similarly resulted in large reductions in depression symptoms, however this reduction was also observed in the control group [ 24 ]. The same studies showed that TREM [ 47 ], prolonged exposure therapy [ 21 ], CBT [ 48 ], and psychoeducational cognitive restructuring [ 35 ] were associated with improved anxiety. Lastly, in a separate study than the one highlighted above, EMDR was associated with improved anxiety [ 28 ].

A select number of the studies found associations between trauma-informed interventions and other psychological outcomes such as attachment anxiety, attachment avoidance, psychiatric symptoms or dental distress. For example, the trauma-informed mindfulness-based reduction program implemented by Kelly and colleagues was associated with a greater decrease in anxious attachment, measured by the Relationship Structures Questionnaire, compared to the waitlist group [ 17 ]. Similarly, Masin-Moyer and colleagues found that TREM and an attachment-informed TREM (ATREM) were associated with significant reductions in group attachment anxiety, group attachment avoidance, and psychological distress in women with a history of interpersonal trauma [ 47 ]. Additionally, individuals in an outpatient substance abuse treatment program, consisting of psychoeducational seminars and trauma-informed addiction treatment, experienced significantly better outcomes of psychiatric severity, measured by the Global Appraisal of Individual Needs scale, compared to a control treatment group [ 19 ]. Doering and colleagues found that EMDR, compared to the control group, was associated with significantly greater improvement in dental stress, anxiety and fear in patients with dental-phobia [ 28 ].

There was a series of interpersonal, emotional and behavioral outcomes assessed in the included studies. For example, adult females that were sexually abused in childhood experienced a significant improvement in social interaction and social adjustment after receiving trauma focused group therapy [ 43 ]. Similarly, Dalton and colleagues found that couples that received emotion focused therapy experienced a significant reduction in relationship distress [ 23 ] and MacIntosh and colleagues found that individuals that received CBT reported lower interpersonal problems post-treatment [ 46 ]. Trauma-based interventions were also associated with emotional outcomes. Visual schema displacement therapy and EMDR both were superior to the control treatment in reducing emotional disturbance and vividness of negative memories [ 30 ]. In a separate study, CBT was found to reduce levels of emotional dysregulation in individuals that experienced childhood sexual abuse [ 46 ]. Lastly, trauma-informed interventions were associated with behavioral outcomes, including HIV risk reduction [ 26 ], decreased days of alcohol use [ 27 ], and improvements in avoidance of client condom negotiations, frequency of sex trade under influence of drugs or alcohol, and use of intimate partner violence support [ 40 ]. Interventions that were associated with these behavioral outcomes included trauma focused and present focused group therapy [ 26 ], CBT [ 27 ], and a trauma-informed support, validation, and safety-promotion dialogue intervention [ 40 ].

Publication bias

We analyzed three sets of outcome variables for publication bias: PTSD, depression, and anxiety. Based on Begg and Mazumdar test, there was no evidence of publication bias for PTSD (z = 1.55, p = 0.121) and anxiety (z = 0.29, p = 0.769). However, there was some evidence of publication bias for depression (z = 5.19, p<.001). The statistically significant publication bias for depression appears to be mainly due to large effect sizes in Nixon [ 24 ] and Bowland [ 35 ].

According to our database search, this is the first systematic review to critically appraise trauma-informed interventions using a comprehensive definition of trauma. In particular, our definition encompassed both physical and psychological experiences resulting from various circumstances including chronic adversity. Overall, there was inconsistent evidence to suggest trauma informed interventions in addressing psychological outcomes. We found that trauma-informed interventions were effective in improving PTSD [ 17 , 20 , 21 , 24 , 26 , 28 , 34 , 42 , 45 – 47 ] and anxiety [ 21 , 28 , 35 , 47 , 48 ] in less than half of the studies where these outcomes were included. We also found that depression was improved in less than about two thirds of the studies where the outcome was included [ 17 , 18 , 20 , 21 , 24 , 32 , 35 , 47 , 48 ]. Although limited in the number of published studies included this review, available evidence consistently supported trauma-informed interventions in addressing interpersonal [ 23 , 43 , 46 ], emotional [ 30 , 46 ], and behavioral outcomes [ 26 , 27 , 40 ].

Effective trauma informed intervention models used in the studies varied, encompassing CBT, EMDR, or other cognitively oriented approaches such as mindfulness exercises [ 16 , 24 , 26 , 28 , 32 , 35 , 45 , 46 , 48 ]. In particular, CBT was noted as an effective trauma informed intervention strategy which successfully led to improvements in a wide range of outcomes such as depression [ 32 , 48 ], anxiety [ 48 ], emotional dysregulation [ 46 ], interpersonal problems [ 23 , 46 ], and risky behaviors (e.g., days of alcohol use) [ 27 ]. While the majority of the studies included in the review were focused on interpersonal trauma such as child abuse, sexual assault, or domestic violence [ 16 – 18 , 20 – 22 , 24 – 26 , 35 , 40 – 43 , 45 , 46 ], growing evidence demonstrates perceived discrimination and racism as significant psychological trauma and as underlying factors in inflammatory-based chronic diseases such as cardiovascular disease or diabetes [ 4 ]. Future trauma informed interventions should consider a wide-spectrum of trauma types, such as racism and discrimination, by which racial/ethnic minorities are disproportionately affected from [ 49 ].

While the majority of the trauma informed interventions were delivered by specialized medical professionals trained in the therapy [ 16 , 17 , 20 – 29 , 33 , 36 , 38 – 41 , 44 – 47 ], several of the articles lacked full descriptions of interventionist training and fidelity monitoring [ 20 , 22 , 25 , 36 , 38 – 41 , 44 ]. Two studies were identified to be delivered by lay persons [ 34 , 37 ]. There is sufficient evidence to suggest that lay persons, upon training, can successfully cover a wide scope of work and produce the full impact of community-based intervention approaches [ 50 ]. Given such, there is a strong need for trauma informed intervention studies to clearly elaborate the contents and processes of lay person training such as competency evaluation and supervision to optimize the use of this approach.

There are methodological issues to be taken into consideration when interpreting the findings in this review. While twenty-three of 32 studies were of high quality [ 17 , 18 , 20 , 21 , 24 , 26 , 28 , 29 , 31 , 33 – 36 , 38 , 40 – 48 ], some studies lacked methodological rigor, which might have led to false negative results (no effects of trauma informed interventions). For example, about one-third (31%) had a sample size less than 50 [ 17 , 23 – 25 , 27 , 28 , 35 , 38 , 43 , 45 ]. In addition, half of the quasi-experimental studies [ 37 – 40 , 45 , 46 ] did not have a comparison group or when they had one, group differences were noted in baseline assessments [ 36 , 43 , 44 ]. In several studies, therapists took on both traditional treatment and research responsibilities (e.g., delivery of the intervention) [ 20 , 25 , 29 , 32 , 33 , 36 , 40 , 46 , 47 ], yet blinding of those delivering treatment was discussed clearly in only one study [ 25 ]. This dual role is likely to have led to the disclosure of group allocation, hence, threatening the internal validity of the results. Future studies should address these issues by calculating proper sample size a priori, using a comparison group, and concealing group assignments.

Review limitations

Several limitations of this review should be noted. First, by using narrowly defined search terms, it is possible that we did not extract all relevant articles in the existing literature. However, to avoid this, we conducted a systematic electronic search using a comprehensive list of MeSH terms, as well as similar keywords, with consultation from an experienced health science librarian. Additionally, we hand searched our reference collections, Second, the trauma informed interventions included in this review were implemented to predominantly address trauma related to sexual or physical abuse among women. Thus, our findings may not be applicable to trauma related to other types of incidence such as chronic adversity (e.g., racism or discrimination). Likewise, there were insufficient studies addressing a wider range of trauma impacts such as emotion regulation, dissociation, revictimization, non-suicidal self-injury or suicidal attempts, or post-traumatic growth. Future research is warranted to address these broader impacts of trauma. We included only articles written in English; therefore, we limited the generalizability of the findings concerning studies published in non-English languages. Finally, we used arbitrary cutoff scores to categorize studies as low, medium, and high quality (quality ratings of 0-4, 5-8, and 9+ for RCTs and 0-3, 4-6, 7+ for quasi-experimental studies, respectively). Using this approach, each quality-rating item was equally weighted. However, certain factors (e.g., randomization method) may contribute to the study quality more so than others.

Our review of 33 articles shows that there is inconsistent evidence to support trauma informed interventions as an effective intervention approach for psychological outcomes (e.g., PTSD, depression, and anxiety). With growing evidence in health disparities, adopting trauma informed approaches is a growing trend. Our findings suggest the need for more rigorous and continued evaluations of the trauma informed intervention approach and for a wide range of trauma types and populations.

Supporting information

S1 checklist..

https://doi.org/10.1371/journal.pone.0252747.s001

S1 Appendix. Search strategies.

https://doi.org/10.1371/journal.pone.0252747.s002

Acknowledgments

We would like to express our appreciation to a medical librarian, Stella Seal for her assistance with article search. Both Kristen Trimble and Sotera Chow were students in the Masters Entry into Nursing program and Hailey Miller and Manka Nkimbeng were pre-doctoral fellows at The Johns Hopkins University when this work was initiated.

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  • Published: 16 July 2020

Exploring the impact of trauma type and extent of exposure on posttraumatic alterations in 5-HT1A expression

  • Michael W. Lewis   ORCID: orcid.org/0000-0002-3903-9055 1 ,
  • Russell T. Jones 1   na1 &
  • Margaret T. Davis   ORCID: orcid.org/0000-0001-7297-710X 2   na1  

Translational Psychiatry volume  10 , Article number:  237 ( 2020 ) Cite this article

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  • Molecular neuroscience
  • Pathogenesis

The long-term behavioral, psychological, and neurobiological effects of exposure to potentially traumatic events vary within the human population. Studies conducted on trauma-exposed human subjects suggest that differences in trauma type and extent of exposure combine to affect development, maintenance, and treatment of a variety of psychiatric syndromes. The serotonin 1-A receptor (5-HT1A) is an inhibitory G protein-coupled serotonin receptor encoded by the HTR1A gene that plays a role in regulating serotonin release, physiological stress responding, and emotional behavior. Studies from the preclinical and human literature suggest that dysfunctional expression of 5-HT1A is associated with a multitude of psychiatric symptoms commonly seen in trauma-exposed individuals. Here, we synthesize the literature, including numerous preclinical studies, examining differences in alterations in 5-HT1A expression following trauma exposure. Collectively, these findings suggest that the impact of trauma exposure on 5-HT1A expression is dependent, in part, on trauma type and extent of exposure. Furthermore, preclinical and human studies suggest that this observation likely applies to additional molecular targets and may help explain variation in trauma-induced changes in behavior and treatment responsivity. In order to understand the neurobiological impact of trauma, including the impact on 5-HT1A expression, it is crucial to consider both trauma type and extent of exposure.

Introduction

Exposure to potentially traumatic events is common, with an estimated rate of over 80% in the United States and 70% worldwide 1 . However, long-term behavioral, psychological, and neurobiological effects of exposure vary considerably 2 . Some individuals experience rapid and sustained natural recovery, while others develop chronic trauma-related psychopathology 3 . Importantly, the nature and extent of trauma exposure combine to produce different outcomes; research suggests that exposure to qualitatively different events and different degrees of exposure lead to different psychiatric and neurobiological outcomes 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 . For example, qualitatively different events (e.g., rape, assault, and natural disaster) are associated with different levels of conditional risk for posttraumatic stress disorder (PTSD; 19% rape and 0.3% natural disaster) 20 . Similarly, different trauma types are differentially correlated with the emergence of several other psychiatric diagnoses and sequalae following trauma exposure (e.g., depression, anxiety, substance abuse, conduct problems, eating disorders, suicidal ideation, and psychosis) 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 . Furthermore, research suggests that genetic risk for PTSD covaries with trauma type, timing, severity, and degree of exposure 22 , 23 , 24 , 25 , 26 , 27 , 28 . Critically, research suggests that the dissociative subtype of PTSD and informally recognized subtypes of major depressive disorder (MDD; e.g., anxious depression, and psychotic subtype) may develop as a result of childhood trauma history, are characterized by distinct neurobiological mechanisms, and require different treatment approaches 29 , 30 , 31 , 32 , 33 , 34 . This suggests that common neurobiological factors among trauma-exposed individuals may contribute to heterogeneity in psychiatric symptoms and treatment responsivity; neurobiological phenotypes of trauma-induced psychiatric dysfunction transcend traditional diagnostic categories. In order to understand observed variability in the long-term effects of trauma exposure, it may be necessary to examine the relationship between variability in the nature and extent of trauma exposure and associated trauma-induced neurobiological alterations.

Research suggests that individual differences in the expression and activity of serotonin 1-A receptor (5-HT1A) are associated with a multitude of psychiatric symptoms commonly seen in trauma-exposed individuals 35 , 36 , 37 , 38 , 39 , 40 . Previous reviews have synthesized literature related to the role of 5-HT1A in depression, anxiety, memory, fear learning, impulsivity, suicide, and social dysfunction 35 , 36 , 37 , 38 , 39 , 40 . In addition, a multitude of preclinical studies have examined trauma-induced alterations in 5-HT1A 41 . Though the preclinical literature is consistent in suggesting that trauma alters 5-HT1A expression, specific findings diverge; some studies have observed increasing expression 41 , while others have observed the opposite 42 . In addition, many studies have presented conflicting evidence regarding specific brain regions in which increases and decreases occur 41 , 42 , 43 . Here, we synthesize the literature, including numerous preclinical studies, examining differences in alterations in 5-HT1A expression following trauma exposure. We suggest that observed inconsistencies may be accounted for in part by the influence of differences in the type of trauma subjects are exposed to. Furthermore, we suggest that the same is likely true of other molecular targets and that consideration of trauma type is a key aspect of accurate data interpretation. Thus, we examine the literature on 5-HT1A as an exemplar of a more general observation: in order to understand the neurobiology of trauma, one must account for covariance of trauma type and neurobiological alterations.

The 5-HT1A receptor is one of seven inhibitory G protein-coupled serotonin receptors and is encoded by the HTR1A gene 44 . It is found in high density in areas associated with serotonin release (raphe nuclei), memory (hippocampus), fear (amygdala), pleasure (septum), and higher-order cognition (cerebral cortex) 38 , 45 , 46 , 47 , 48 , 49 , 50 , 51 . Physiologically, 5-HT1A activity in areas of high density as well as in several areas of lower density regulates neurotransmitter (e.g., dopamine, acetylcholine, noradrenaline, GABA, and glutamate) and hormone (e.g., cortisol and oxytocin) release as well as neural activity and functional connectivity 52 , 53 , 54 , 55 , 56 , 57 , 58 . In addition, 5-HT1A activity has been shown to modulate a wide array of adaptive and maladaptive behaviors. For example, in rodents, the 5-HT1A agonist 8-OH-DPAT has been found to increase impulsive action at low doses, and decrease impulsive action at higher doses 59 . Moreover, both agonists and antagonists of 5-HT1A have been shown to have antidepressant effects in preclinical models 60 , 61 . The region-specific nature of the physiological effects of 5-HT1A may be relevant to its impact on adaptive and maladaptive behaviors.

Among trauma-exposed individuals, numerous human studies have identified social behaviors as key differentiating factors which separate resilience from vulnerability (e.g., Refs. 62 , 63 ). Though it is generally accepted that 5-HT1A exerts strong effects on social behavior, those effects are highly complex 64 , 65 . For example, one study found that the 5-HT1A full agonist 8-OH-DPAT, the 5-HT1A partial agonist ipsapirone, and the region-specific partial agonist of 5-HT1A autoreceptors/antagonist of 5-HT1A heteroreceptors MDL-73,005-EF each led to a distinct pattern of effects on social behavior in rodents 64 . Regarding the overall frequency of pro-social behavior, 8-OH-DPAT led to an increase, MDL-73,005-EF led to a decrease, and ipsapirone had no effect 64 . In addition to the overall effects, each of the three drugs led to a specific combination of increases and decreases in each of six specific pro-social behaviors, six specific aggressive behaviors, and five specific defensive behaviors 64 . In addition, one study found that treating female marmoset monkeys with the 5-HT1A agonist 8-OH-DPAT impaired pair bond quality and decreased female sexual behavior 66 . By contrast, flibanserin, a regionally selective postsynaptic 5-HT1A heteroreceptors agonist/5-HT2A antagonist, improved pair bond quality and increased female sexual behavior 66 . Studies such as these have demonstrated the ability of different types of alterations in 5-HT1A activity (as well as its interactions with other receptors) to affect behaviors (both adaptive and maladaptive) shown to develop in the wake of trauma exposure.

In addition to social functioning, 5-HT1A modulates numerous trauma-relevant behaviors. A multitude of preclinical and human studies have linked 5-HT1A expression and activation to a number of well-known trauma sequalae; examples include depression (for reviews, see Refs. 35 , 44 , 67 , 68 ), anxiety (for reviews, see Refs. 36 , 68 ), memory (for reviews, see Refs. 38 , 69 , 70 , 71 ), fear learning (for review, see Ref. 37 ), impulsivity (for review, see Ref. 39 ), suicide (for review, see Ref. 40 ), substance abuse (e.g., Ref. 72 ), social dysfunction (for review, see Ref. 64 ), and pharmacological treatment responsivity (for reviews, see Refs. 73 , 74 ). Given the variety of trauma-related behaviors and neurobiological substrates that 5-HT1A receptors modulate, it is reasonable to hypothesize that heterogeneity in trauma-induced 5-HT1A alterations contributes to heterogeneity in psychiatric symptom expression. However, while numerous reviews discuss the impact of 5-HT1A on behaviors which are implicated in trauma, no works of which we are aware have synthesized the literature regarding trauma’s impact on 5-HT1A.

We argue that the importance of synthesizing the literature regarding the relationship between trauma exposure and 5-HT1A expression is that 5-HT1A can act as an exemplar of a general principle: that trauma type, chronicity, and duration likely have an impact on many (and possibly all) trauma-induced molecular alterations. Many of the fundamental mechanisms through which stress alters gene expression in general (e.g., transcription factors, miRNA, etc.) and 5-HT1A expression specifically (e.g., Freud-1 and miR-135a) regulate the expression of multiple genes rather than just one particular gene 44 . Thus, it is unlikely that different types of trauma or degrees of exposure would differentially impact the expression of one gene but not others. Though any number of molecular targets could theoretically be used to demonstrate this principle, 5-HT1A was used in this article for both practical and theory-driven reasons.

Our justification for selecting 5-HT1A as an exemplar here is twofold. First, because 5-HT1A is among the most widely studied molecular mechanisms of stressor-related psychopathology, a robust 5-HT1A focused preclinical literature exists 44 . This is critical because examination of the importance of trauma type and extent of exposure requires comparison of studies for which all other methodologies overlap; only a small portion of the literature meets all of those criteria. Second, by focusing on a molecular target that is widely studied in relation to stressor-related disorders but not often studied in relation to trauma, this work aims to call attention to a possible gap in the literature. In addition to PTSD, we believe that this work has the potential to inform the literature on depression, anxiety, and many other psychiatric diagnoses linked with 5-HT1A dysfunction.

5-HT1A and trauma: human studies

To date, very few published studies have directly examined the association between trauma exposure and 5-HT1A expression in humans. In addition, none have accounted for trauma type. However, a recent positron emission tomography (PET) study observed a negative correlation between chronic psychosocial stress and 5-HT1A availability in vivo in the hippocampus, anterior cingulate cortex, and insular cortex in humans 75 . Furthermore, using PET, subjects with PTSD have been found to have elevated 5-HT1A availability across 13 brain regions 76 . Notably, the results of some PET studies have been shown to vary as a function of which outcome measure researchers employ. For example, when researchers examining the relationship between PTSD and 5-HT1A availability used binding potential nondisplaceable uptake (BP ND ; the outcome measure employed in the psychosocial stress study) rather than binding potential free plasma concentration (BP F ), no relationship between PTSD and 5-HT1A was observed 76 , 77 . Another issue that limits interpretation of these findings is the cross-sectional nature of the study designs. Without longitudinal data it is not possible to determine whether dysregulated 5-HT1A expression occurred as a result of stress exposure (traumatic or otherwise) or represents a preexisting risk factor for stressor-induced disorders. For example, elevated 5-HT1A availability has been observed in subjects with remitted MDD and has been found to be a heritable preexisting risk factor for MDD 78 , 79 . While no published human studies have used longitudinal designs to study the effect of trauma on 5-HT1A expression, a body of preclinical literature suggests that trauma exposure may alter 5-HT1A expression.

Preclinical models of traumatic stress exposure

In both humans and rodents, the line between non-trauma stress exposure and traumatic stress exposure is often blurry and imprecisely defined. In fact, the “Diagnostic and Statistical Manual” (DSM) definition of trauma exposure has been altered multiple times 80 . Though each DSM has presented a binary definition of PTE exposure, it is unclear whether the present dichotomous approach is adequate 80 . As mentioned previously, qualitatively different types of traumas can produce distinct neurobiological and behavioral consequences (e.g., Ref. 21 ). In addition, while the DSM uses a binary approach to define the boundary between “stress” and “trauma,” it may be important to focus more on qualitative aspects of distinct types of intense stressors and less on a dichotomous variable. For example, both criterion-A-type and noncriterion-A-type childhood maltreatment have been found to be negatively correlated with fractional anisotropy in the inferior longitudinal fasciculus 81 . Controversies regarding the use of a binary definition of trauma, which may incorrectly exclude some extreme stressors while incorrectly amalgamating others, have led to calls for a more fine-grained approach 80 .

The ambiguous and heterogeneous nature of PTEs is reflected in the preclinical trauma literature. A number of different preclinical models have been used to study trauma, including single prolonged stress (SPS), predator threat, restraint stress (RS; aka immobilization stress), inescapable electric shock (IES), fear conditioning (FC), chronic unpredictable stress (CUS; aka chronic variable stress), chronic social defeat (CSD), maternal separation (MS), and MS unpredictable stress. These paradigms and their relationship with trauma have been described and reviewed elsewhere (e.g., Refs. 53 , 82 , 83 , 84 , 85 ). Of note, CUS is an umbrella term encompassing any paradigm which involves daily exposure to one or more different stressors in a randomized sequence for 1 week or longer 86 . In this work, we only include CUS paradigms that include exposure to at least one of the aforementioned acute traumatic stressors. Just as many of the DSM-defined criterion A traumas were not included in the original definition of trauma exposure 80 , most of these preclinical trauma models were not initially conceptualized as representing trauma (e.g., RS, IES, FC, CUS, CSD, and MS) 82 , 83 . Due to the multifaceted and heterogeneous nature of potentially traumatic events, previous reviews have stated that no single preclinical model of trauma can adequately capture all aspects of trauma and that an ideal approach should draw from a variety of distinct models 82 , 83 .

While not traditionally viewed as a trauma paradigm, forced swim (FS) has been described as an uncontrollable and anxiogenic life-threatening situation 87 and has been used in several studies to model trauma-related abnormalities in neurobiology, memory, and pain 88 , 89 , 90 . The behavioral effects of both acute and chronic FS stress have been measured using a number of additional preclinical tests (e.g., sucrose preference test, tail suspension test, elevated plus maze, open field test, social exploration test, Morris water maze, object location test, prepulse inhibition, cocaine preference, ethanol preference) (e.g., Refs. 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 ). Based on those tests, numerous studies have found evidence that FS can induce preclinical dysfunctions reflective of trauma sequalae including anhedonia (e.g., Ref. 92 ), anxiety (e.g., Ref. 110 ), social anxiety (e.g., Ref. 100 ), cognitive dysfunction (e.g., Ref. 108 ), depression (e.g., Ref. 93 ), and substance abuse (e.g., Ref. 109 ). Based on the intense nature of the stressor and its capacity for causing behavioral dysfunctions reflective of multiple facets of trauma-induced psychopathology, FS may represent an additional model of potentially traumatic event exposure. Thus, in order to provide a comprehensive picture of covariance of trauma type and 5-HT1A alterations, FS is included in this review.

Importantly, preclinical trauma models vary qualitatively in ways that make them appropriate analogs of different types of traumatic event exposure. In humans, interpersonal traumas (e.g., physical assault, sexual assault, and family violence) are qualitatively different from non-interpersonal traumas (e.g., severe accident, natural disaster, and life-threatening illness); this contributes to differences in psychiatric symptom severity and outcomes 111 , 112 . Similarly, some preclinical models incorporate a clear social component (e.g., CSD and MS), while others lack a social component (e.g., FC and RS) 83 . Additional clinically relevant qualitative factors which vary among preclinical trauma models include degree of threat of bodily harm, actual physical pain inflicted, and predictability 83 . In addition to qualitative differences, preclinical trauma models can vary in duration (time per exposure) and chronicity (days of exposure) 83 . In humans, increases in both duration and chronicity of trauma exposure, or number of lifetime exposures to trauma increase subjective peri-traumatic suffering and have been linked to increased symptom severity and qualitatively different psychiatric outcomes 112 , 113 , 114 , 115 , 116 , 117 , 118 . Evidence suggests that both qualitative and quantitative differences in rodent trauma models contribute to differences in their impact on rodent behavior and neurobiology 83 . Thus, differences in neurobiological response to various preclinical models of trauma may provide insight into the role of trauma type, duration, and chronicity in contributing to neurobiological heterogeneity among individuals with psychiatric disorders.

Types of traumatic stress exposure and 5-HT1A alterations

As discussed above, different preclinical paradigms can be seen as analogs of distinct types of traumatic events; preclinical results suggest that when controlling for all other factors, exposure to qualitatively different traumatic events (preclinical paradigms) differentially affects alterations in 5-HT1A mRNA expression. For example, preclinical studies have found that exposure to CUS (approximates chronic exposure to various unpredictable and uncontrollable traumas) led to a decrease in 5-HT1A mRNA expression in all hippocampal subfields compared to controls, but exposure to SPS (approximates single exposure to prolonged perceived life threat) led to a decrease in hippocampal 5-HT1A mRNA expression that was restricted to the CA1 and dentate gyrus 42 , 119 . In one study, chronic exposure to 20 min of FS (approximates chronic and predictable exposure to perceived threat of drowning) did not alter 5-HT1A mRNA expression in any hippocampal region 119 . Comparison of these findings reveals that animals exposed to different preclinical paradigms, and thus qualitatively different traumatic events, experienced substantially different alterations in 5-HT1A mRNA expression; trauma-induced alterations in hippocampal 5-HT1A mRNA expression may be affected by both quality and frequency of trauma exposure.

Though alterations in mRNA expression represent transcriptional alterations in gene expression, posttranscriptional mechanisms may also cause changes in gene expression, especially during dynamic processes such as those which occur after trauma exposure 120 . Posttranscriptional mechanisms include any process after the transcription of DNA into mRNA, which affect subsequent steps of gene expression 120 . Exposure to SPS, CF + SPS (SPS preceded by five days of FC), or CUS have led to concurrent increases in 5-HT1A mRNA expression and 5-HT1A expression 41 , 119 , 120 , 121 , 122 . The concurrent nature of these changes in 5-HT1A mRNA and 5-HT1A protein expression suggests that transcriptional mechanisms are at least partially responsible for the observed change in 5-HT1A expression in these studies. However, two studies found that exposure to RS (approximates prolonged and uncontrollable confinement and threat of bodily harm) or FS (approximates perceived threat of drowning) led to incongruities in 5-HT1A mRNA expression and 5-HT1A expression 123 , 124 . For example, one study found that exposure to chronic RS led to an increase in 5-HT1A mRNA expression, but a decrease in 5-HT1A expression in the prefrontal cortex 123 . The opposing direction of alterations in 5-HT1A mRNA expression and 5-HT1A expression suggests that posttranscriptional mechanisms led to the decrease in 5-HT1A expression. Furthermore, when controlling for all other factors, one study found that RS and FS exposure led to opposite changes in 5-HT1A antagonist binding through posttranscriptional mechanisms; RS led to decreases (CA3 and dentate gyrus), while FS led to increases (CA2 and cortex), though neither exposure affected 5-HT1A mRNA expression 124 . Based on these findings, the degree to which trauma exposure impacts 5-HT1A expression through transcriptional versus posttranscriptional mechanisms may vary by trauma type. Furthermore, when trauma exposure does impact 5-HT1A expression through posttranscriptional mechanisms, the direction of change and region affected may also depend upon trauma type. Taken as a whole, this evidence suggests that the impact of trauma exposure on 5-HT1A expression, including the region, direction, and mechanism of change, is influenced by and potentially dependent in part on the type of trauma an individual is exposure to.

Further supporting our proposal that different trauma types may alter 5-HT1A through different mechanisms, research suggests that alterations in the 5-HT1A repressor Freud-1 may play a role in altering 5-HT1A expression after some, but not all traumas. In one study, exposure to RS led to reduced Freud-1 mRNA and protein in the prefrontal cortex as well as the expected concurrent increase in prefrontal 5-HT1A mRNA in Sprague-Dawley rats 123 . In another study, exposure to CSD (approximates chronic exposure to interpersonal violence) led to decreased prefrontal 5-HT1A mRNA expression in Wistar rats without affecting Freud-1 mRNA expression 125 . Of note, researchers also used different strains of rats (Sprague-Dawley rats and Wistar rats), which may have contributed to observed findings. However, one study which used only one breed of rat examined the effect of nontraumatic stressors in the prefrontal cortex and found that each of four qualitatively different types of stress led to distinct alterations in both mRNA and protein levels of 5-HT1A, Freud-1, and NUDR (NUDR acts as a 5-HT1A autoreceptor repressor and 5-HT1A heteroreceptor enhancer) 126 . Overall, this evidence suggests that different types of stress, including different types of traumatic stress, can alter 5-HT1A expression through different mechanisms.

Preclinical pharmacological studies provide additional supporting evidence for our thesis that different types of traumas differentially affect 5-HT1A. Different types of trauma may differentially alter the physiological impact of 5-HT1A activity. One study found that pretreatment with the 5-HT1A agonist ipsapirone differentially affected increases in extracellular levels of adrenocorticotropic releasing hormone, corticosterone, and plasma renin concentration induced by RS, FS, and FC (approximates exposure to predictable physical harm) 127 . In addition, one study found that the 5-HT1A agonist 8-OH-DPAT attenuated the corticosterone response to FC but not RS or IES (approximates exposure to inescapable physical harm) 128 . Based on these results, the observed differential impact of trauma type on 5-HT1A alterations likely has downstream physiological consequences including altered neuro-endocrine functioning.

Though they examine different rodent strains and therefore do not include a direct comparison to other trauma types, additional studies suggest that specific trauma-induced 5-HT1A alterations may have specific behavioral consequences. For example, one study found that, in male Sprague-Dawley rats, SPS led to an increase in 5-HT1A expression in the hippocampal CA1 region as well as impaired spatial memory performance 129 . Local CA1 injection of the 5-HT1A agonist 8-OH-DPAT further exacerbated the SPS-induced impairment, suggesting an impairing effect of SPS-induced 5-HT1A upregulation in the CA1 on spatial memory 129 . By contrast, decreased 5-HT1A expression and activity in the prelimbic (PrL) cortex may be a critical mechanism of CSD-induced anxiety. One study found that, in female mandarin voles, CSD led to decreased 5-HT1A expression in the PrL, decreased PrL serotonin levels, and increased anxious behavior 130 . Local PrL injection of 8-OH-DPAT reversed the CSD-induced anxiety in exposed voles, while local PrL injection of WAY-100635 (a 5-HT1A antagonist) caused anxious behaviors in control voles 130 . Of note, in CSD-exposed voles, 5-HT1A autoreceptor expression was increased in the dorsal raphe nucleus (which projects to the PrL), suggesting that the decreased PrL serotonin levels were caused by a region-specific increase in 5-HT1A expression 130 . Overall, these results suggest that region-specific trauma-induced increases and decreases in 5-HT1A expression and activity may have impairing behavioral effects. Given that different types of trauma lead to different region-specific alterations in 5-HT1A, this suggests that the differences in behavioral impact observed in different trauma types may be related to the observed differences in 5-HT1A alterations.

Chronicity and duration of traumatic stress exposure and 5-HT1A alterations

As is the case with different types of traumas, preclinical results suggest that, when controlling for all other factors, differences in duration (time per exposure) or chronicity (days of exposure) lead to different alterations in 5-HT1A expression and 5-HT1A mRNA expression. For example, in one study, exposure to 30 min of FS led to an increase in 5-HT1A agonist binding and 5-HT1A antagonist binding in the hippocampus and cortex 124 . By contrast, exposure to only 15 min of FS did not alter 5-HT1A agonist binding or 5-HT1A antagonist binding in the hippocampus or cortex 124 . Similarly, findings from two studies suggest that exposure to 14 days of CUS led to a decrease in hippocampal 5-HT1A mRNA expression, but exposure to 7 days of the same CUS paradigm did not alter hippocampal 5-HT1A mRNA expression 42 , 119 . As the extent of trauma exposure leads to different clinical consequence in humans, preclinical evidence suggests that both duration and chronicity of exposure appear to impact 5-HT1A expression.

Differences in chronicity of trauma exposure can differentially impact 5-HT1A expression in complex ways. For example, in one study, exposure to CSD led to a transient increase in 5-HT1A binding in the claustrum, which was found when exposure lasted 2 days, but not when exposure lasted 10 or more days 43 . However, exposure to the same CSD paradigm led to a stable decrease in 5-HT1A binding in the posterior cingulate, which was found when exposure lasted 10, 21, or 28 days 43 . Exposure for 28 days also led to decreases in the parietal cortex, prefrontal cortex, regio retrobulbaris, and CA1 hippocampal region, which were not found when exposure lasted <28 days 43 . These results support a possible region-specific dose-response relationship between chronicity of trauma exposure and 5-HT1A binding. Interestingly, no change was detected in the raphe for any chronicity of CSD up to 28 days 43 . In another study, 2 h of exposure to RS led to an increase in hippocampal 5-HT1A binding when exposure lasted 1 day and a further increase in 5-HT1A binding when exposure lasted 5 days 131 . In contrast with the overall increase in hippocampal 5-HT1A binding observed between 1 and 5 days of exposure, increases in the CA4 subregion were transient; increases in 5-HT1A binding in the CA4 were observed when exposure lasted for 1 day but not when it lasted for 5 days 131 . Overall, findings suggest that changes in length of exposure may lead to distinct region-specific changes in the degree and direction of the relationship between trauma exposure and 5-HT1A expression; these changes can be transient in nature or delayed in onset. Taken together, preclinical findings support the assertion that differences in qualitative and quantitative aspects of trauma exposure contribute to variation in subsequent alterations in 5-HT1A expression.

Clinical/pharmacological implications

The exact role of 5-HT1A in the etiology of trauma-related psychiatric disorders is unclear. However, the prevailing consensus is that 5-HT1A is influential in the development of depression, anxiety, fear, and memory impairment 35 , 36 , 37 . In addition, one study finds that individuals with PTSD may have elevated 5-HT1A availability 76 . Further elucidation of 5-HT1A’s behavioral impact, including the degree to which it varies as a function of trauma history, may lead to the development of highly targeted treatments, and betterment of outcomes through personalized treatment 44 , 132 . For example, preclinical studies suggest that biased 5-HT1A agonists, which specifically target autoreceptor or heteroreceptor signaling, may be more effective in treating depression and anxiety than currently available 5-HT1A agonists 133 , 134 , 135 . In addition, recent literature suggests that drugs capable of acting on specific mechanisms of 5-HT1A expression could lead to major breakthroughs in treating depression 44 . However, targeting the correct mechanism for alteration of 5-HT1A may be critical 44 , 136 . Given the impact of trauma type and extent of exposure on 5-HT1A, we theorize that trauma history may be a crucial determinant of response to future breakthrough treatments.

In support of our theory, previous correlational studies and randomized controlled trials have found evidence to suggest that individuals with the same diagnosis but different trauma histories respond differently to currently available pharmacological treatments 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 . Thus, individuals with different trauma histories may require different pharmacological treatments, likely in part due to the differential effects of those trauma histories on gene expression. Failure to account for trauma history during pharmacological studies may obscure trauma-induced heterogeneity in responsivity, thus concealing a drug’s potential efficacy (or lack thereof) in individuals with particular trauma histories and delaying progress in clinical practice. Based on this evidence, in order to achieve personalized treatment, one must first account for the differential impact of different types of trauma and degrees of exposure.

5-HT1A as an exemplar

Though the primary focus of this review has been 5-HT1A, the implications of these findings likely extend to additional molecular targets. Multiple preclinical studies suggest that different types of trauma and degrees of exposure can lead to alterations in molecular targets other than 5-HT1A. For example, exposure to CUS led to multiple region-specific increases and decreases in dopamine D1-like receptor binding, but exposure to RS did not impact D1-like receptor binding in any of those regions 145 . Similarly, in the hippocampal CA2, exposure to RS led to an increase in serotonin-7 receptor mRNA expression but exposure to CUS did not 146 . Additional examples exist, including research focused on mu opioid and glucocorticoid receptors 147 , 148 . Similarly, multiple studies have found evidence to suggest that different types of trauma exposure and different degrees of trauma exposure differentially affect gene expression in humans 149 , 150 , 151 , 152 , 153 . For example, in one study, profiles of gene expression in peripheral blood cells which distinguished individuals with PTSD from controls were almost completely distinct (98% nonoverlapping), depending on whether subjects with PTSD had a history of childhood abuse exposure 153 . Importantly, in addition to PTSD, the impact of trauma type and degree of exposure on gene expression has been evident in individuals with MDD and borderline personality disorder 150 . Taken together, these studies provide direct evidence for the importance of trauma type and degree of exposure in modulating the effect of trauma on genetic expression, which extends beyond 5-HT1A and beyond PTSD.

Previously, we synthesized evidence to suggest that different types of traumas can alter 5-HT1A through different mechanisms, including the 5-HT1A repressor Freud-1. A closer examination of specific mechanisms of 5-HT1A alterations provides a useful paradigm for understanding the complexity of the concurrent impact of different trauma types and degrees of exposure on many molecular mechanisms. For example, the 5-HT1A repressor Freud-1 also represses the dopamine receptor D 2 154 . Thus, differences in the impact of various types of trauma on Freud-1 likely lead to differences in expression of not only 5-HT1A, but also D 2 and any other mechanisms affected by Freud-1. In addition, we provided evidence that different types of stressors differentially impact the dual-effect 5-HT1A autoreceptor repressor and 5-HT1A heteroreceptor enhancer NUDR. In addition to its effect on 5-HT1A, NUDR also regulates transcription of Proenkephalin 155 . Notably, many transcriptional and posttranscriptional mechanisms of 5-HT1A expression also affect multiple molecular targets 44 . For example, the 5-HT1A autoreceptor enhancer Pet-1 also plays a role in activating expression of the nicotinic acetylcholine receptor 156 , 157 . In addition, 5-HT1A promotors MAZ and Sp1 decrease NMDA receptor subunit type 1 promoter activity 158 , 159 . Furthermore, in addition to posttranscriptional regulation of 5-HT1A, miR-135a also regulates the serotonin transporter, PHLPP2, and FOXO1 44 . These findings illustrate the general principal that the mechanisms underlying differential impacts of trauma type and chronicity of exposure on 5-HT1A expression likely lead to differential impacts on other molecular targets as well. Furthermore, they provide insight into the fact that traumatic stressors may regulate a wide array of molecular targets through diffusely acting mechanisms.

Limitations and future directions

This paper does not provide an exhaustive review of the literature on 5-HT1A and trauma. Many studies which found alterations in 5-HT1A expression induced by rodent trauma models were excluded from mention in this work due to a lack of direct comparability arising from methodological discrepancies 58 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 . Future preclinical studies can further elucidate the impact of differences in trauma type and extent of exposure on changes in the expression of 5-HT1A and other molecular targets by consciously and deliberately accounting for trauma type. One particularly noteworthy gap in the current literature concerns early life trauma. To date, models of early life trauma have been associated with increases 183 , decreases 174 , or no change 184 in 5-HT1A expression. However, methodological differences (e.g., rodent strain, rodent sex, chronicity of exposure, additional experimental stressors, time since trauma exposure at sacrifice, and index of 5-HT1A expression) preclude direct comparisons between trauma models or between different developmental periods as they relate to 5-HT1A expression. Future studies should endeavor to resolve this issue.

More studies are needed in order to identify relationships between specific categories of trauma and resultant alterations in gene expression. In addition, these findings have yet to be extended to humans. Only one published study in humans has evaluated the relationship between 5-HT1A and trauma exposure, with null results 185 . Of note, however, trauma type was not controlled for and authors acknowledged that the study may have lacked sufficient power to detect an association 185 . Future studies should examine the association between trauma and 5-HT1A expression in humans, specifically with respect to differences in trauma type and chronicity of exposure. Given the known adverse impacts of aversive childhood experiences and the divergence in genetic expression associated with childhood and adult trauma, differences in developmental timing of trauma should also be considered.

While it seems clear based on the reviewed preclinical literature that trauma type and chronicity of exposure impact gene expression, no available preclinical studies examining 5-HT1A distinguish behaviorally affected and resilient individuals. In the preclinical literature, the importance of separating behaviorally affected animals from resilient animals is becoming increasingly clear 82 , 83 . Studies have found that some post-trauma alterations in gene expression that are present in the group average may only apply to affected animals, while others may only apply to resilient animals 82 , 83 . Thus, with the exception of studies that measure the behavioral effects of 5-HT1A agonists or antagonists in addition to measuring gene expression, most currently available studies do not provide information to distinguish adaptive alterations in 5-HT1A from maladaptive alterations. Future studies should apply methodology such as cut-off behavioral criteria and behavioral profiling in order to distinguish alterations in 5-HT1A that are seen in resilient animals from those seen in affected animals. Of note, cut-off behavioral criteria and behavioral profiling are applied analytically to postexposure behavioral data and do not necessarily require a change in study design 82 , 83 . Thus, it may be possible to apply these techniques to archival data. Though some research questions may require the design of new studies in order to incorporate specific behavioral effects of interest, we recommend applying cut-off behavioral criteria and/or behavioral profiling to archival data wherever feasible. In addition to being highly practical, the use of archival data is in line with ethical best practice as it does not cause any additional suffering to animals 186 .

This review focuses on the importance of considering differences in the nature and chronicity of trauma exposure in neurobiological research. However, other key variables warrant similar consideration. Specifically, recent research has emphasized the importance of sex differences, risk factors, and individual differences in response to the same trauma 82 . We propose that these two approaches need not be mutually exclusive. For example, in rodents, qualitatively different types of nontraumatic stressors have been found to lead to sex-dependent differential alterations in mRNA and density of 5-HT1A and specific 5-HT1A transcription factors 126 . Future studies should examine the degree to which the interaction of stressor type and sex extends to rodent trauma models and human trauma exposure. This approach could also be extended to other relevant risk factors, such as inherited genetic differences, which are shown to alter trauma’s impact on 5-HT1A expression as well as behavior 182 . Specific single nucleotide polymorphisms alter the ability of specific mechanisms to impact gene expression 187 . Specific mechanisms underlying the relationship between trauma and gene expression depend on trauma type and level of exposure. Therefore, future studies should investigate specific interactions between genes, sex, and trauma type as they relate to 5-HT1A expression.

Conclusions

We have presented preclinical evidence supporting our contention that differences in the type and chronicity of exposure to trauma leads to differences in the region-specific posttraumatic alterations in 5-HT1A. Furthermore, differences in the nature of trauma and extent of exposure to trauma appear to lead to differences in the mechanisms underlying changes in 5-HT1A expression; even when two different traumas lead to the same directional change in 5-HT1A expression in a given region, it is possible that different mechanisms are driving the change. Furthermore, this phenomenon does not appear to be specific to 5-HT1A and evidence suggests that it may translate to humans. Based on the evidence presented in this review, future studies aimed at understanding the differential molecular alterations that are generally associated with certain categories of trauma exposure may eventually inform a more targeted approach to pharmacological treatments for trauma-exposed individuals. In order to understand the neurobiology of trauma, it is crucial to consider both trauma type and extent of exposure.

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Lewis, M.W., Jones, R.T. & Davis, M.T. Exploring the impact of trauma type and extent of exposure on posttraumatic alterations in 5-HT1A expression. Transl Psychiatry 10 , 237 (2020). https://doi.org/10.1038/s41398-020-00915-1

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Sophie Isobel, Andrea McCloughen, … Kim Foster

research paper about trauma

Trauma and Trauma-Informed Care

research paper about trauma

Systematic Review on the Application of Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) for Preschool-Aged Children

Austen McGuire, Ric G. Steele & Mehar N. Singh

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Introduction

As recognized by William Faulkner and Judith Herman, as well as by many other writers and mental health professionals, trauma can take a tremendous psychological toll that may not disappear even with the passage of time. The term “trauma” comes from the Greek language meaning a “wound” or “hurt” (Oxford Dictionaries, 2013 ). Psychologically, “trauma” refers to an experience that is emotionally painful, distressful, or shocking, and one that often has long-term negative mental and physical (including neurological) consequence. An event is thought to produce a traumatic response when the stress resulting from that event overwhelms the individual’s psychological ability to cope (McGinley and Varchevker 2013 ).

Although we often think of trauma as being synonymous with the identified objective cause of the trauma, such as a soldier losing his legs to a roadside bomb explosion, the effect of the trauma is always subjective and refers to the impact—the perceived “wound” or “hurt” as identified by the early Greeks—that it has on the individual (Miller 2004 ). Thus what might be a traumatizing, life-shattering event for one individual might have minimal effects on another. Such differential reaction is based on many factors, including the individual’s age, gender identity, pre-morbid ego strength, previous traumatic experiences, the chronicity of the trauma, family history of trauma, current life stressors, social supports, and one’s cultural, religious or spiritual attitude toward adversity (Amir and Lev-Wiesel, 2003 ; Brewin et al. 2000 ; Felitti et al. 1998 ; Foa et al. 2009 ; Stamm and Friedman 2000 ; Straussner and Phillips 2004a ).

Unfortunately, the experience of trauma is not uncommon. Although there is a lack of recent national epidemiological findings about trauma among adults [Centers for Disease Control and Prevention (CDC) 2006 ], studies during the 1990s found that over 60 % of men and 51 % of women in the United States report having experienced at least one traumatic event during their lifetime (Giaconia et al. 1995 ; Kessler et al. 1995 ). Traumatic stress can cause disorganization of thinking, awareness, impaired judgment, altered reaction time, hyper vigilance, and unhelpful attempts at coping. While most people will experience time limited reactions, such as acute stress disorder, a smaller percentage may continue to manifest more severe and often longer lasting trauma-related impacts. These may include panic disorders, depression, sleep disorders, substance use disorders, as well as post-traumatic stress disorder (PTSD) (Kessler et al. 1995 ; Leskin and Sheikh 2002 ; Ringel and Brandell 2012 ).

While trauma can impact an individual at any time in the life cycle, from pre-natal development through old age, the impact and the treatment approaches vary depending on the individual’s developmental needs and the psychosocial environment. The purpose of this article is to provide an overview of common traumatic events and responses with a specific focus on the life cycle—identifying selected traumas encountered during childhood and adolescences, adulthood and late life. The differential impact of trauma on men and women, on immigrants, transgenerational transmission of trauma, the concept of resilience, and the implications for the treatment of traumatized individuals at the different stages of the life cycle are identified.

Nature of Trauma: “Large T” and “Micro-Traumas”

There are many different kinds of traumas, ranging from what Francine Shapiro, the originator of Eye Movement Desensitization and Reprocessing (EMDR) treatment approach (Shapiro 1995 ) has termed “large - T” traumas to “ small - t” or, what Straussner ( 2012 ) refers to as “micro-traumas.” Large-T traumas can impact individuals, families, groups and communities and include natural disasters, such as hurricanes, floods, wildfires, or nuclear disasters, as well as human-caused disasters, such as deadly car accidents, individual and mass violence, and other one-time traumatic events. Large-T traumas can also include, what Judith Herman ( 1997 ) termed as “complex traumas,” and which others refer to as Complex Traumas and Disorders of Extreme Stress (DESNOS- disorders of extreme stress not otherwise specified )—traumas that involve events of prolonged duration or multiple traumatic events (van der Kolk, Roth, Pelcovitz, Sunday and Spinazzola, 2005 ). Examples of complex, large-T traumas [also referred to as Type II trauma by Terr (1991)], include on-going interpersonal violence, child physical or sexual abuse spanning several years, never-ending wars, or constant acts of terrorism.

Small-t or micro-traumas are the more common traumas encountered by many of us. While large-T traumas are easily identified, many micro-traumas, such as being bullied in school or in the workplace (Idsoe et al. 2012 ; Mishna 2012 ), being stalked by someone (Purcell et al. 2005 ), living in severe poverty (Kiser 2007 ), childbirth (Kendall-Tackett 2013 ), or being the recipient of on-going individual discrimination because of one’s race, religion, gender identity, or sexual orientation, often go unrecognized and unacknowledged. Yet these micro-traumas may still cause much psychic pain and life-long damage.

Exposure to and Impact of Trauma

In her classic book Shattered assumptions: Towards a new psychology of trauma , Janof-Bulman ( 1992 ) reflects on the psychological shattering of one’s worldview experienced by traumatized individuals, especially if the trauma is caused through deliberate human acts (Straussner and Phillips 2004a ). Whereas the world was previously viewed as being trustworthy and benevolent, this belief may become transformed into the sense that “people will hurt me, and I can’t trust anyone.” Additionally, trauma survivors might find that the world they used to perceive as being stable and predictable, now seems unpredictable and out of their control. Consequently, their previous sense of empowerment and of being in control of their environment and their lives gives way to one in which they feel disempowered, helpless, and unable to predict and plan for the future. They may even have a sense of being psychologically damaged and defective (Janof-Bulman 1992 ).

The idea that trauma could result in specific clusters of symptoms first became formalized by the inclusion of the diagnosis of PTSD in the third edition of the Diagnostic and Statistical Manual of Mental Disorders [DSM; American Psychiatric Association (APA) 1980 ]. This new diagnostic category was precipitated by awareness of the psychological problems experienced by returning Vietnam War veterans in the late 1970s and the growing literature by European writers who survived their own traumatic experiences during the Second World War—such as Gunter Grass, Primo Levy, and Eli Wiesel among others—and who vividly described the profound impact of mass violence on individuals, families and communities (Straussner and Phillips 2004a ). Studies of survivors of the Nazi-caused Holocaust (Krystal and Niederland 1968 ) and of the Hiroshima atomic bombing by the United States (Lifton 1968 ), introduced the concept of “survivors’ guilt” into our vocabulary.

The more recent recognition that traumatic reactions can result from response to events other than war, such as sexual assault, exposure to child abuse, domestic violence, and accidents has made PTSD a widely recognized disorder throughout the world (Herman 1997 ; van der Kolk et al. 2005 ). The importance of PTSD as a diagnostic category is reflected in the newly revised DSM-5 (APA, 2013 ), where PTSD and related conditions are no longer listed under Anxiety Disorders or Adjustment Disorders as previously, but are located in a separate chapter titled “Trauma- and Stressors-Related Disorders.”

While the experience of trauma is common, PTSD diagnosis is relatively rare. The estimated lifetime prevalence rate of PTSD in the US is thought to range between 6 and 12 %, averaging around 9 % of the population (APA 2013 ; Breslau et al. 1991 ; Kessler et al. 1995 ; Resnick et al. 1993 ). However, the initial prevalence rates among active duty military exposed to war conditions and among survivors of mass trauma, such as the September 11, 2001 World Trade Centers in New York, can range as high as 30 % and more (Galea et al. 2005 ; Susser et al. 2002 ). According to the latest edition of the DSM, the “[h]ighest rates (ranging from one-third to more than one-half of those exposed) are found among survivors of rape, military combat and captivity, and ethnically or politically motivated internment and genocide” (APA 2013 , p. 276). Recent United States- based studies document higher rates of PTSD among African-Americans, Latinos and American Indians than among white or Asian populations (APA 2013 ). International annual prevalence rates are believed to be somewhat lower than those in the US (APA 2013 ; Landolt et al. 2013 ), although studies in areas with on-going conflict, such as in Israel and the Palestinian territories, point to rates that are similar to those in the US among individuals who have been or are still exposed to combat (Dimitry 2011 ; Gelkopf et al. 2008 ; Solomon et al. 1996 ).

As pointed out earlier, trauma has a differential impact depending on age, gender, and psychosocial factors, which are discussed below.

Trauma and Children

As is recognized in the new Diagnostic and Statistical Manual (DSM-5; APA 2013 ), while trauma has a profound impact on all individuals, its impact on young children is unique and particularly pernicious. Millions of children throughout the world are currently growing up amidst traumatic environments—they are being sexually and physically abused at home, bullied at school, and traumatized in their communities (Finkelhor et al. 2009 ). Many lack adequate food and shelter, and some live in unsafe communities and war zones witnessing violence occurring to friends and family, including rape, torture and murder. Numerous studies have shown evidence of long term repercussions of exposure to violence at an early age (Anda et al. 2006 ; Steele 2004 ). The implications of exposure to trauma are now believed to have an effect on the infant even before birth. A more detailed discussion of the impact of trauma on children follows, starting with prenatal impact.

Prenatal Impact

Preliminary research shows that children are impacted even before birth by trauma that is experienced by their mothers. Studies in New York City comparing pregnant women who were close to Twin Towers on September 11 and suffered “post traumatic stress syndrome” (PTSS) with pregnant women who were in different locations, found that newborns of mothers manifesting PTSS had significant smaller head circumference at birth (Engel et al. 2005 ). As we know, decrements in head circumference influence subsequent neurocognitive development. More recent studies, using modern technologies such as Functional MRI, reveal that fetal exposure to maternal stress is significantly associated with a variety of impacts on brain activity, endocrine function, and on autonomic nervous system function (Sandman and Davis 2012 ). While these studies have small sample sizes and need to be validated further, we are recognizing that it is not enough to assess, when appropriate, whether a child was born prematurely or not, or whether the mother was malnourished during pregnancy, but also whether she was being abused by her husband or partner, or lived in a violent community or a war zone during her pregnancy, and how this may be related to the some of the problems exhibited by her children (Lieberman and Van Horn 2008 ; Pine and Cohen 2002 ). It is also worth noting that the biophysiological impact of paternal trauma on the fetus and newborn child has yet to be considered as worth studying, even though there is growing evidence that spontaneous changes in genetic makeup in the sperms of fathers impacts on the mental health of their children (Kandel 2013 ). Whether paternal trauma impacts the sperm, and thus the child, needs to be researched in the future.

Impact on Young Children and Adolescents

The impact of trauma on the brain of traumatized children continues after birth and even during adolescence and young adulthood, as evidenced by recent studies suggesting that the brain continues its development until age 25 (Cicchetti and Curtis 2006 ; Giedd 2008 ). Trauma, particularly complex or ongoing trauma in early life, affects brain development, especially the development of right hemispheric brain functions, which include among other things, regulation of mood and social adjustment. Moreover, “[n]europsychological studies suggest an association between child abuse and deficits in IQ, memory, working memory, attention, response inhibition, and emotion discrimination. Structural neuroimaging studies provide evidence for deficits in brain volume, gray and white matter of several regions, most prominently the … prefrontal cortex but also hippocampus, amygdala, and corpus callosum (CC). Diffusion tensor imaging (DTI) studies show evidence for deficits in structural interregional connectivity between these areas, suggesting neural network abnormalities” (Hart and Rubia 2012 p. 52). While the authors acknowledge the limitations of such studies, particularly the lack of control for co-morbid psychiatric disorders, which make it difficult to disentangle which of the above effects are due to maltreatment, other researchers have found that even indirect exposure to trauma, such as witnessing family or community gang violence, plays an important role in altering brain mechanisms involved in the processing of emotions and may predispose children to problems managing strong emotions and difficulty with emotional regulation. Such children appear to experience changes in stress hormonal regulatory systems and neural patterns that are associated with heightened emotional reactivity as well as weakened emotional resiliency, increasing their vulnerability to problematic behaviors, future traumas, as well as their own potential for violence (Grasso et al. 2013 ; Heide and Soloman 2006 ).

Data from the well regarded Adverse Childhood Experiences (ACE) study (Felitti et al. 1998 ) suggests that ACEs are “related to a greater likelihood of developing a variety of behavioral, health, and mental health problems, including smoking, multiple sexual partners, heart disease, cancer, lung disease, liver disease, sexually transmitted diseases, substance abuse, depression, and suicide attempts” (Lu et al. 2008 p. 1018).

Various authors have identified other negative consequences resulting from exposure to trauma during early life:

Preschool children are likely to exhibit passive reactions and regressive symptoms, such as enuresis, decreased verbalizations and clinging behavior, indicative of anxious attachment (APA 2013 ; Lieberman and Van Horn 2008 ; Steele 2004 ).

School age children may display both more aggression and more inhibition. They also develop somatic complaints, depression, sleep disturbance, cognitive distortions and learning difficulties manifested by impaired concentration and memory problems (Steele 2004 ; Terr 1991 ).

Adolescents exposed to trauma tend to respond by acting-out and self–destructive behavior: substance abuse, promiscuity, delinquent behavior, and life-threatening reenactments of violent episodes (APA 2013 ; Bava and Tapert 2010 ; Brent and Silverstein 2013 ; Garbarino et al. 1992 ; Pat-Horenczyk et al. 2007 ).

Children and adolescents who witness the death of close friends or family members may experience survivor guilt (Herman 1997 ; Steele 2004 ).

Like many traumatized adults, children may exhibit classic symptoms of PTSD without any understanding of what is going on with them (Derluyn et al. 2004 ).

Some children exposed to severe trauma may not show many of the classical trauma symptoms until later in life, reflecting the new DSM-5 specifier of “delayed expression” (APA 2013 ).

Children may exhibit traumatic bonding reflecting maladaptive attachment as well as inappropriate modeling of the behaviors of their abusers (a behavior also seen in adults and known as “identification with the aggressor” or “the Stockholm syndrome”) (Cohen et al. 2006 ; Derluyn et al. 2004 ; Weierstall et al. 2012 ).

Studies show that almost 100 % of those witnessing the murder or the sexual assault of a parent, and 35 % of urban youth exposed to community violence develop PTSD, although some of these highly traumatized children are more resilient than others (Derluyn et al. 2004 ; Garbarino et al. 1992 ; Malmquist 1986 ).

These young people with a history of, or current trauma need to be identified and treated in order to prevent life-long physiological, cognitive, emotional, behavioral, and social sequelae of their traumas (Anda et al. 2006 ).

Impact of Trauma on Adults

Ever since the tragedy of September 11, 2001 much has been researched and written about the impact of trauma on adults, especially in the United States. A exploration of the literature finds a variety of specialized journals devoted to this topic (to wit: Journal of Trauma Practice , Journal of Loss and Trauma , Journal of Traumatic Stress , Traumatology , International Journal of Emergency Mental Health , Journal on Rehabilitation of Torture Victims and Prevention of Torture, among others), as well as various textbooks aimed at different health professions, including social work (e.g., Courtois and Ford 2009 ; Foa et al. 2009 ; Ringel and Brandell 2012 ; Straussner and Phillips 2004b , etc.). What we would like to emphasize in this article are some of the lesser known factors effecting millions of adults by focusing on gender differences Footnote 1 and the impact of trauma on immigrants and refugees.

Gender and Trauma: What Do We Know?

Studies have found that men and women experience trauma in very different ways with somewhat different consequences. For instance, while men are much more likely to experience trauma, women are more likely to develop PTSD (APA 2013 ): for every traumatized man, three women have a lifetime prevalence rate of PTSD (Foa et al. 2009 ). Moreover, men are two times as likely as women to experience trauma due to physical assault, yet women are fifteen times more likely to develop PTSD as a result [World Health Organization (WHO), 2011 a]. While there are a variety of hypothesized explanations for these findings, ranging from the fact that women are more likely to seek professional help than men to possible neurobiological and hormonal differences, to women’s greater exposure to intrusive interpersonal violence (Hien et al. 2009 ), there is a lack of conclusive studies explaining these findings. Moreover, it appears that for men the most common factors associated with a diagnosis of PTSD are: rape, combat exposure, childhood neglect, and childhood physical abuse, while women are most likely be diagnosed with PTSD that is associated with sexual molestation, physical attack, being threatened with a weapon, and childhood physical abuse (Janof-Bulman 1992 ). These differences are particularly noteworthy among young adults. Recent data on military veterans show that over 15 % of US women veterans returning from the wars in Afghanistan and Iraq report being sexually traumatized in the military compared to .7 % of the men (Kimerling et al. 2010 ; Risen 2012 ).

Violence against women seems to be a growing worldwide pandemic. According to Key Facts Regarding Intimate Partner and Sexual Violence Against Women in the World , published by the World Health Organization (WHO 2011 a):

Violence against women is a major public health problem and violation of women’s human rights. Approximately 20 % of women report being victims of sexual violence as children.

The WHO multi-country study found that between 15 and 70 % of women reported experiencing physical and/or sexual violence by an intimate partner at some point in their lives, ranging from the extremely high rate of 70 % of women in Ethiopia and Peru to a low rate of 15 % among women in Japan.

First sexual experience for many women is reported as forced, with 40 % of young women in South Africa having such an experience. Such violence results in physical, mental, sexual, and reproductive health problems, and may increase the vulnerability of women to HIV/AIDS.

Population-based studies of relationship violence among young people (i.e., “dating violence” or “date rape”) show that it affects a substantial proportion of youth throughout the world. Moreover, worldwide, 1 in 2 female murder victims are killed by their male partners, often during an ongoing, abusive relationship.

Finally, situations of political conflict, post conflict and displacement may exacerbate existing violence and present new forms of violence against women.

Trauma and Immigration/Migration

In 2010, some 214 million people—3 % of the world’s population—lived outside of their country of origin (Batalova and Lee 2012 ). While many people migrate for positive reasons, the so called pull factors –to seek better education or jobs, to reunite with family, and so on—more and more people today move for negative reasons, or push factors , i.e. they are being pushed from their home communities due to natural disasters, economic situations, or local conflicts and wars (Castex 2006 ). Worldwide, there are currently over 15 million refugees uprooted from their home countries, the highest number since the 1990s Rwandan genocide (McClelland 2014 ). For many of these individuals, trauma is compounded by grief over loss—loss of family members and friends, loss of homes, neighborhoods, language, and even familiar smells. Cultural anchors, such as local religious and educational institutions, familiar medicines, native healers and/or known medical and psychological treatment approaches are missing. For many, particular political refugees and those with undocumented status, migration itself becomes traumatic with numerous obstacles along the way and an uncertain future. For some, prejudice and discrimination, lack of recognition of previously achieved economic and personal status (the micro-traumas) compound the reactions. For those whose migration status is undocumented or illegal, seeking or obtaining help for their big T, much less their micro-traumas is often impossible; thus their trauma may remain unresolved and may carry over to the next generation.

The dynamics of intergenerational transmission of trauma was first identified in studies of adult children of Holocaust survivors (Danieli 1998 ; Yehuda et al. 2001 ). The growing attention in the US on what is being termed “historical trauma”, relating mainly to Native American populations (Heart 1999 ), and “Post Traumatic Slave Syndrome” (DeGruy Leary 2006 ), which focuses on the consequences of slavery on African Americans, point to the increasing recognition and need to address the psychological, social, political, and cultural impact of widespread trauma over time . A study by Mollica et al. ( 1998 ) found that in a group of Cambodian survivors the impact of trauma remains decades after the original experience and that mental health symptoms may increase when individuals experience additional traumas, findings that were confirmed by other researchers studying refugee populations from different parts of the world (Bogic et al. 2012 ; Steel et al. 2002 ). Thus, the frequency of traumatic events (multiple traumatic exposures) is an important predictor of long term mental health outcomes, especially for traumatized refugee populations.

Trauma and Older Adults

The finding that cumulative trauma is more likely to increase the risk of poor psychiatric outcomes is of particular relevance to aging populations. The global population of people aged 60 years and older is expected to reach about 1.2 billion in 2025, more than doubling in the last 30 years (WHO 2011 b). As the world’s population ages, the special issues of trauma among the elderly need to be recognized more widely. The concept of “cumulative life stressors” is well known in the psychosocial literature (Dohrenwend 1998 ), and “cumulative trauma” is seen as reflecting multiple traumas experienced by an individual in multiple situations (Landau and Litwin 2000 ; Mollica et al. 1998 ). Thus the older an individual, the more likely he or she is to have been exposed to a variety of traumatic situations, and the more frequent exposure to life-threatening events has been associated with a lower capability to handling stress and higher risks of PTSD (Brandler 2004 ; Ursano et al. 1995 ). Moreover, the elderly are at a greater risk for psychological distress post- disaster than middle aged adults due to a greater risk for bodily injury, loss of resources, and lack of social networks or supports (Marsella 2008 ; Ursano et al. 1995 ). These issues play an even greater role among disabled older adults who are dependent on others for both physical as well as emotional support.

While the elderly may suffer trauma from the same sources as younger people, like children they are particularly vulnerable to being maltreated or abuse at home and even more so in institutions aimed to protect them, such as nursing homes and hospitals. According to the WHO ( 2011 b), an estimated 4–6 % of elderly people in high-income countries have experienced some form of maltreatment at home. Many of the abusive acts against the elderly in homes or institutions consist of micro-traumas, such as: being physically restrained, deprived of dignity by being left in soiled clothes, being over- or under-medicated, and emotionally neglected and abused. One study found that more than half the residents of intermediate care facilities were receiving psychoactive drugs and 30 % received long-acting drugs not recommended for elderly persons (Beers et al. 1988 ). Some acts against older adults do rise up to the level of large-T traumas of physical abuse that can be life threatening or can result in serious, long-lasting, psychological consequences, including depression, anxiety and PTSD.

While accurate, generalizable data are scarce (Ben Natan and Lowenstein 2010 ), one survey of nursing-home staff in the US, found that (Pillemer and Moore 1989 ):

36 % witnessed at least one incident of physical abuse of an elderly patient in the previous year;

10 % committed at least one act of physical abuse towards an elderly patient;

40 % admitted to psychologically abusing patients.

For those cared for at home, studies indicate that the social isolation of both caregivers and the older adults, and the ensuing lack of social support, is a significant risk factor for elder maltreatment by caregivers. Thus help needs to be provided not only to the elderly, but also to their caregivers.

Moreover, when dealing with community trauma, whether natural, such as earthquakes, or man-made, such as a terrorist attack, or individual micro-traumas, such as having a spouse who has been diagnosed with Alzheimer’s, older adults are particularly vulnerable to what has been termed as “ambiguous loss” (Boss 2009 ) or “disenfranchised grief” (Doka 1989 ). For example, while the parents of an adult son killed in a terrorist attack may be acknowledged and supported by the community, the great-aunt of the murdered young man may be totally ignored, even though for many years he may have been her major source of emotional support. Finally, it is important to recognize that the nature of trauma among older adults varies among different ethnic and racial groups, even in the same community (Marsella 2008 ). For example, Higgins and Park ( 2012 ) in a comparison of African American and Caribbean Black older adults in New York found that African Americans experienced more spousal abuse, incarceration, and combat involvement, while Caribbean Black older adults experienced more natural disasters.

Trauma and Resilience: A Strength-Based Perspective

As George Bonanno ( 2004 ) reminds us, as professional helpers we tend to see people who have difficulties coping with trauma. We thus forget that many people are exposed to traumatic events at some point in their lives, and yet they continue to have positive emotional experiences and show only minor or transient disruptions in their ability to function. The concept of resilience reflects the individual’s ability to effectively use resources in the environment, notably relationships with others, as well as their own internal resources and potentialities (Bonanno et al. 2007 ; Bonanno et al. 2011 ). Hauser ( 1999 ; Hauser et al. 2006 ) point out that resilience is a process, not a state. Doing longitudinal studies of youth, most of whom were physically and sexually abused at home and then put into psychiatric hospitals, the authors found that those young men, who as adults were able to achieve a satisfying life despite horrendous childhoods, reflected three general characteristics:

A belief that one can influence one’s environment (self efficacy),

The ability to handle one’s thoughts and feelings (cognitive-behavioral skills), and

The capacity to form caring relationships.

What is important to note is that these traumatized yet resilient youth did not show a normative development. Their lives had not been easy; they made seemingly unwise choices and often got into social and legal troubles. What characterized them was, however, an ability to learn from experience . The authors point out is that “Resilience does not lie in either the competence or relationship; it lies in the development of competence or relationship where they did not exist before” (Hauser et al. 2006 , p. 261). It is this ability to learn from one’s traumatic experience and to achieve what we now refer to as Post - Traumatic Growth (PTG) (Tedeschi and Calhoun 2004 ; Zoeller and Maercker 2006 ) that is the ultimate goal of effective trauma treatment.

Treatment Approaches with Traumatized Individuals

The last few decades have brought extensive research and innovative treatment approaches to helping traumatized individuals. Since, as indicated previously, the experiencing and the consequences of trauma are highly subjective, there is no single treatment approach for helping all individuals who have experienced and suffered trauma, and particularly those suffering from chronic PTSD. Moreover, as trauma can occur at different ages, interventions must be age appropriate as well as gender and culturally relevant.

Interventions with Traumatized Children

As with traumatized adults, the main goal of treatment with traumatized children is to engage them in activities and experiences that allow them to safely express feelings, regulate their emotions and manage overwhelming sensations. The natural language of young children is play. Play therapy, and related expressive arts therapies (Harris 2007 ), provide a way for the child to reenact the traumatic event through symbolic play and movement, and is an empirically-based intervention for working with traumatized children from the age of 3–11 (Bratton et al. 2005 ; Malchiodi 2008 ; Ryan and Needan 2001 ; Webb 2011 ). Play therapy with a caring, empathic adult allows the traumatized child to develop a sense of trust and provides an opportunity to achieve a sense of control over their trauma (Steele 2004 ; Webb 2011 ). While play therapy is usually conducted with an individual child, other approaches focus on involving the parents, and include:

Child-Parent Psychotherapy (CPP) (Lieberman and Van Horn 2008 ). CPP is a psychodynamically based therapeutic approach has shown to be very effective in treating trauma in young children while working with parents to repair the impact of the trauma to the family system. CPP is a flexible, culturally sensitive intervention that can be utilized in unstructured weekly session over the course of a year. It focuses on helping the child to rebuild trust by creating a trauma narrative where the caregiver can act out the protective role through the use of play. CPP has been supported by a number of randomized trials showing efficacy in increasing attachment security and maternal empathy (Berlin et al. 2008 ).

Parent–Child Interaction Therapy (PCIT; Eyberg and Bussing, 2010 ). While not specific to traumatized children, it is an empirically-based behavioral short term intervention for children age 2–7 who are experiencing emotional and behavioral disorders. PCIT draws on both attachment and behavioral theories and is provided over the course of 12 1-h weekly sessions. PCIT involves the parent interacting with the child with the therapist observing through a one-way mirror and coaching through a hearing aid device. The coaching consists of helping the parents to utilize two sets of skills: a. Child Directed Interaction, which teaches parents to use traditional play therapy techniques, and b. Parent Directed Interaction, which teaches the parents skills to address disruptive behaviors while increasing compliance by the child. These skills include establishing rules, praising compliance, using time-out chair for non-compliance, and so on (Ware et al. 2008 ).

Trauma-Focused Cognitive Behavioral Therapy (TF-CBT; Cohen and Mannarino 2008 ).

TF-CBT is a psychosocial intervention found to be effective in treating PTSD and other behavioral and emotional problems related to a variety of traumatic experiences in children and adolescents. It can be used with children and parents in individual and conjoined sessions, as well as in multi-family groups. TF-CBT usually lasts from 12 to 16 sessions. The treatment model focuses on applying the acronym PRACTICE, which summarizes the nine components of this model: Psychoeducation and parenting skills; Relaxation skills; Affect expression and regulation skills; Cognitive coping skills and processing; Trauma narrative; In-vivo exposure (when needed); Conjoint parent–child sessions; and Enhancing safety and future development (Cohen and Mannarino 2008 ; Cohen et al. 2006 ).

Intervention with Traumatized Adults

Many different treatment approaches have been shown to be effective for traumatized adults. They include: Psychoeducation, cognitive behavioral therapy, exposure therapy, desensitization and imaginal flooding, Eye Movement Desensitization and Reprocessing (EMDR), narrative therapy, group therapy and medications.

Psychoeducation

Psychoeducation is the “process of teaching clients with mental illness and their family members about the nature of the illness, including its etiology, progression, consequences, prognosis, treatment and alternatives” (Barker 2003 , p. 347). While there has been limited empirical evidence proving the importance of psychoeducation (Lukens and McFarlane 2004 ), clinical experience has shown that understanding the physiological responses to trauma can help individuals develop new coping strategies in dealing with others and learning to calm oneself physically (Creamer and Forbes 2004 ). It has also been shown to improve the quality of life for family members traumatized by others or to better understand the sometimes irrational behaviors of their traumatized loved one (Solomon et al. 2005 ).

Cognitive Behavioral Therapy [CBT]

CBT has been shown to be very effective at helping individuals who have experienced trauma by dealing with their thoughts and beliefs, as well as with their behavior patterns. Among the various empirically-based CB treatments are:

Exposure/Desensitization, which consists of direct confrontation with trauma by having individuals visualize the event, talk about it, and expose themselves gradually to stimuli which reminds them of the trauma. This is repeated several times until the person becomes accustomed or desensitized to these thoughts and images. Through these repeated exercises, the traumatic memory becomes just a regular memory, allowing the individual to have a sense of control rather than feeling helpless over the past traumatic event. One particular approach is known as “Prolonged Exposure” (PE; Foa et al. 2007 ), and is rooted in the tradition of exposure therapy for anxiety disorders and emotional processing for PTSD. PE uses both imaginal exposure (confront feared trauma memories and thoughts via imagining the feared object, event, or situation), and in vivo (experience/confront feared objects, places, events, and situations in real world settings). Individuals also are provided with psychoeducation on trauma reactions and on the use of PE to reduce symptoms, as well as breathing training to manage their anxiety. PE may not be appropriate for individual who have a history of multiple traumas (particularly in childhood), those with anger problems, and those who dissociate (Foa et al. 2007 , 2009 ).

Another empirically supported cognitive-behavioral treatment for PTSD is Dialectical Behavior Therapy (DBT) (Linehan 1993 ), which was developed for individuals diagnosed with borderline personality disorder (BPD). The emotional dysregulation that is the hallmark of BPD is also associated with symptoms of complex-PTSD (DESNOS). The treatment combines group skill training sessions, individual psychotherapy, and phone coaching. It is designed to help individuals label and regulate arousal, tolerate emotional distress, and trust their emotional reactions. Emotional regulation, interpersonal effectiveness, and self-management skills, including mindfulness and meditation skills are core skills in DBT. Validation and dialectical strategies are used to balance acceptance and change during treatment.

A different treatment model found to be effective in treating traumatized adults is Eye Movement Desensitization and Reprocessing (EMDR) (Shapiro 1995 ). For many traumatized individuals, remembering an event can feel as real as if it were happening again before their eyes. EMDR uses the person’s eye movements to help the natural processing and relaxation mechanisms available in the brain. During treatment, people are asked to think of a picture, emotion or thought relating to their trauma and at the same time to watch the therapist’s moving finger or listen to a repeating sound of a drum or a bell, leading to cognitive dissonance and a diminished power of the intrusive traumatic memory. EMDR can be delivered in a short series of sessions and does not involve detailed narrative of the traumatic event.

Narrative Therapy

This approach is based on the belief that trauma disrupts the normal narrative processing of everyday experiences by interfering with psychophysiological coordination, cognitive processes, and social connections, and such incomplete narrative leads to symptoms of posttraumatic distress (Wigren 1994 ). Narrative therapy thus allows for the completion and reframing of the traumatic event. While there is some evidence showing the effectiveness of this approach (Amir et al. 1998 ; Schaal et al. 2009 ), there seems to be no single narrative treatment model. Further research is needed in order to identify the best narrative approaches.

Group Therapy

While group therapy has been found to be effective at providing support for individuals in many circumstances, the use of certain group approaches, such as Critical Incidence Stress Debriefing (CISD) has been shown to have the potential for retraumatization. This is a particular danger for some individuals who are mandated to participate in such a group and listen to other people’s stories of their traumatic events before they had a chance to process their own trauma (Rose et al. 2002 ). Thus caution must be taken when utilizing any group approaches to trauma treatment.

One highly effective treatment model, used mainly in group settings, is Seeking Safety , developed by Lisa Najavitis ( 2006 ), The Seeking Safety Model is a present-focused therapy to help people attain safety from both trauma/PTSD and substance abuse. Treatment is flexible and utilizes 25 different topics that focus on both cognitive and behavioral areas. Seeking Safety is based on five central ideas: Safety as the priority of treatment; integrated treatment of trauma and substance use; a focus on ideals; content addressing cognitive, behavioral, interpersonal skills and case management; and attention to the clinician. Originally developed as an empowerment model for women, it is now recognized as being an effective and widely used approach for many others, including traumatized US veterans (Boden et al. 2012 ). The program focuses on teaching traumatized individuals to view themselves in more positive ways and helping clients build their self-esteem and self-confidence.

Medications

While there are no medications specific for trauma or PTSD, some medications have been shown to be effective at treating certain symptoms of PTSD, such as depression, anxiety or sleeping disorders. Currently the US Federal Drug Administration (FDA) has approved only two anti-depression medications for use with patients diagnosed with PTSD: sertraline (Zoloft) and paroxetine (Paxil), although other medications are being used off-label (Jeffreys 2013 ). It is worth noting that some medications have been found to be dangerous for those using or recovering from a substance use disorder, or those who are potentially suicidal (for a full review of medication use for those with PTSD, see Jeffreys 2013 ).

In general, when working with traumatized adults, the most important task is the establishment and maintenance of a physical and emotional sense of safety. It is critical to determine if the individual is at risk for imminent interpersonal violence or other maltreatment in their psychosocial environment, if they are suicidal or homicidal, and if they are psychologically stable and capable of caring for themselves (Briere and Scott 2012 ).

Interventions with Older Adults

While there is a growing acknowledgement of the need for psychosocial interventions with this population, the literature tends to focus more on programs and policies devoted to identification and reporting of elder abuse than actual clinical interventions (Brandler 2004 , Donovan and Regehr 2010 ). Literature on empirically supported interventions with traumatized older adults seems to be almost non-existent, although some believe that CBT may be effective (Foa et al. 2009 ). Obviously, more needs to be done to identify effective clinical approaches to this growing population.

Unfortunately, traumatized children and adults comprise a significant number of individuals in our communities and will continue to be with us in the foreseeable future. Many remain untreated. It is therefore critical for clinicians to be familiar with the various traumas encountered by individuals, families and communities, and to become knowledgeable about the most effective treatment approaches for a given population. Despite the growing research that is providing us with a base of scientific knowledge regarding promising interventions, there is much to be learned about effective interventions with traumatized children and adults—to make sure that we “do no harm.” Particularly important is research focusing on the resilience that many traumatized individuals’ exhibit and learning how best to encourage clients to access their strengths and abilities both in and out of the treatment process. Finally, because of the risk of experiencing secondary trauma, clinicians also need to be aware of the risk of working with high caseloads of traumatized individuals and to learn to take care of themselves so that they do not become part of the problem, but are an effective part of the solution.

While this article discusses the available research focusing on trauma among individuals with traditional gender identities, the authors recognize that transgender individuals experience disproportionate levels of trauma. Since a comprehensive discussion on this topic is beyond the scope of this paper, readers are referred to Mizock and Lewis ( 2008 ) for further information.

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Acknowledgments

This paper is based on a keynote presentation by the senior author at the international conference on Trauma Through The Life Cycle From a Strengths Perspective: An International Dialogue, Hebrew University, Jerusalem, January 8, 2012. The authors would like to thank Drs. April Naturale, Miriam Schiff and Shlomo Einstein for their helpful critiques of an earlier draft of this paper.

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Straussner, S.L.A., Calnan, A.J. Trauma Through the Life Cycle: A Review of Current Literature. Clin Soc Work J 42 , 323–335 (2014). https://doi.org/10.1007/s10615-014-0496-z

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Childhood trauma and adult mental disorder: A systematic review and meta-analysis of longitudinal cohort studies

Affiliations.

  • 1 Department of Psychology, Royal College of Surgeons in Ireland, Dublin, Ireland.
  • 2 Department of Psychiatry, Beaumont Hospital, Dublin, Ireland.
  • 3 Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland.
  • 4 Health Service Executive, Dublin, Ireland.
  • 5 Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.
  • PMID: 33315268
  • DOI: 10.1111/acps.13268

Objective: To systematically review evidence for the association between trauma experienced in childhood or adolescence, and the subsequent experience of affective or psychotic mental disorders in adulthood.

Methods: Electronic databases (Scopus, Medline (for Ovid), EMBASE and PsychINFO) were searched for peer-reviewed, longitudinal cohort studies in the English language examining child or adolescent exposure to trauma, and adult-diagnosed depression, anxiety, psychotic disorder or bipolar disorder. A total of 23 manuscripts were retained.

Results: Results revealed a significant association between the following childhood exposures and adult mental disorder: bullying (victimhood, perpetration and frequency); emotional abuse; physical neglect; parental loss; and general maltreatment (unspecified and/or multiple trauma exposure). There was some evidence of a dose-response relationship with those exposed to multiple forms of maltreatment having more than three times the odds of developing a mental disorder (Odds ratio = 3.11, 95% CI = 1.36-7.14). There was no significant association found between physical or sexual abuse and adult mental disorder; however, this is likely an artefact of how these adversities were assessed.

Conclusion: There is strong evidence of an association between childhood trauma and later mental illness. This association is particularly evident for exposure to bullying, emotional abuse, maltreatment and parental loss. The evidence suggests that childhood and adolescence are an important time for risk for later mental illness, and an important period in which to focus intervention strategies.

Keywords: bullying; child or adolescent abuse; child or adolescent maltreatment; mental disorder; parental loss; risk factor.

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review
  • Adult Survivors of Child Abuse*
  • Anxiety Disorders
  • Child Abuse*
  • Cohort Studies
  • Longitudinal Studies
  • Psychotic Disorders*

Grants and funding

  • G9815508/MRC_/Medical Research Council/United Kingdom
  • MC_PC_15018/MRC_/Medical Research Council/United Kingdom
  • MC_PC_19009/MRC_/Medical Research Council/United Kingdom
  • Open access
  • Published: 14 September 2022

Trauma-informed care in the UK: where are we? A qualitative study of health policies and professional perspectives

  • Elizabeth Emsley 1 ,
  • Joshua Smith 1 ,
  • David Martin 2 &
  • Natalia V. Lewis 3  

BMC Health Services Research volume  22 , Article number:  1164 ( 2022 ) Cite this article

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Trauma-informed (TI) approach is a framework for a system change intervention that transforms the organizational culture and practices to address the high prevalence and impact of trauma on patients and healthcare professionals, and prevents re-traumatization in healthcare services. Review of TI approaches in primary and community mental healthcare identified limited evidence for its effectiveness in the UK, however it is endorsed in various policies. This study aimed to investigate the UK-specific context through exploring how TI approaches are represented in health policies, and how they are understood and implemented by policy makers and healthcare professionals.

A qualitative study comprising of a document analysis of UK health policies followed by semi-structured interviews with key informants with direct experience of developing and implementing TI approaches. We used the Ready Extract Analyse Distil (READ) approach to guide policy document review, and the framework method to analyse data.

We analysed 24 documents and interviewed 11 professionals from healthcare organizations and local authorities. TI approach was included in national, regional and local policies, however, there was no UK- or NHS-wide strategy or legislation, nor funding commitment. Although documents and interviews provided differing interpretations of TI care, they were aligned in describing the integration of TI principles at the system level, contextual tailoring to each organization, and addressing varied challenges within health systems. TI care in the UK has had piecemeal implementation, with a nation-wide strategy and leadership visible in Scotland and Wales and more disjointed implementation in England. Professionals wanted enhanced coordination between organizations and regions. We identified factors affecting implementation of TI approaches at the level of organization (leadership, service user involvement, organizational culture, resource allocation, competing priorities) and wider context (government support, funding). Professionals had conflicting views on the future of TI approaches, however all agreed that government backing is essential for implementing policies into practice.

Conclusions

A coordinated, more centralized strategy and provision for TI healthcare, increased funding for evaluation, and education through professional networks about evidence-based TI health systems can contribute towards evidence-informed policies and implementation of TI approaches in the UK.

Peer Review reports

Individual, interpersonal and collective trauma is a highly prevalent and costly public health problem [ 1 ]. The WHO World Mental Health Survey identified that 70% of participants had experienced lifetime traumas, including physical violence, intimate partner sexual violence, and trauma related to war [ 2 ]. People experiencing socio-economic disadvantage, women, minoritized ethnic groups, and the LGBTQ + community are disproportionally affected by violence and trauma [ 3 , 4 ]. Adverse childhood experiences (ACEs) are stressful or traumatic events that occur during childhood or adolescence [ 5 ]. In England, a household survey found that nearly half of adults had experienced at least one ACE, including childhood sexual, physical or verbal abuse, as well as household domestic violence and abuse (DVA) [ 6 ]. DVA is considered to be a chronic and cumulative cause of complex trauma [ 7 ]. Up to 29% women and 13% men have experienced DVA in their lifetime, at a cost of £14 billion a year to the UK economy [ 7 , 8 , 9 ].

Cumulative trauma across the lifespan is associated with multiple health consequences [ 10 ]. The links between cumulative adversity from ACEs, DVA and other traumatic experiences are explained within the ecobiodevelopmental framework and the concept of toxic stress [ 11 ]. In a systematic review and meta-analysis of 37 observational studies of health behaviours and adult disease, patients with four or more ACEs were at higher risk of a range of poorer health outcomes including cardiovascular disease and mental ill health, versus those with no ACEs history [ 12 ]. Individuals and families who have experienced violence and trauma seek support from healthcare and other services for the physical, psychological and socioeconomic consequences of trauma [ 1 , 13 ]. In the household survey in England and Wales, adults who had experienced four ACEs were twice as likely to attend their general practice repeatedly, compared with those with no ACEs history, and incidence of health service use rose as the ACEs experiences increased [ 14 ]. In a systematic review 47% of patients in mental health services had experienced physical abuse and 37% had experienced sexual abuse [ 15 ].

If the high prevalence and negative impacts of trauma are not recognised and addressed in healthcare services, there may be negative consequences for patients and healthcare professionals. Patients may not disclose trauma or recognise the impact of trauma on their health [ 16 ]. Patients may also be at risk of re-triggering and re-traumatization, for example by the removal of choice regarding treatment, judgemental responses following a disclosure of abuse, seclusion and restraint [ 17 , 18 , 19 ]. Re-traumatization within health services can affect both patients and members of staff, with the latter experiencing vicarious trauma [ 20 ]. The resulting chronic stress may impact on staff members’ ability to empathise and support others [ 21 ]. Many healthcare staff themselves have lived experience of trauma. A recent systematic review of healthcare professionals’ own experience of DVA, reported a pooled lifetime prevalence of 31.3% (95% CI [24.7%, 38.7%] [ 22 ].

Over last 20 years, several frameworks for a trauma-informed (TI) approach at the health systems level have been developed [ 13 , 17 , 23 , 24 , 25 , 26 , 27 , 28 ]. These frameworks aim to prevent re-traumatization in healthcare services and mitigate the high prevalence and negative effects of violence and trauma on patients and healthcare professionals. A TI approach (synonyms TI care, TI service system) starts from the assumption that every patient and healthcare professional could potentially have been affected by trauma [ 13 ]. By realising and recognising these experiences and their impacts, we can respond by providing services in a trauma-informed way to improve healthcare experience and outcomes for both patients and staff. The process of becoming a TI system is guided by key principles of safety, trust, peer support, collaboration, empowerment and cultural sensitivity [ 13 ]. The most cited frameworks for a system-level TI approach are those by Harris and Fallot [ 29 ], and the US Substance Abuse and Mental Health Services Administration (SAMHSA) [ 13 ]. These frameworks highlight that it is necessary to, firstly, change organizational culture and environments (organizational domain) and then change clinical practices (clinical domain) by incorporating the four TI assumptions and six TI principles throughout the ten implementation domains within a health system [ 13 ] . Other authors proposed similar constructs for the framework of TI approach, often using slightly differing terminology [ 29 , 30 ]. The authors consistently highlighted that the framework of TI approach is not a protocol but rather high-level guidance applicable to any human service system and should be tailored to the organizational and wider contexts. The process of becoming a TI system is described as a transformation journey rather than a one-off activity.

Despite a 20-year history of the TI approach framework, several reviews have found limited evidence for their effectiveness in health systems, with most studies conducted in North America and only one qualitative study in the UK [ 31 , 32 , 33 ]. Despite little evidence of acceptability, effectiveness, and cost effectiveness in the UK context, policies and guidelines at national, regional and organisational levels recommend implementing TI approaches in healthcare organisations and systems. It is important to understand how TI approaches are being introduced into policy documents, and how these policies are being interpreted and applied within UK healthcare. This study aims to understand the UK-specific context for implementing a TI approach in healthcare by exploring:

How are TI approaches represented in UK health policies?

How are TI approaches understood by policy makers and healthcare professionals?

How are TI approaches implemented in the UK?

This study of UK policy and practice will help us understand what TI approaches mean for policy makers and professionals to inform future UK-specific policy and TI approaches in healthcare.

To answer our research questions, and consider perspectives from different standpoints, we conducted a multi-method qualitative study comprised of a document analysis of UK health policies followed by semi-structured interviews with key informants. Document analysis explored how TI approaches are represented in UK health policy while interviews explored professional views on how they are understood and implemented. We used the Ready Extract Analyse Distil (READ) approach [ 34 ], to guide the review of health policies and the framework method [ 35 ], to analyse data. The framework method is suitable for applied health research conducted by multi-disciplinary teams with varied experiences of qualitative analysis.

Data collection

Data collection occurred between October 2020 and June 2021, with researchers and interviewees based in remote settings due to social distancing restrictions during the COVID-19 pandemic. Sample size was informed by the concept of information power [ 36 ], and restricted by the available funding and a tight timeline.

Document search

We defined policy as ‘a statement of the government’s position, intent or action’ [ 37 ], and considered this definition at the level of a nation, local authority or organization. Two researchers (EE, NVL) identified key policy and related contextual documents, which provided background information on TI approaches. We identified documents through: (i) searches for peer reviewed and grey literature in our earlier systematic review on TI primary care and community mental healthcare [ 31 ], (ii) snowballing of references from included documents, (iii) signposting by interview participants and experts in the field of TI care. Researchers retrieved documents meeting the inclusion criteria: adult healthcare, UK-focus and discussion of TI approaches. We excluded documents on child healthcare, trauma-specific interventions and non-UK focus.

Qualitative interviews

We conducted virtual semi-structured interviews with professionals at decision making levels who have direct experience of developing and implementing TI approaches in the UK healthcare system. We agreed to recruit up to 10 professionals from national and local governments and healthcare organisations. Researchers sent an expression of interest letter via email and Twitter to: (i) individuals and professional networks of policy makers, (ii) authors of included policy documents, (iii) individuals recommended by interview participants. Interested individuals contacted study researchers who checked their eligibility, sent participant information leaflets, answered questions, and arranged interviews with those eligible and willing to proceed. Interviews were conducted over the Zoom video call platform. Researchers obtained verbal informed consent, asked demographic questions, and followed a flexible topic guide to ensure primary issues were covered during all interviews but allowing participants to introduce unanticipated issues. The topic guide explored participant experiences of developing and implementing TI approaches and their views on how TI approaches have come to be represented in policy and implementation (Additional file 1 ). The interviews were audio-recorded with consent, professionally transcribed verbatim, and anonymised.

Data analysis started alongside data collection, to help refine and guide further data collection [ 35 ]. We followed the four-step READ approach to document review in health policy research: 1) ‘Ready your materials’ which involves agreeing the type and quantity of documents to analyse, 2) ‘Extract data’ whereby key document information such as basic data and concepts are organized, 3)’Analyse data’ when data is interpreted and findings are developed, 4) ‘Distil your findings’ which involves assessing whether there is sufficient data to answer the research question and findings are refined into a narrative [ 34 ].

In step one, two researchers (EE, NVL) agreed to use purposive sampling to gather 24 documents representing a broad range of document categories including primary legislation, parliamentary documents, NHS and Public Health England strategy and planning documents, service-user perspectives, evaluation reports, and guidance on ‘how to do’ TI approach [ 38 ]. EE ordered included documents chronologically. In step two, EE read and re-read all included documents and used a customized Excel form to extract data on document title, authors, year, source, objectives, target audience, focus, key messages, referenced evidence, policies/guidelines, and recommendations. During data extraction, researchers made notes about how each document answered the following questions: What is TI care? TI care for whom? Why TI care? EE and NVL met regularly to discuss preliminary ideas for analysis.

In step three, we imported all included documents and interview transcripts into NVivo R project and applied the framework method [ 35 ]. To address variability in definitions and terminology regarding TI approaches, we included key concepts from the well-known SAMHSA system-level framework [ 13 ], as a basis for our coding frame, for example the six TI principles. First, all researchers read four documents and two interview transcripts and independently manually coded text relevant to our research questions using a combination of inductive and deductive coding [ 39 ]. Deductive coding helped to identify concepts related to TI care, even if the document itself did not specifically use the “trauma-informed” term. The researchers then met to compare initial thematic codes and agree on a ‘working analytical framework’ which was imported into NVivo and applied to the documents and interviews transcripts. We refined the framework by adding and merging thematic codes identified subsequently, ran matrix coding queries by data sub-sets (documents, interviews), and combined codes into final analytical themes that answered our research questions. During the analysis stage, researchers met bi-weekly to finalise the dataset, develop and refine coding frame and themes. We wrote reflective diaries and analytical notes and discussed how our clinical backgrounds in general practice and psychiatry, and varied experiences of qualitative research, could have influenced the analysis.

In step four, we stopped document review when we reached the pre-specified number of documents and discussed common findings. First, we illustrated how TI approaches have developed in the UK over time by creating an integrated timeline with document publication dates, the years when interview participants began working in this area, and broader contextual factors from national news and related media. Then we integrated findings from the analysis of documents and interviews through three iterative cycles of developing final analytical themes cutting across documents and interviews. Researchers produced written accounts of the themes, and tables with illustrative quotes that explained how TI approaches have been represented in policy documents, understood, and implemented in the UK.

Policy documents

We identified 50 documents and selected 24 policy documents at national, local, and organizational levels. The remaining 26 documents provided context and a background on TI approaches. The documents included were published over nine years (2012–2021) and considered all UK nations, multiple sectors, government policy and service-user voices. The documents either mentioned a TI approach or discussed related concepts such as a patient choice and safety of services (Table 1 ).

Mirroring the historical development of TI approaches from mental health services [ 13 , 29 ], across both documents and interviews, mental health was the most referenced sector ( n  = 24), followed by women’s health ( n  = 11), healthcare for rough-sleepers ( n  = 7), primary care ( n  = 4) and major incident management ( n  = 1). The level of application of the TI approach varied from one organization [ 55 ], to a public health board [ 59 ], to NHS-wide [ 48 , 50 ]. The geographic coverage of policy documents ranged from UK wide ( n  = 10) to regional application ( n  = 24). Scotland emerged as a leading region with the TI knowledge and skills framework for the Scottish Workforce [ 25 ].

The timeline of TI approaches and related concepts in the UK showed a steady growth between 2012 and 2021 with parallel developments from top-down and bottom-up (Fig.  1 ).

figure 1

An integrated timeline of how TI approaches have developed in the UK. Document publication dates, the years when interview participants began working in this area, and broader contextual factors from national news and related media are captured. The number/s in each cell correspond to a document reference [ 6 , 13 , 17 , 25 , 28 , 29 , 30 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 57 , 58 , 59 , 60 ]

We identified few documents prior to 2012, with the Health and Social Care Act published in 2012. Although the Act did not specifically use the term TI care, it discussed related concepts of a greater voice for patients, enabling patient choice and safety of services. We found a noticeable clustering of documents in 2018 and 2019. Potential contributions could be the release of key contextual documents such as the US SAMHSA guidance and the National ACEs Study in the preceding years [ 13 , 14 ]. Other possible reasons could be the high-profile MeToo and Black Lives Matter movements and tragedies like Grenfell fire. Relevant news articles, including calls for rape victim support and professional training on trauma, came to the fore in 2018–2021. These events and activities have brought the issues of trauma, vulnerable populations, intersectionality, and racial justice to the foreground and may have helped achieve a focus on TI approaches as a responsive system-level framework.

In total, 21 professionals expressed interest, 2 did not have direct experience of TI approach at the system level, 8 did not respond by the deadline, 11 provided consent and were interviewed. Interviews lasted between 32 and 68 min (mean 52 min). We achieved a maximum variation sample representing diversity of gender (4 men, 7 women), organizations (public, private, third sector), professional role (frontline to leadership positions), and direct experience of developing and/or implementing TI approaches in healthcare (from 2 to 25 years). Most participants developed and implemented TI approaches in England, at the level of organizations and local authorities (Table 2 ).

Three out of ten interview participants had been involved in developing and implementing TI approaches prior to the release of the first document in 2012, with the rest becoming involved in 2017, just prior to the clustering of documents in 2018 and 2019 indicating a pivotal wave of popularity of the TI approach framework at this time. Participants explained that their clinical practice facilitated interest in the topic.

Our framework analysis has produced three analytical themes with seven sub-themes:

How TI approaches are represented in UK health policies

How ti approaches are understood, ti care as different from other practices, ti care as a contextually tailored organizational approach.

TI care as a remedy to challenges;

How TI approaches are implemented

Piecemeal implementation and a need for a shared vision, factors that facilitated or hindered implementation, the evidence-policy gap, the future of ti care in the uk.

We found that the TI approach is referenced in government initiatives and included in policies at a national level, as well as in NHS and non-NHS organizations, local authorities, and devolved nations; however, there was no dedicated strategy or a position statement, nor was there an agreed terminology and framework, or a robust evidence base in the UK. Despite growing endorsement of TI approaches in policy documents (Fig.  1 ), positive statements at the national and NHS level were not backed up with legislation, guidance, funding commitment, and resource allocation.

We found divergent interpretations of a TI approach versus other concepts related to trauma, such as ACEs, psychologically informed environments and standard good clinical practice. One participant unified concepts such as TI care, ACEs and psychologically informed environments in recognising past traumatic experiences. Another participant detached the terms ACEs and TI care, reflecting that ACEs have become well known in research whereas a TI approach is a pragmatic way of supporting those who have experienced trauma. All documents and most participants clearly differentiated between a TI approach at the system level and standalone TI practices (e.g., routine enquiry about ACEs, one-off training about trauma). However, some participants considered standalone TI practices to be a TI approach. Documents and most interviewees differentiated TI approach from a good clinical practice by incorporation of the TI assumptions and principles [ 25 ].

In line with the SAMHSA guidance [ 13 ], document and interview data showed that the framework of a TI approach needs to be tailored to the organizational and wider context. Policy documents advised organizations to clarify what TI care means for them, and that application of the framework should depend on the needs of service users and organisations [ 25 , 28 , 52 , 54 , 59 , 60 ]. Several documents suggested that this organizational tailoring should be informed by service-users through co-production and co-design of services [ 17 , 28 , 49 , 52 , 53 , 54 , 55 , 60 , 61 ].

TI care as a remedy to challenges

In all policy documents and in nine interviews, TI approaches were presented as a remedy to a variety of problems within health systems. Sixteen of twenty-five documents justified a TI approach as a way for addressing the high prevalence and negative impact of violence and trauma on patients, with eleven documents considering its impact on staff. The growing international evidence base for the impact of psychological trauma and the need for service response was used in documents and interviews to justify TI approaches as a pragmatic solution to these concerns. However, the documents and interview participants justified the need for TI care by citing US and Welsh epidemiological studies on ACEs, DVA and patient accounts of being re-traumatized in services. We found no references to intervention studies that demonstrated effectiveness, cost-effectiveness, or acceptability of TI approaches in the UK.

In the NHS Long Term Plan, TI care was also identified as a component of a new model of integrated care [ 50 ]. A TI approach has also been presented as a solution to addressing the collective trauma of the COVID-19 pandemic for patients and staff [ 62 ].

Interviewees confirmed the piecemeal implementation of TI approaches in the UK and felt that a shared national vision would be beneficial. Participants agreed that the implementation of TI approaches varied across the UK, with Scotland having more strategic coordinated implementation (additional file 2 , quote 1). We found that different regions and organizations reinvented the TI approach wheel, with interviewees expressing a need for national coordination. Participants expressed the need for adequate allocated resources and a more unified approach across organizations and sectors as a solution to the patchy implementation in England (additional file 2 , quote 2). They gave examples of the bottom-up networking initiatives driven by experts in TI care who created opportunities for sharing best practice and resources for implementing TI approaches. Participants cited a UK-wide Trauma Informed Community of Action and local TI care working groups.

One participant from England suggested that whilst the SAMSHA definition of TI approach was widely cited, they did not feel there was an agreed set of components and activities for implementing the framework in practice. This participant felt that a consensus on shared practice standards was a necessary next step for TI care in the UK.

At the organization level, some participants felt high level leadership support was needed, and if lacking is a barrier to implementing a TI approach. To achieve effective implementation leaders with power and those with passion were felt to be important. The concept of organizational champions garnered support when “ champions act as influencers and their credibility within services adds to the potential for buy-in from other staff ”, fostering sustainable change [ 53 ]. One participant warned against a reliance on top-down leadership, explaining that when a senior leader leaves an organization’s priorities can change. The participant also felt that change driven from the top-down, might lead to resistance from front-line staff (additional file 2 , quote 3). Some interviewees reaffirmed the view that people with lived experience should be involved in leading implementation of TI approaches (additional file 2 , quote 4).

Some interviewees felt that passionate individuals alone cannot create effective change without support at the organization level (additional file 2 , quote 5). Collective responsibility and organizational commitment were highlighted as an essential factor to support individuals with passion. In contrast, unsupportive organizational culture and high-pressure environments was perceived as a barrier (additional file 2 , quote 6). One document cited scarcity of resources and low staff morale, as well as a resistance to new initiatives and upheaval [ 52 ]. Competing demands and opportunity costs were also raised (additional file 2 , quote 7).

At the wider context level, documents highlighted the value of political support capable of influencing practice nationally [ 17 ]. Some interviewees explained disconnected and decentralized implementation of TI approaches across the UK by a shortage of political will and leadership in the central UK government, compared with those of the devolved administrations in Scotland and Wales (additional file 2 , quote 8). Proposed explanations included smaller territories, populations and governments, and “ more of a left-leaning social conscience politics” (Participant 3). Another interviewee called for a united parliamentary leadership recognised by government and capable of influencing policy.

Inadequate funding and commissioning of services was also described as a barrier, partly explaining regional differences in implementation of TI care (additional file 2 , quote 9). The COVID-19 pandemic was perceived as a barrier that contributed to the backlog of initiatives and work in the pipeline (additional file 2 , quote 10).

UK policies on implementation of TI approaches were not supported by UK-specific, methodologically robust, evidence for effectiveness, cost effectiveness and acceptability. Participants explained the policy-evidence gap by citing methodological challenges of evaluating system-level transformation and a need for commitment from commissioners and funders (additional file 2 , quote 11). In addition, participants who developed and implemented TI approaches in their organizations and regions did not have the capacity to evaluate their initiatives and disseminate the findings (additional file 2 , quote 12).

Participants had differing views on the future of TI care in the UK, although most agreed on its permanency. Some interviewees felt that TI approaches have already gained a critical momentum in the UK. In contrast to comments about TI care as a passing trend or ‘buzzword’ in the absence of in depth understanding, several interviewees voiced confidence that TI approach is here to stay, and will evolve, being incorporated into policy as well as being adopted more widely. Others were less optimistic and were concerned that insufficient political backing means policy endorsement will not translate to meaningful practice change.

Some participants thought that TI care should become a mandatory consideration with stronger central policy or monitoring by national watchdogs. They felt that the support of additional nation-wide regulatory measures could be beneficial. In contrast, some interviewees showed scepticism, fearing the creation of further ‘box-ticking’ measures. They feared that efforts to police or monitor providers could create a burden of empty bureaucracy without improving practice (additional file 2 , quote 13).

Our document analysis of health policies and interviews with professionals found differing representation, understanding, and implementation of TI approaches in the UK with wide variations between geographical areas, services, and individual professionals. Cross-sectoral endorsement of TI approaches in policies was not supported by high-level legislation or funding, and a UK-specific evidence base. Despite divergent and conflicting interpretations of TI approaches, the common understanding was that it differs from other practices by integrating TI principles at the organisational level and it should be tailored to the organization and wider contexts. It can also address NHS problems from integrated care to post-COVID recovery. We found more centralized implementation of TI approaches in Scotland and Wales versus piecemeal implementation in England. The implementation of TI approaches in England was driven from the bottom-up by passionate dedicated leaders at the level of organization or local authority, who called for more coordinated working supported by the UK government and NHS leaders. We identified factors that facilitated or hindered implementation of TI approaches at the level of organization (leadership, service user involvement, organizational culture, resource allocation, competing priorities) and wider context (government support, funding). The evidence-policy gap in TI care implementation can be explained by limited funding and evaluation capacity. Professionals had differing views on the future of TI approaches, however all agreed that without political backing at the government level, policy endorsement will not translate into meaningful implementation.

Our finding of a marked difference in the landscape of TI approaches in healthcare systems between the devolved nations, with evidence of a unified national strategy emerging in Scotland and Wales and notably absent in England could have several explanations. These include smaller territories, populations, and governments in devolved nations, with clear buy-in from government-level leadership in Scotland. Our analysis highlighted the initiatives of local decision-makers in England who have developed and implemented TI approaches in their own organizations and local authorities. The absence of a national strategy in England contributed to the piecemeal implementation, with some regions leading the way, and others silent. As local TI leads have been left to ‘find their own way’, they may not always have been aware of similar initiatives in other organizations and regions. A proposed solution was bottom-up initiatives aiming to bring the local TI leads together to share resources and good practice. This finding indicates the need for a leader on TI approaches within or linked to the UK government who can support and strengthen the bottom-up initiatives.

Another important finding is confirmation of the evidence-policy gap, with proposed reasons emerging in the analysis. Interview participants explained an absence of UK evidence on the effectiveness of TI approaches by a need for more interest from commissioners and funders, as well as a lack of physical and methodological capacity to evaluate system-level TI approaches. The former can be resolved through funding calls and comprehensive, transparent evaluation. The latter can be addressed by funding evaluations and raising awareness regarding available methodologies and tools for evaluating TI system change interventions [ 32 , 33 ].

Our finding of differing understanding of TI-approaches is in line with prior literature [ 63 ]. We found that some participants interpreted standalone TI practices (e.g., ACEs enquiry, one-off training about TI care) as a TI approach. Such interpretations are not supported by evidence. Authors of the ACEs study explained that the ACEs score is not a diagnostic tool, therefore care should be taken if used as part of community-wide screening, with rigorous evaluation of its use [ 64 ]. Recent reviews also found limited evidence on outcomes from routine enquiry, recommending further research [ 65 , 66 ]. Several systematic reviews demonstrated that standalone awareness raising did not result in change in behaviour and practices among healthcare professionals [ 67 , 68 ].

These misunderstandings can be explained by the conceptual mutability of a TI approach framework, lack of awareness about existing frameworks, and a need for coordinated working led by experts in TI approaches. The evidence of emerging working groups and UK-wide professional networks on TI care is promising. However, these initiatives require adequate funding and coordination to sustain momentum and develop further. These professional networks can become the platform for education about evidence-based TI approaches contributing to increasing value and reducing waste in research and implementation in this field.

This study is methodologically robust with perspectives drawn from UK policy documents and professionals, who have direct experience of developing and implementing TI approaches. Data analysis occurred alongside data collection, to help refine and guide further data collection. The limitations include no professional informants from devolved nations and no participants at the level of UK government. Due to time and funding restrictions, we could only recruit 11 professionals and did not interview patients including those with lived experience of trauma. Our small sample size could have resulted in underrepresentation of views of some stakeholders. Future research should recruit informants from these groups to draw a complete picture of the landscape of TI approaches in the UK.

Although health policies endorse implementation of TI approaches in the UK, they do not provide specific legislation, strategy or funding and are not supported by evidence of effectiveness. Understanding and implementation of TI approaches varies between regions, organizations, and individual professionals; however, all agree that if implemented at the system level and contextually tailored, TI approaches can mitigate varied problems withing NHS. The implementation of TI approaches in the UK is driven by local experts in TI care. A coordinated, more centralized strategy and enhanced provisioning for TI healthcare, including increased funding for evaluation and education through TI professional networks, can contribute towards evidence-informed policies and implementation of TI approaches in the UK.

Availability of data and materials

Data are available at the University of Bristol data repository, data.bris, at  https://doi.org/10.5523/bris.2awc5pqkavac12d6jm1qp9wetm .

For reference: Lewis, N. (2022): TAPCARE policy review study.  https://doi.org/10.5523/bris.2awc5pqkavac12d6jm1qp9wetm

All methods were performed in accordance with relevant guidelines and regulations as detailed here: https://www.biomedcentral.com/getpublished/editorial-policies#research+involving+human+embryos%2C+gametes%2C+and+stem+cells .

Abbreviations

Adverse childhood experiences

Coronavirus disease

Domestic violence and abuse

National Health Service

Substance Abuse and Mental Health Services Administration

Trauma-informed

United Kingdom

United States of America

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Acknowledgements

We would like to thank all the interview participants and those with an interest in TI approaches who kindly shared policy documents and background literature with the study group. We would like to acknowledge the contributions of Dr Sandi Dheensa in reviewing the draft manuscript.

This report is independent research funded by the National institute for Health and Care Research (NIHR), Research Capability Funding stream via NHS Bristol, North Somerset and South Gloucestershire Clinical Commissioning Group. NVL was also supported by the NIHR Bristol Biomedical Research Centre (grant BRC-1215-20011). The views expressed are those of the authors and not necessarily those of the NHS, NIHR or the Department of Health and Social Care.

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NVL conceived, designed, and led the study. EE, NVL, JS and DM collected and analysed documents and interview data. EE and NVL wrote the first draft of the manuscript with input from DM and JS. All authors contributed to subsequent revision and approved the final version.

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Analytical themes with subthemes and supporting quotes.

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Emsley, E., Smith, J., Martin, D. et al. Trauma-informed care in the UK: where are we? A qualitative study of health policies and professional perspectives. BMC Health Serv Res 22 , 1164 (2022). https://doi.org/10.1186/s12913-022-08461-w

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research paper about trauma

Trauma and Stress

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  • Traumatic experiences are associated with substance use and with developing substance use disorders. Violence, abuse, neglect, and family or social conflict are among the traumatic events and circumstances that are linked with the risk of developing a substance use disorder.
  • Children and adolescents who experience trauma are particularly susceptible to developing a substance use disorder later in life. Many people who have been diagnosed with post-traumatic stress disorder (PTSD) also have a substance use disorder.
  • There are effective treatments for trauma-related mental health disorders. NIDA supports research to better understand the impact of trauma and chronic stress on the risk of developing a substance use disorder, and on how to prevent that outcome.

What is stress? What is trauma?

Stress is an emotional or physical reaction to a challenge or demand, such as school demands, financial problems, or having an illness. A stressor may be a one-time or short-term occurrence, or it can happen repeatedly over a long time.

When a person is under stress, the body reacts by releasing hormones that produce the “fight or flight” response. Heart rate, breathing rate, and blood pressure go up. Occasional stress is a normal coping mechanism. However, long-term stress (also called chronic stress) may contribute to or worsen a range of health problems including digestive disorders, headaches, sleep disorders, and other symptoms. 

Trauma refers to a persistent emotional response to an event, series of events, or circumstances that an individual experiences as harmful or threatening. It can result in heightened stress and other lasting adverse impacts on a person’s functioning and well-being.

A traumatic event is a shocking, scary, or dangerous experience. Experiences like natural disasters (such as hurricanes, earthquakes, and floods), acts of violence (such as assault, abuse, terrorist attacks, and mass shootings), as well as car crashes and other accidents can all be traumatic. Traumatic circumstances can include neglect, loss of a parent or companion, family conflict, racism, and discrimination. In some cases, emotional responses to traumatic events or circumstances continue for a long period of time and interfere with everyday life, a condition known as post-traumatic stress disorder (PTSD) . Stress and trauma may contribute to mental health disorders such as depression and anxiety, and to substance use and its progression to substance use disorders.

How does trauma affect a person’s brain and body?

A person’s experiences over a lifetime are a factor in their brain structure and function. Experiencing abuse or neglect, separation from or loss of a parent or companion, being a victim of violence or bullying, going to war, or experiencing racism or discrimination, among many other events and circumstances, can cause changes in the brain that make a person more sensitive to future events, even daily life stress. 

As a result, a trauma survivor may be more sensitive to and less able to cope with stress in everyday life. Most people will recover from these symptoms, and their reactions will lessen over time. In some cases, these responses continue for a longer period of time and interfere with everyday life, a condition known as post-traumatic stress disorder (PTSD) .

What is the connection between trauma, stress, and substance use disorders?

Studies show traumatic, extremely stressful experiences like abuse, violence, neglect, or the death of a loved one make a person more vulnerable to developing a substance use disorder.  Someone who has been through trauma or has experienced chronic stress might use substances like drugs and alcohol as a form of self-medication. They may use substances to temporarily cope with the distress they feel or with symptoms of related mental illnesses like post-traumatic stress disorder (PTSD) .

Traumatic stress can also cause changes to a person’s brain function and their behavior, making it more likely that substance use will lead to an addiction. This is particularly true in early life: Research shows that experiencing adverse childhood experiences (ACEs) like violence, abuse, neglect, or other early-life stressors is associated with a greater likelihood of developing substance use disorders later in life.

Severe or chronic stress can also affect brain circuits that are involved in reward, motivation, and learning; stress can also increase someone’s craving and decrease their ability to control how they respond to impulses. Addiction affects these same brain processes, which is another reason why researchers think stress increases vulnerability to addiction or relapse, which is when someone who has been abstinent starts to use substances again. Research also shows that having addiction makes stress symptoms worse. 

Does trauma always lead to developing a substance use disorder?

Not everyone who experiences trauma will develop an addiction. Genetics, environment, family history of addiction, severity of trauma, childhood adversity, and history of past drug use are all factors contributing to a person’s risk of developing a substance use disorder.

Protective factors such as individual traits like optimism and environmental influences like healthy family and peer relationships, as well as targeted prevention interventions, can reduce the risk of developing a substance use disorder. Read more about preventing substance use and substance use disorders .

How is trauma linked to PTSD and other mental illnesses?

About 8% of people who have experienced trauma go on to develop PTSD in the course of their lifetime. 1  A person with PTSD has repeated disturbing thoughts and flashbacks of a dangerous, shocking, or scary event. They may often feel afraid, anxious, angry, or ashamed.

Research shows that there is a big overlap between people who have PTSD and those who develop substance use disorders, and many people are diagnosed with both at some point. People with both disorders have more chronic physical health problems, more social problems, and an increased risk of violence or suicide.

A person may also develop other mental health disorders like depression or anxiety after experiencing trauma. These problems are also associated with addiction. In fact, per an analysis of a national survey published in 2017, 3.3% of the US adult population, or 7.7 million adults, had co-occurring disorders during the 12 months before the survey interview. 2  

What is the relationship between trauma and substance use disorders?

Physical and sexual abuse.

In one survey of more than 600 people with a substance use disorder, almost half reported suffering physical or sexual abuse, with women reporting much higher rates of both. 3  Such abuse presents even greater potential harm for children. People with a history of childhood physical or sexual abuse have, respectively, a 74% and 73% greater risk of developing a substance use disorder in their lifetime than other people. 4

People who are the victim of or who witness violence have an increased risk of substance use and misuse. Exposure to interpersonal or intimate partner violence is associated with a risk of substance use and a progression to substance use disorder, particularly for women. Military life is also linked with substance use problems, though military personnel who have had multiple deployments, combat exposure, and combat-related injuries are at greater risk of developing an addiction. Further, many studies show an increase in alcohol, drug use, or smoking following acts of terrorism.

Family Conflict

Parental divorce and conflict, loss of a parent, or poor family relationships contribute to severe, chronic stress that can increase someone’s vulnerability to addiction.

Racism and Systemic Discrimination

Experiencing prejudice and stigma, including racial and ethnic discrimination, can also cause chronic stress, raising the risk of substance use and misuse. Research suggests that people who feel discriminated against because of their gender identity also have a higher risk of substance misuse.

Physical Injury

A serious head injury, particularly in children and adolescents, is associated with a higher risk of addiction. Researchers suspect that a severe injury may disrupt parts of the brain involved with making decisions and controlling impulses.

Are there treatments for people with substance use disorders who have another mental health disorder?

When someone has a substance use disorder and another mental health disorder, it is usually better to treat them at the same time rather than separately. Some research suggests that this can increase treatment effectiveness for both disorders. For example, in one NIDA-funded study, people who received a treatment called prolonged exposure therapy for PTSD along with treatment for a substance use disorder had more improvement in PTSD symptoms than people who received treatment for addiction alone. 5  As a best practice, health providers should screen for past trauma when providing care for substance use disorders, given the high rate of people who experience both. 6

See more information about co-occurring substance use and mental health disorders on the National Institute of Mental Health website.

Why does NIDA support research on trauma and substance use disorders?

NIDA supports research to better understand the impact of trauma and chronic stress on the risk of developing a substance use disorder, and on how to prevent that outcome.

For example, NIDA plays a leading role in the Adolescent Brain Cognitive Development® (ABCD) Study , the largest long-term study of brain development and child health ever conducted in the United States. This project will increase our understanding of environmental, social, genetic, and other biological factors that affect brain and cognitive development and that can enhance or disrupt a young person’s life trajectory.

NIDA also supports and funds research, often working with partners at the National Institutes of Health, on effective treatments for substance use disorders in people who have experienced trauma.

Latest from NIDA

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Semaglutide associated with lower risk of suicidal ideations compared to other treatments prescribed for obesity or type 2 diabetes

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The power of protective layers: Employers advancing whole-person health

A diverse group of six children making environmental art outdoors with an adult.

Anti-poverty programs may help reduce disparities in brain development and mental health symptoms in children

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Tobacco smoking rates are decreasing in people with major depression and substance use disorder

Learn more about trauma, stress, and substance use disorders.

  • Read more about Substance Use and Co-Occurring Mental Disorders on the National Institute of Mental Health (NIMH) website.
  • See information Coping with Traumatic Events on the NIMH website.
  • See NIH Experts Discuss the Intersection of Suicide and Substance Use : Learn about common risk factors, populations at elevated risk, suicides by drug overdose, treatments, prevention, and resources for finding help.
  • Find a treatment center near you on the Substance Abuse and Mental Health Services Administration (SAMHSA) website.
  • Kilpatrick DG, Resnick HS, Milanak ME, Miller MW, Keyes KM, Friedman MJ. National estimates of exposure to traumatic events and PTSD prevalence using DSM-IV and DSM-5 criteria . J Trauma Stress . 2013;26(5):537-547. doi:10.1002/jts.21848
  • Han B, Compton WM, Blanco C, Colpe LJ. Prevalence, Treatment, And Unmet Treatment Needs Of US Adults With Mental Health And Substance Use Disorders . Health Aff (Millwood) . 2017;36(10):1739-1747. doi:10.1377/hlthaff.2017.0584
  • Keyser-Marcus L, Alvanzo A, Rieckmann T, et al. Trauma, gender, and mental health symptoms in individuals with substance use disorders . J Interpers Violence . 2015;30(1):3-24. doi:10.1177/0886260514532523
  • Halpern S. Child Maltreatment and Illicit Substance Abuse: A Systematic Review and Meta-Analysis of Longitudinal Studies . Child Abuse Review . Published online November 18, 2018. doi:https://doi.org/10.1002/car.2534
  • Ruglass LM, Lopez-Castro T, Papini S, Killeen T, Back SE, Hien DA. Concurrent Treatment with Prolonged Exposure for Co-Occurring Full or Subthreshold Posttraumatic Stress Disorder and Substance Use Disorders: A Randomized Clinical Trial . Psychother Psychosom . 2017;86(3):150-161. doi:10.1159/000462977
  • Center for Substance Abuse Treatment (US). Trauma-Informed Care in Behavioral Health Services . Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2014. (Treatment Improvement Protocol (TIP) Series, No. 57.) Chapter 4, Screening and Assessment. Available from: https://www.ncbi.nlm.nih.gov/sites/books/NBK207188/

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“The Biological Effects of Childhood Trauma”

I. synopsis.

Trauma in childhood is a grave psychosocial, medical, and public policy problem that has serious consequences for its victims and for society. Chronic interpersonal violence in children is common worldwide. Developmental traumatology, the systemic investigation of the psychiatric and psychobiological effects of chronic overwhelming stress on the developing child, provides a framework and principles when empirically examining the neurobiological effects of pediatric trauma.

Despite the widespread prevalence of childhood trauma, less is known about trauma's biological effects in children as compared to adults with child trauma histories; and even less is known about how these pediatric mechanisms underlie trauma's short-term and long-term medical and mental health consequences. This article focuses primarily on the peer-reviewed literature on the neurobiological sequelae of childhood trauma in children and adults with histories of childhood trauma. We also review relevant studies of animal models of stress to help us better understand the psychobiological effects of trauma during development. Next, we review the neurobiology of trauma, its clinical applications and the biomarkers that may provide important tools for clinicians and researchers, both as predictors of posttraumatic stress symptoms and as useful tools to monitor treatment response. Finally, we offer suggestions for future researchers.

III. Introduction

Trauma in childhood has serious consequences for its victims and for society. For the purposes of this critical review, childhood trauma is defined according to the Diagnostic and Statistical Manual of Mental Disorders IV and V as exposure to actual or threatened death, serious injury, or sexual violence [ 1 , 2 ]. This includes experiences of direct trauma exposure, witnessing trauma or learning about trauma that happened to a close friend or relative. In children, motor vehicle accidents, bullying, terrorism, exposure to war, child maltreatment (physical, sexual, and emotional abuse; neglect) and exposure to domestic and community violence are common types of childhood traumas that result in distress, posttraumatic stress disorder (PTSD), and posttraumatic stress symptoms (PTSS). Childhood traumas, particularly those that are interpersonal, intentional, and chronic are associated with greater rates of PTSD [ 3 ], PTSS [ 4 , 5 ], depression [ 6 ] and anxiety [ 7 ], antisocial behaviors [ 8 ] and greater risk for alcohol and substance use disorders [ 9 - 12 ].

The traditional categorical cluster of symptoms that form the diagnosis of PTSD are each associated with differences in biological stress symptoms and brain structure and function; and are thought to individually contribute to delays in or deficits of multisystem developmental achievements in behavioral, cognitive and emotional regulation in traumatized children and lead to PTSS and co-morbidity [ 13 ]. Thus, we examine PTSD as a dimensional diagnosis encompassing a range of pathological reactions to severe stress, rather than as a dichotomous variable.

Developmental traumatology, the systemic investigation of the psychiatric and psychobiological effects of chronic overwhelming stress on the developing child, provides the framework used in this critical review of the biological effects of pediatric trauma.[ 13 ] This field builds on foundations of developmental psychopathology, developmental neuroscience, and stress and trauma research. The DSM-IV-TR diagnosis of PTSD is made when criterion A, a Type A trauma, is experienced and when three clusters of categorical symptoms are present for more than one month after the traumatic event(s). These three clusters are Criterion B: intrusive reexperiencing of the trauma(s), Criterion C: persistent avoidance of stimuli associated with the trauma(s), and Criterion D: persistent symptoms of increased physiological arousal.[ 1 ] These criteria are complex and each Criterion is thought to be associated with dysregulation of at least one major biological stress system as well as several different brain circuits. This makes both the psychotherapeutic and the psychopharmacological treatment of individuals with early trauma complex and challenging.

Criterion symptoms have an experimental basis in classical and operant conditioning theory, where animals learn to generalized behaviors based on previous experiences or “reinforcements”[ 14 ] and in animal models of learned helplessness where animals under conditions of uncontrollable shock do not learn escape behaviors, and have exaggerated fear responses as well as social isolation and poor health [ 15 ]. For example, Cluster B reexperiencing and intrusive symptoms can best be conceptualized as a classically conditioned response that is mediated by the serotonin system and is similar in some ways to the recurrent intrusive thoughts experienced in obsessive compulsive disorder, where serotonin and norepinephrine transmitter deficits play an important role [ 16 ]. An external or internal conditioned stimulus (e.g., the traumatic trigger) activates unwanted and distressing recurrent and intrusive memories of the traumatic experience(s) (e.g., the unconditioned stimulus). However, other Criterion B symptoms, such as nightmares or night terrors, may involve the dysregulation of multiple neurotransmitter systems (serotonin, norepinephrine, dopamine, choline, gamma-amino butyric acid (GABA) [ 17 ]). Criterion C symptoms represent both avoidant behaviors and negative alterations in cognitions. In the DSM-V, Criterion C was divided into avoidant behaviors and Criterion D negative alterations in cognitions [ 2 ]. Avoidant behaviors can be thought of as ways to control painful and distressing reexperiencing of symptoms. These symptoms are likely associated with the dopamine system and overactivation of the opioid system and associated with anhedonia and numbing of responses [ 18 ]. In the DSM-IV the former Criterion D persistent symptoms of increased physiological arousal and reactivity is now Criterion E, and likely involves dysregulation of several biological stress systems [ 13 , 19 ] as discussed in further detail below.

We will review the known differences in pediatric victims’ stress biology compared to those children who have not experienced trauma. These differences are likely the causes of the greater rates of psychopathology (PTSD, depression, disruptive behaviors, suicidality, substance use disorders) and of the common medical disorders (cardiovascular disease, obesity, chronic pain syndromes, gastrointestinal disorders, immune dysregulation) seen in child victims [ 20 ]. Throughout, we will associate the relationship to biological stress systems and common stress symptoms. On many levels, childhood trauma can be regarded as “an environmentally induced complex developmental disorder”[ 13 ].

Exposure to a traumatic event or series of chronic traumatic events (e.g., child maltreatment) activates the body's biological stress response systems [ 21 - 23 ]. Stress activation has behavioral and emotional effects that are similar to individual PTSS symptoms [ 24 ]. Further, an individual's biological stress response system is made up of different, interacting systems, that work together to direct the body's attention toward protecting the individual against environmental life threats and to shift metabolic resources away from homeostasis and toward a “fight or flight” (and/or freezing) reaction [ 19 , 25 ]. The stressors associated with the traumatic event are processed by the body's sensory systems through the brain's thalamus, which then activates the amygdala, a central component of the brain's fear detection and anxiety circuits. Cortisol levels become elevated through transmission of fear signals to neurons in the prefrontal cortex, hypothalamus, and hippocampus, and activity increases in the locus coeruleus and sympathetic nervous system. Subsequent changes in, catecholamine levels contribute to changes in heart rate, metabolic rate, blood pressure, and alertness [ 19 ]. This process also leads to the activation of other biological stress systems.

In the review of the pertinent literature section, we will review the main biological stress response systems. We will focus on the limbic-hypothalamic-pituitary-adrenal (LHPA) axis, and the locus coeruleus-norepinephrine/sympathetic nervous system (SNS) or catecholamine system. We will also review the serotonin system, oxytocin and the oxytocin system, the immune system, and new data in genetic and epigenetic factors and gene-environment interactions that influence these systems and contribute to an individual's experience of vulnerability and resilience to childhood trauma. For each of these systems, we will provide an explanation of the mechanisms that drive them, followed by an examination of how these systems compare in children and adults who have been exposed to childhood trauma, thereby highlighting how early life adversity can disrupt the body's ability to regulate its response to stress.

Experiencing trauma during development along with dysregulation of biological stress systems can adversely impact childhood brain development [ 13 ] and we will discuss brain imaging studies in children who experienced trauma and adults with trauma histories. Recently, the field of neuroscience has become increasingly aware of gender as an important moderator of experience, so throughout, we review peer reviewed publications that highlight gender differences, if available. Little is known about trauma's neurobiological, genetic, and epigenetic effects in children as compared to adults with trauma histories. Since longitudinal psychobiological research in pediatric trauma is a severely understudied area, most of our review will be based on cross-sectional studies. Although we will highlight studies where longitudinal research is available, more longitudinal research in trauma-exposed children is needed to understand the pediatric mechanisms underlying trauma's short-term and long-term adverse effects in adolescence and adulthood. We will review the clinical applications of this knowledge and discuss how stress related biomarkers may provide important tools for clinicians and researchers to objectively examine predictors of PTSS and to monitor treatment response. We then offer suggestions for future directions.

A literature search of Pubmed and PsychInfo articles published to 2013 using keywords and MeSH terms “childhood,” “trauma,” “stress,” and/or “posttraumatic stress,” where crossed individually with “hypothalamic pituitary axis (HPA)”, “corticotrophin releasing hormone” corticotrophin releasing factor,” “immune,” “serotonin,” “dopamine,” “oxytocin,” “brain,”, “brain imaging,” “brain structure,” “brain function,” “cognitive,” “genes,” “polymorphisms,” and “epigenetics,” that were limited to the English language, were reviewed and selected for this critical review. Trauma studies involving physical head trauma or medical illnesses were not included. Our criteria were that the articles be peer-reviewed and methodologically sound, with emphasis placed on the paucity of longitudinal studies in this field. When reviews were needed to describe the foundations of biological stress systems and brain development, meta-analyses or peer-reviewed critical reviews published by known stress researchers were cited.

IV. Review of the pertinent literature: The Neurobiology of Biological Stress Systems Limbic-Hypothalamic-Pituitary-Adrenal (LHPA) Axis

The LHPA axis plays a central role in regulating the body's response to stress and is the most studied biological stress system in animals and humans. Activation of the LHPA axis triggers the hypothalamus to secrete corticotrophin releasing hormone (CRH). This neuropeptide, also called corticotrophin releasing factor (CRF), is a key mediator of the stress response [ 26 ]. The term CRH is used when describing its function in the neuroendocrine system and the term CRF is commonly used when describing its function as a neurotransmitter. However the term CRH is the older term and authors are not always consistent in using these rules. CRH stimulates the release of adrenocorticotrophic hormone (ACTH) by binding to CRH receptors in the anterior pituitary. ACTH in turn binds to G protein-coupled receptors in the adrenal cortex, especially in the zona fasciculata of the adrenal glands. ACTH also stimulates the secretion of cortisol, a glucocorticoid hormone that plays an important role throughout the central nervous system (CNS). Cortisol activates glucocorticoid and mineralocorticoid receptors, which are located and expressed throughout the brain. Glucocorticoid receptors act as transcription factors and regulate gene expression for metabolism and immune function, as well as for cognitive and brain development [ 27 ]. Increased levels of cortisol suppress the immune system, gluconeogenesis, and inhibit its own secretion via negative feedback to glucocorticoid receptors in the hippocampus [ 19 ].

CRF is widely distributed throughout the brain and is involved in the stress response and learning and memory [ 28 ]. Cortisol regulates the stress response system both in the hippocampus and medial prefrontal cortex (mPFC), where it works to attenuate the stress response, and in the medial and central nuclei of the amygdala, where it works to promote the stress response via CRF-1 receptors [ 29 ]. Through negative feedback, cortisol controls its own secretion, inhibiting the hypothalamus’ release of CRH and the pituitary's release of ACTH, thereby bringing the body back to a state of homeostasis rather than arousal[ 19 ]. Cortisol levels have a consistent diurnal pattern where levels are typically close to their peak during morning awakening, rise further in the 20-minute period after awakening and then progressively fall, reaching the nadir in the afternoon in children [ 30 ] adolescents [ 31 ], and adults [ 32 ]. Furthermore, cortisol levels and pituitary volumes increase with age [ 33 ].

The LHPA Axis and Childhood Trauma

Exposure to severe stress and trauma in youth can disrupt the regulatory processes of the LHPA axis across the life span in both animals and humans [ 26 , 27 , 34 - 36 ]. In animals, injections of CRF in early life produces a delayed effect in later life that is associated with reduced cognitive function, reduced number of number of CA3 hippocampal neurons, and decreased branching of hippocampal pyramidal neurons [ 37 , 38 ]. Although the pediatric trauma literature suggest that the LHPA system is dysregulated in youth exposed to trauma, the cortisol regulation data seem contradictory, where baseline morning and 24-hour cortisol concentrations showed no differences [ 39 , 40 ] , were higher [ 41 - 47 ] or in a few studies, lower[ 47 - 49 ] compared to youth without trauma. Additionally, no cortisol response differences [ 39 , 50 , 51 ], blunted cortisol responses[ 52 ], and increased cortisol concentration responses [ 53 , 54 ] have been reported in maltreated children and adults with histories of childhood maltreatment under psychological and pharmacological challenges. Other measures of the LHPA axis such as ACTH also show these contradictory findings where both blunted [ 39 , 55 ] and increased [ 50 , 53 , 54 , 56 ] ACTH levels have been reported in maltreated depressed children and adults with histories of childhood maltreatment under psychological and pharmacological challenges. Furthermore, in one meta-analysis, lower morning but higher afternoon/evening cortisol levels, a flatter diurnal rhythm, and greater daily cortisol output were seen in adults retrospectively reporting trauma[ 47 ]; while another meta-analysis demonstrated that individuals with adulthood trauma exposure and adults with PTSD showed no differences in cortisol levels [ 57 ], indicating that the developing LHPA axis is vulnerable to dysregulation as a result of childhood trauma.

As outlined by De Bellis [ 13 , 39 , 42 ] , the discrepant findings described above may be related to several mediator and moderator mechanisms. A detailed examination of the factors associated with these mechanisms is important in studies endophenotyping an individual's response to the effects of early trauma on the development of biological stress systems. Endophenotyping is a term which is used to describe emotional and behavioral symptoms into stable phenotypes or observable traits with genetic associations. Identifying endophenotypes in traumatized children will be an important new tool for novel approaches to treatments such as personalized medicine [ 58 ]. Several of these mediation and moderation mechanisms for the biological effects of trauma on the developing child can be found in a previously published critical review (i.e., Figure 2[ 13 ]) and twelve updated mechanisms are detailed below for the LHPA system as this system is the most studied, providing the most data to synthesize into mechanisms (see Figure 1 ). Other biological stress systems will be reviewed and these mechanisms discussed only if there are published data available.

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Developmental Traumatology Model of the Biological Effects of Trauma

1. Permanent changes occur as a result of childhood trauma onset

Elevated central CRH and CRF occurs with the onset of trauma. While this CRF elevation persists into adulthood; initial elevations of ACTH and cortisol levels become attenuated with chronic exposure to elevated CRH (a.k.a. CRF). High CRH in turn causes adaptive down-regulation of pituitary CRH and neural CRF receptors after trauma onset. These ideas agree with McEwen's [ 26 ] theory of allostatic load, which hypothesizes that organisms adapt to re-regulate psychobiological responses to chronic stress to prevent physical harm to the organism. Increasing allostatic load over the lifespan, however, increases vulnerability to stress disorders in response to new stressors. Thus, this down-regulation of CRF receptors may be an adaptive mechanism that regulates pituitary hypertrophy (a finding seen in maltreated children with PTSD[ 59 ]); while a down-regulation of CRF receptors would make neurons less responsive to CRF induced neuronal damage and seizures [ 60 , 61 ]. It should be noted that the opposite of chronic stress (i.e. environmental enrichment) delays seizures and neuronal damage in seizure prone animals through a CRF mechanism [ 62 ]. In support of this idea, higher levels of cerebrospinal fluid (CSF) CRF are seen in juvenile primates raised under unpredictable and adverse early rearing conditions [ 63 ] which longitudinally persists into young adulthood[ 64 ]. CSF CRF levels are higher in adults with childhood trauma histories [ 20 ]. In combat-related PTSD, elevated levels of central CRH were found [ 65 , 66 ]; childhood trauma is also a risk factor for a diagnosis of PTSD after combat experiences [ 67 ]. Chronically elevated CRF causes generalized arousal, anxiety, aggression, hypervigiliance, and stimulation of the sympathetic nervous system (SNS), all core symptoms of the PTSD hyperarousal cluster [ 24 ]. It also causes inhibition of feeding and sexual behavior, core symptoms of major depression, another common outcome of traumatic experiences in childhood [ 68 ].

2. Childhood trauma re-regulates biological stress systems

The long-term consequence of early trauma experiences and elevated CRF resets the regulation of the LHPA axis so that ACTH and cortisol secretions are set at lower 24-hour levels during baseline and non-stressful conditions. Adult studies of victims of childhood trauma consistently show lower cortisol levels [ 47 , 69 ]. In a meta-analysis, one of the most robust findings was that the longer the time since the trauma, the lower the morning cortisol, daily cortical volume, ACTH and postdexamethasone cortisol levels [ 47 ]. Since the adult PTSD studies focus on past trauma, the latter hypothesis may best explain the main differences in the data in childhood PTSD studies, where higher baseline cortisol levels were reported in most pediatric studies [ 41 - 47 ]; while lower 24 hour cortisol levels were seen in adults maltreated in youth [ 69 ]. This attenuation hypothesis is supported by data from the only longitudinal psychobiological study published to date; where nonstress cortisol levels were assessed at six time points from childhood through young adulthood in sexually abused and non-abused girls. In this study, nonstress cortisol activity was initially significantly higher in sexually abused girls (post abuse disclosure) compared to non-abused girls; but cortisol activity was significantly attenuated starting in adolescence and significantly lower during young adult follow-up compared to non-abused females [ 70 ].

3. Priming also called sensitization occurs as a result of childhood trauma

Priming occurs as a reflection of chronic compensatory adaptation of the LHPA axis long after trauma exposure, and it may be more likely to occur after pubertal maturation. Thus, studies which show greater cortisol or ACTH response after childhood trauma exposure may be the result of “priming.” LHPA axis regulation is affected by other hormones that are stress mediated such as arginine vasopressin and the catecholamines, both of which act synergistically with CRH.[ 19 ] A ‘primed system’ will ‘hyper’-respond during acute stress or during the occurrence of traumatic reminders because of the interactive neuroendocrine and neurotransmitter effects activated by current life stressors on the dysregulated LHPA axis. Another term used to describe priming is sensitization, defined as enhanced neuroendocrine, autonomic and behavioral responsiveness to stress as well as LHPA axis dysregulation [ 20 , 71 ]. Thus, when a new emotional stressor or traumatic reminder is experienced, the LHPA axis response will be enhanced (higher ACTH and higher cortisol levels). This has been seen in findings of increased ACTH secretion in depressed, abused youth who were continuing to experience chronic adversity [ 50 ] as well as in depressed women with a history of abuse who reported more recent chronic mild stress than abused women without major depressive disorder, who had blunted ACTH responses to CRF [ 56 ]. In a study of post institutionalized children that examined the effect of interactions between children and their caregivers, basal cortisol levels increased in response to parental interactions only in children who had previously been exposed to severe neglect from institutional rearing [ 72 ]. In addition, a prolonged elevation in cortisol levels occurred only when the previously neglected children were interacting with their caregivers, as interactions with unfamiliar adults led to similar cortisol levels in previously neglected and non-neglected children. These results therefore illustrated that previously neglected children generalized caregiver interactions as traumatic reminders and stressful experiences and thus demonstrated a disruption in the regulatory processes of the LHPA axis in response to these social interactions. Moreover, in adults with a history of child abuse, higher cortisol levels occur after exposure to traumatic reminders compared to neutral memories [ 73 ]. These results are the effects of ‘priming’ or sensitization.

4. Trauma timing and duration influence biological stress systems

Timing of trauma such as duration (single episode or chronic), age of trauma onset and stage of development influence cortisol levels post trauma. Cross-sectional studies show that trauma in infant primates [ 74 ] and very young or prepubertal children living in orphanages show low morning and daytime cortisol production [ 75 ], suggesting that prepubertal children may be more sensitive to negative feedback control mechanisms for cortisol output than older school-age children who show higher cortisol levels [ 41 - 47 ]. Sexually abused prepubertal children with major depression exhibited significantly lower mean baseline ACTH concentrations over the first 4 hours after sleep onset compared with control children[ 76 ]. Results of these cross-sectional studies suggest tight down-regulation of ACTH and cortisol due to elevated central CRF in very young children. Pituitary volumes increased with age [ 59 ] along with increasing cortisol levels, which are also associated with increasing body fat [ 77 ]. Significantly larger pituitary volumes are seen in pubertal and postpubertal maltreated children and adolescents with PTSD compared with non-maltreated controls [ 59 ]. Thus, elevated central CRH levels may lead to pituitary hypertrophy in traumatized children, which may be most pronounced during very early childhood and puberty, due to trophic factors. An adaptive response to elevated CRH levels, particularly during the sensitive periods of very early childhood and adolescence to elevated CRH levels, must be down-regulation of CRH receptors, or the resultant high cortisol levels would result in medical illness and brain structure damage. Tight control of cortisol secretion in infancy and attenuation of cortisol secretion after trauma onset and in response to increasing levels of cortisol that occur with increasing age and puberty are in accord with the theory of allostatic load [ 26 ], which hypothesizes that organisms adapt to chronic stress to prevent physical harm.

5. Individual differences in response to childhood trauma are associated with different types of biological stress system regulation

Individual differences in behavioral and emotional responses are associated with different types of LHPA axis dysregulation. Most studies show LHPA axis dysregulation consistent with elevated central CRF in youth who experience childhood trauma and depressive and anxiety symptoms [ 39 , 41 - 47 , 50 , 78 - 80 ] or co-morbid internalizing and internalizing behaviors [ 42 , 79 ]; while traumatized children with marked disruptive behavioral disorders or anti-social behaviors show lower cortisol levels [ 81 ].In addition, in a study of adults with moderate to severe child maltreatment histories and no diagnosable psychopathology, lower concentrations of cortisol and ACTH were seen in response to the Trier Social Stress Test compared to healthy adults without maltreatment histories [ 82 ], further suggesting that elevated central CRF is likely seen as a result of maltreatment even in resilient outcomes.

6. Early trauma type and trauma severity influence biological stress systems

Certain trauma types and increased overall trauma severity are more likely to result in LHPA dysregulation. For example, children who suffered from physical and sexual abuse occurring in the first 5 years of life were more likely to experience internalizing symptoms and LHPA axis dysregulation than those who suffered from abuse occurring after age 5, or from neglect, or emotional abuse [ 40 ]. Increasing severity of childhood trauma is associated with dysregulation of the LHPA axis. Children who experienced multiple maltreatment or those who experienced severe sexual abuse were more likely to have elevated cortisol levels [ 44 ]. Furthermore, in maltreated children with PTSD, 24 hour urinary cortisol concentrations correlated positively with increased trauma duration, and with PTSD intrusive and hyperarousal symptoms [ 42 ].

7. Genetic factors influence biological stress system responses to childhood trauma

LHPA-related genetic factors influence the effect of childhood trauma on the LHPA axis and its associated outcomes. Gene × environment interplay is important for the expression of both negative and resilience outcomes following childhood trauma. Gene x environment investigations are a relatively new area of study, so these data should be considered preliminary since this part of the field is still in its infancy.

Polymorphisms are normal variations in genes, which code for important proteins that build the body and its functions. Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation. Specific polymorphisms that are needed to form LHPA axis related structures (CRH and glucocorticoid receptors) appear to moderate the effect of child abuse on the risk for childhood neuroticism and adult depressive symptoms. The brain's CRH type 1 receptors (CRHR1) are located throughout the brain [ 27 ] and, when activated, produce symptoms of anxiety and depression [ 24 , 83 ].

There are few studies of gene × environment interplay in children. In one study, physically abused, emotionally abused, and neglected children who carried two copies of the TAT haplotype of the CRHR1 had significantly higher levels of neuroticism, a prelude to anxiety and depression, than non-maltreated children who had two copies of the TAT haplotype [ 84 ]. However, in this study, sexually abused children and children who had experienced 3 or 4 types of abuse, who had two copies of the TAT haplotype appeared to be protected from neuroticism compared to children who experienced other types of maltreatment [ 84 ]. In a follow-up study of these children, only maltreated children who carried two copies of the TAT haplotype exhibited a blunted slope of diurnal cortisol change, a sign of increasing allostatic load and dysregulation of the LHPA axis. However, the CRHR1 haplotype groups (zero or one copy vs. two copies) were not related to internalizing symptoms [ 85 ].

In contrast, one study of adult carriers of both the TCA (i.e., T-alleles, formed of SNP, rs7209436, and C allele formed by SNP rs4792887) and TAT haplotypes (i.e., A-allele formed of SNP rs110402) as well as the 2 SNPs (rs7209436 and rs242924) located in intron 1 of the CRHR1 gene, were significantly protected from having major depression despite histories of child abuse [ 86 ]. This finding was replicated in a relatively large study of women with child maltreatment [ 87 ], and in African American men and women [ 88 ], but not replicated in a study of European men and women, who experienced childhood maltreatment [ 87 ]. On the other hand, adults with moderate to severe child maltreatment histories and the GG polymorphisms of the CRHR1 gene (rs110402) showed a significant interaction with maltreatment for increased cortisol responses to dexamethasone/corticotropin-releasing hormone pharmacological challenge compared to those adults with maltreatment and the A allele [ 88 ]. Higher cortisol is a well-replicated finding in adults with major depression [ 19 , 89 ]. Furthermore, sex effects may be important in gene × environment interplay. In another study of adults with child abuse histories, the protective effect of the CRHR1 polymorphisms (rs110402 A-allele) against developing adult depression and with decreased cortisol response in the dexamethasone/ corticotropin-releasing hormone pharmacological challenge were observed only in men, and not in women [ 90 ] , a finding opposite to the one described above [ 87 ].

Gene × environment interplay was seen in a prospective study of the FKBP5 gene, a gene that inhibits glucocorticoid-receptor-mediated glucocorticoid activity [ 91 ]. In this study, 884 Caucasians with no history of depression were enrolled at age 12 to 14 years, and followed for 10 years [ 92 ]. Those who were homozygous for the minor alleles and had traumatic (but not separation (i.e., lost of parent through death or divorce) events (particularly severe child maltreatment) prior to age 24 years, showed an increased incidence of depression on follow-up, suggesting that the minor allele of the FKBP5 polymorphism and childhood trauma interacted to predict adult depression. Three variants in the FKBP5 gene (rs4713916, rs1360780, and rs3800373) were associated with a failure of cortisol responses to return to baseline in healthy adults after psychosocial stress, suggesting a genotype-dependent risk of chronically elevated plasma cortisol levels in the context of acute stress as a possible mechanism for the increased risk of stress related mental disorders, such as depression and PTSD in adults with these alleles [ 93 ]. Cross-sectional studies have also found interaction for adults who carry the minor FKBP5 allele and have child maltreatment histories as they have increased rates of depression [ 94 ], PTSD [ 95 , 96 ], and suicide risk [ 97 ]. Interestingly, in one cross sectional study, the less common FKBP5 haplotype (H2) was associated with an increased risk of overt aggressive behavior in adult male prisoners who have a history of physical abuse[ 98 ]. In an imaging study, healthy young adults, were genotyped for 6 FKBP5 polymorphisms (rs7748266, rs1360780, rs9296158, rs3800373, rs9470080 and rs9394309) previously associated with psychopathology and/or LHPA axis function [ 99 ]. Interactions between each SNP and increased levels of emotional neglect, were associated with heightened reactivity to angry and fear faces in the dorsal amygdala which suggests a neurobiological mechanism linking PTSS and depressives symptoms of hyperarousal and hypervigilience to negative affect and to psychopathology [ 99 ]. Hence, investigations of gene × environment interplay suggest that risk genes may interact with childhood trauma to produce different adult emotional, behavioral, and neurobiological outcomes.

8. Epigenetic factors influence biological stress system responses to childhood trauma

LHPA-related epigenetic factors influence the effect of childhood trauma on the LHPA axis and its associated negative behavioral and emotional outcomes. Epigenetics is also a relatively new area of study, so the limited data to date will be described here. The epigenome consists of chromatin, the protein-based structure around DNA, and a covalent modification of the DNA itself by the methylation of cytosine rings found at CG dinucleotides [ 100 ]. The epigenome determines the accessibility of the DNA to convert genetic information into the messenger RNA necessary for gene function. Early traumatic experiences are associated with hyper- and demethylation of specific regulatory sites in key biological stress system genes including the gene encoding of the glucocorticoid receptor [ 101 ] and the neuropeptide arginine vasopressin (AVP) which is co-localized with CRH and released with CRH from the paraventricular nucleus of the hypothalamus during stress [ 102 ]. Increased methylation of key biological stress system genes can silence a gene's activity by making the gene inaccessible for transcription, while demethylation may make a gene accessible for transcription. Thus, childhood trauma can have a long-term impact on gene activity without changing an individual's DNA sequence (i.e., genes)[ 103 , 104 ]. Epigenetic effects may account for the inconsistent main gene and gene x environment results in the studies previously reported.

Animal studies have provided the first evidence of epigenetic effects caused by early trauma. Rats developing in optimal environments show less stress reactivity [ 105 ]. Because lactating female Long-Evans rats exhibit individual variation in the frequency of pup licking/grooming, high or low levels of pup licking/grooming are considered a maternal phenotype [ 106 ]. As adults, the offspring of high licking/grooming mothers show less plasma ACTH and cortisol responses to acute stress in comparison with animals reared by low licking/grooming mothers [ 106 , 107 ]. The offspring of high licking/grooming mothers also show significantly increased hippocampal glucocorticoid receptor mRNA and protein expression, enhanced glucocorticoid negative feedback sensitivity, and decreased hypothalamic CRF mRNA levels, which all indicate decreased stress reactivity as a result of optimal quality of care.[ 105 ] Furthermore, DNA methylation patterns differ in high licking/grooming versus low licking/grooming offspring. The glucocorticoid receptor promoter sequence in the hippocampus of adult offspring of low licking/grooming mothers is hypermethylated and functionally less sensitive to cortisol feedback. Maternal behaviors also affect other biological systems that are associated with the LHPA axis. Prolonged periods of maternal separation alter the methylation state of the promoter for the arginine vasopressin gene (AVP) in the pup, increasing hypothalamic vasopressin AVP synthesis and LHPA responses to stress, along with memory deficits and learned helplessness behaviors [ 108 ].

In a rodent model of infant maltreatment, abuse and neglect during infancy decreases brain-derived neurotropic factor (BDNF) gene expression in the adult prefrontal cortex (PFC) [ 109 ]. In addition, these investigators found that chronic treatment with a DNA methylation inhibitor lowered levels of methylation in male and female rats exposed to early maltreatment. They also showed not only that infant trauma was associated with poor mothering in the next generation and that these epigenetic changes in DNA methylation were passed on from one generation to the next generation, even if the offspring of an abusive dam (mother rat) was cross-fostered with a non-maltreating dam, thereby indicating heritability of these epigenetic changes [ 109 ].

Increased methylation in a neuron-specific glucocorticoid receptor (NR3C1) promoter was seen in human postmortem hippocampus obtained from suicide victims with a history of childhood abuse compared to suicide victims without child abuse histories and controls who died of non-suicide related causes, demonstrating an association between early trauma and epigenetic alterations [ 101 ]. Decreased hippocampal glucocorticoid receptor expression due to epigenetic changes likely increased LHPA activity and enhanced the risk of both depression and suicide in adults who were child abuse victims [ 101 ]. These findings link the previously described data from rats to humans and suggest a common effect of quality of parental care on the epigenetic regulation of hippocampal glucocorticoid receptor expression that can lead to health or the LPHA axis dysregulation seen in childhood PTSD and PTSS and adult depression.

In addition, a preliminary investigation showed that experiencing foster care during childhood is associated with changes in methylation of genes related to both the HPA axis and the immune system [ 110 ]. This study therefore supports the idea that childhood trauma may be linked to changes in genetic expression and resulting mental and medical health problems.

9. Gender differences influence the effects of childhood trauma on biological stress systems

Gender differences influence the effect of childhood trauma on the HPA axis. Research involving men and women who were exposed to early trauma but who did not have any psychopathological diagnoses has shown stronger associations between trauma and increased CRF levels in men than in women [ 111 ]. In children, girls with histories of physical abuse had higher levels of urinary oxytocin, a neuroendocrine peptide that down-regulates cortisol and is associated with complex social behaviors, and lower levels of salivary cortisol following an experimental stressor when compared to non-abused girls; while abused and non-abused boys did not differ in their hormonal responses [ 112 ]. Early trauma and gender differences are an area of research that warrants further investigations, as a prospective investigation showed that maltreated males may be more likely to be arrested for violent offenses as adults [ 113 ], thus becoming prisoners and less likely to be involved in retrospective research studies. This fact can lead to a selection bias in retrospective studies, and a possibly mistaken idea that females are more vulnerable to early trauma. Early trauma experiences may lead to greater down-regulation of cortisol due to high levels of CRF and other stress markers, in males compared to females, findings that are commonly seen in individuals with antisocial behaviors [ 81 ].

10. Social support buffers biological stress system dysregulation and its associated negative behavioral and emotional outcomes

As adults, the offspring of high licking/grooming mothers show decreased stress and cortisol reactivity as a result of optimal quality of care [ 105 ]. In preschool children, quality of childcare is associated with a buffering of hypothalamic-pituitary-adrenal axis to stress [ 114 ]. In adult studies, social support was associated with a decrease in the cortisol response to the Trier Social Stress Test in men [ 115 ]. Furthermore, decreased cortisol response and activity in the dorsal anterior cingulate, a brain region involved in distress separation, were seen in response to an exclusion neuroimaging task when daily social support was part of the research paradigm [ 116 ]. Further research is needed on the impact of social support in traumatized children.

11. Individual biological stress systems dysregulation in response to childhood trauma and the genes associated with the function of these systems influence other biological systems during development to contribute to psychopathology

For example, the LHPA modulates the locus coeruleus-norepinephrine/SNS system and the immune system [ 19 ]. When the hypothalamus releases CRH in response to stress, the locus coeruleus becomes activated indirectly through the central amygdala [ 19 ]. Serotonin modulates LHPA activity [ 117 ]. Furthermore, having more than one type of a depression risk allele in two different biological stress systems (i.e., the risk CRHR1 polymorphisms in the LHPA axis and the short allele of serotonin transporter gene promoter polymorphism (5-HTTLPR) in the serotonin system) is associated with current depressive symptoms in adults with less severe levels of child abuse and neglect as measured on the Childhood Trauma Questionnaire [ 118 ].

12. Biological stress systems dysregulation in response to childhood trauma adversely influences cellular, cognitive and brain development [ 42 , 119 , 120 ]

Human brain maturation is marked by the acquisition of progressive skills in physical, behavioral, cognitive, and emotional domains. Myelin, a fatty white substance produced by glial cells, is a vital component of the brain. Myelin encases the axons of neurons, forming an insulator, the myelin sheath and is responsible for the color of white matter. Myelination of newly formed neuronal networks increases neural connectivity and parallels these developmental changes. Brain development occurs with an overproduction of neurons in utero, increases in neuron size, synapses, and neural connections during childhood and adolescence, selective elimination of some neurons (apoptosis) with corresponding decreases in some connections and strengthening of others and corresponding increases in myelination to hasten these connections. Synapses, dendrites, cell bodies, and unmyelinated axons, which form the brain's gray matter, decrease during development [ 121 ]. Glucocorticoids are important for normal brain maturation including initiation of terminal maturation, remodeling axons and dendrites and affecting cell survival [ 26 , 122 ]. Both suppressed and elevated glucocorticoid levels can impair brain development and function [ 26 , 122 ]. During brain maturation, stress and elevated levels of stress hormones and neurotransmitters may lead to adverse brain development through apoptosis [ 123 - 125 ], delays in myelination[ 126 ], abnormalities in developmentally appropriate pruning [ 127 , 128 ], the inhibition of neurogenesis[ 129 - 131 ], or stress induced decreases in brain growth factors[ 132 ]. Indeed, maternal deprivation increases the death of infant rat brain cells [ 133 ]. Consequently, dysregulation of a maltreated child's major stress systems likely contributes to adverse brain development and leads to psychopathology [ 13 ].

Telomeres are the repetitive TTAGGG sequence at the end of linear chromosomes and with each division, telomeres get shorter, and are considered a molecular clock for cellular aging [ 134 ]. In a cross sectional study of children who were previously institutionized, telomere length was shorter than children without such histories[ 135 ]. In a prospective longitudinal study of children, from ages 5 to 10 years, children who experienced two or more types of violence (measured as bullying, witnessing domestic violence, and physical abuse), have increased telomere erosion, a marker of premature cellular aging, compared to children who did not experience violence [ 120 ]. This landmark study suggests that children, who experience trauma, have decreased telomere maintenance, a potential mechanism (“premature aging”) for adverse brain development, mental health problems, and chronic health problems in adults with a childhood history of trauma [ 13 , 136 ].

The Locus Coeruleus-Norepinephrine/Sympathetic Nervous System (SNS)/Catecholamine System and Childhood Trauma

When the hypothalamus releases CRH in response to a stressor, the locus coeruleus (LC)-norepinephrine/SNS system becomes activated indirectly through the central amygdala. Activation of the locus coeruleus causes an increase in the release of norepinephrine throughout the brain and results in symptoms of PTSD and anxiety [ 13 ]. The locus coeruleus is an ancient brain structure that increases activation of the sympathetic nervous system (SNS), a part of the autonomic nervous system that controls the “fight or flight or freeze” response [ 13 ]. The catecholamines (epinephrine, dopamine, and norepinephrine) and corresponding increased activity in the SNS work to generally prepare an individual for action by redistributing blood away from the skin, intestines, and kidneys and to the brain, heart and skeletal muscles [ 137 ], and by diverting energy through a central dopamine mechanism that inhibits the prefrontal cortex, from a thinking and planning mode to a survival and alertness mode [ 138 , 139 ].

Sexually abused girls with dysthymia demonstrated greater 24-hour levels of total urinary catecholamines than non-abused girls [ 140 ]. Maltreated boys and girls with PTSD showed greater levels of urinary catecholamines at baseline than non-maltreated healthy children and non-maltreated children with generalized anxiety disorder [ 42 ]. Urinary catecholamines positively correlated with duration of PTSD trauma and number of PTSD internalizing and child dissociative symptoms [ 42 ]. In a study of children who experienced motor vehicle accidents, significantly elevated plasma noradrenaline concentrations were seen prospectively, at both months 1 and 6, after the accident, compared to the non-PTSD and control groups, further suggesting that higher catecholamines occur as a result of trauma and PTSD [ 141 ]. In a study of police academy recruits, those with early trauma exposure demonstrated heightened 3-methoxy-4-hydroxy-phenylglycol (MHPG) (the major metabolite of norepinephrine) response after watching critical incident videos [ 142 ]. An adult positron emission tomography imaging study demonstrated significantly reduced norepinephrine transporter (NET) availability in the locus coeruleus in PTSD which would lead to chronic stimulation of the locus coeruleus as a result of increased levels of norepinephrine. This finding positively correlated with PTSD hypervigilance symptoms. Furthermore, in a gene x environment analysis, adult carriers of the Val allele of the Catechol-O-methyltransferase (COMT) polymorphism (a gene involved in dopamine degradation) with a history of sexual abuse showed a higher disposition toward anger, symptoms commonly seen in PTSD patients, compared with adults homozygous for the Met allele. The Val allele is associated with increased dopamine neurotransmission in the prefrontal cortex, which is associated with deficits in executive function [ 138 , 139 ] and increased risk for impulsive anger. On the other hand, adults with early trauma and the Val/Val genotype showed increasing levels of dissociation corresponding to increased exposure to higher levels of childhood trauma [ 143 ]. Dissociation is a failure to integrate sense of self with current and past memories and emotions and is a pathological defense to ward off anxiety that is also associated with non-intentional antisocial behaviors. Dissociation is a different construct from depression and anxiety. Thus studies in both children and adults have consistently demonstrated higher locus coeruleus (LC)-norepinephrine/SNS system activity associated with childhood trauma and PTSD, while down-regulation of this system due to trauma may be associated with antisocial behavior and dissociation.

The Serotonin System and Childhood Trauma

Serotonin is a critical element of the stress response system [ 13 ]. Serotonergic neurons project diffusely from the central serotonin raphe nuclei in midbrain to important cortical and subcortical brain regions (e.g., prefrontal cortex, amygdala, hippocampus) that play known roles in regulating emotions (e.g., mood), behaviors (e.g., aggression, impulsivity)[ 144 , 145 ], cognitive function, motor function, appetite, and the regulation of many physiological processes (e.g. cardiovascular, circadian, neuroendocrine respiratory, and sleep functions [ 144 , 146 ]). Serotonin is an important regulator of morphogenetic activities during early brain development, influencing cell proliferation, migration, and differentiation, thus influencing child brain development [ 147 ]. In preclinical animal studies, decreased levels of serotonin activity are associated with increased levels of aggressive behaviors in rodents and primates exposed to early adversity [ 148 ]. Mice genetically engineered to lack the serotonin transport gene show increased LHPA axis activation to stress, suggesting that serotonin modulates LHPA activity [ 117 ]. Disruptions in serotonin's regulatory functioning are linked with several psychopathological disorders that are commonly seen in children and adults with childhood trauma. For example, decreased levels of serotonin activity have been associated with mental health problems such as depression and anxiety [ 149 ] as well as with aggressive behaviors in individuals with personality disorders such as borderline personality disorder[ 150 ].

Early trauma dysregulates serotonin in humans. The serotonin transporter protein is involved in the reuptake of serotonin from the synapse, and is critical to serotonin regulation in the brain. The short allele of the serotonin transporter gene promoter polymorphism (5-HTTLPR) interacts with maltreatment in the development of childhood depression. The short allele is associated with reduced transcriptional activity of serotonin, so that there is less central serotonin available in the brain; while the long allele has at least twice the basal level of transcriptional activity of the short variant [ 151 ]. Most studies regarding the effects of 5-HTTLPR are in adults maltreated as children. A large epidemiological study demonstrated that there were no main genetic effects, but carriers of the S-allele had a higher risk of developing depressive and suicidal symptoms when exposed to stressful life events and childhood maltreatment [ 152 ]. Children who were homozygous for the short allele of 5-HTTPR demonstrated a significantly elevated vulnerability to depression, but only in the presence of maltreatment; but the presence of positive supports reduced this risk [ 153 ]. Having two short-short alleles of the 5-HTTLPR gene moderated the association between bully victimization and emotional problems, such that frequently bullied children were at an increased risk as adolescents for depression or anxiety; the short-long and long-long genotypes did not confer an increased risk [ 154 ]. However other studies have not shown an increased vulnerability to depression as a function of interactions between the short allele and maltreatment. Instead, they have shown increased risk with the long-long allele [ 85 , 155 ]. One study of 595 youth suggests that genetic variation has a negligible effect on promoting resilience among maltreated children [ 156 ]. In other words, non-maltreated children with the short-short genotype were more likely to have higher resilient functioning; while maltreated children with the short-short genotype were more likely to have lower resilience [ 156 ]. This study agrees with controversial meta-analyses that have found that adverse childhood events had a main effect on depressive outcomes regardless of 5-HTTLPR polymorphisms [ 157 , 158 ]. The discrepant findings in adults may be caused by failure to include trauma versus a stressful life event, trauma age of onset, trauma duration, and trauma type in the gene x environment interaction analyses, as this interaction showing that adults with histories of child maltreatment were found in another meta-analysis to be at increased risk for depression [ 159 ]. On the other hand, in a forensic sample of 237 men with elevated levels of child abuse and neglect given the Childhood Trauma Questionnaire, measures of psychopathy were highest among carriers of the 5-HTTPR long allele and carriers of the low activity monoamine oxidase A (MAOA) gene [ 160 ]. Thus resilience is a complex issue, as psychopathy as an outcome may be more harmful to society than depressive symptoms.

Genes associated with the serotonin system have been linked to other adverse outcomes in the presence of childhood trauma. The MAOA gene codes for an enzyme that selectively degrades the biogenic amines dopamine, serotonin, and norepinephrine after reuptake from the synaptic cleft, and influences behavioral regulation [ 161 ]. Meta-analyses revealed that the association between early family adversity (particularly between neglect or physical abuse), and the short version of the MAOA gene, was significantly associated with a general index of mental health problems, antisocial behavior, attentional problems, and hyperactivity in boys [ 162 ]. Adolescent boys with the short MAOA allele who were exposed to maltreatment or poor-quality family relations had more alcohol-related problems than maltreated boys with the longer MAOA allele [ 163 ]. Early use of alcohol in youth was predicted by an interaction of the short alleles of 5-HTTLPR and maltreatment [ 164 ]. Further, women with a history of sexual abuse and the short MAOA allele were more likely to demonstrate alcoholism and antisocial personality disorder than were women with a history of sexual abuse and the long allele [ 165 ].

Furthermore, genetic polymorphisms can have additive genetic effects. Children who were homozygous for the short allele of 5-HTTLPR, and had the val66met variant of the brain-derived neurotropic factor (BDNF) gene, and had been maltreated, were at increased risk of depression.

In summary, the serotonin system and the genes regulating the serotonin system are influenced by early trauma. However, the field has not yet advanced to the point where treatment can be tailored to an individual child. More work needs to be done on gene-gene interactions, possible epigenetic effects, trauma variables, and other factors such as social supports, to achieve this aim.

The Oxytocin System and Childhood Trauma

Oxytocin plays an important role in interpersonal relationships. Involved in the regulation of an individual's sexual response and milk production, this hormone is also responsible for the regulation of a wider range of social interactions, including social memory and cognition, emotion recognition, empathy, and attachment [ 166 ]. In addition, the oxytocin system is involved in the regulation of the body's response to stress. Research in rats demonstrated a relationship between oxytocin and the mother's relationship with her offspring, as those mothers who engaged in more licking/grooming behaviors exhibited higher levels of oxytocin receptor binding in the amygdala [ 167 ]. Similarly, rat mothers who demonstrated high levels of licking/grooming had increased levels of oxytocin gene expression and a subsequent increase in dopamine reward production. Mothers who demonstrated lower levels of licking/grooming behaviors, had lower levels of oxytocin gene expression, thereby highlighting the important role that oxytocin plays in the attachment bond [ 168 ].

Research involving humans has similarly demonstrated that negative life events can disrupt the body's regulation of oxytocin. Decreased levels of oxytocin have been found in women exposed to early maltreatment—a relationship that was shown to be especially strong when the form of maltreatment was emotional abuse [ 20 ]. Gender differences have also been found in the relationship between childhood trauma and oxytocin regulation. Focusing on oxytocin response to an experimental stressor in abused girls and abused boys, girls exposed to physical abuse exhibited higher levels of oxytocin, as well as decreased levels of cortisol, in response to the experimental stress; while there was no difference in hormone response to the stress in the abused boys [ 112 ]. In the Adverse Childhood Experiences Study, a relationship was found between exposure to early trauma and increased promiscuity[ 136 ]. To explain this relationship, the researchers pointed out that disruptions in oxytocin regulation of social attachments during childhood can lead to high oxytocin and thus problems forming fast and less discriminate personal attachments during adulthood [ 136 ].

On the other hand, a strong moderating effect of a positive social environment has also been found in adults with a specific allele of the oxytocin receptor gene OXTR who had been exposed to early stress, as increased resilience in adulthood was found only in those individuals who had been surrounded by a positive family environment during childhood [ 169 ]. Further research is needed on the impact of oxytocin on emotional and behavioral outcomes in traumatized children.

The Immune System and Childhood Trauma

Activation of the immune system involves the production of cytokines, which promote an inflammatory reaction to infection or pathogens in the body. Although one of the main effects of this reaction is to produce the physical symptoms of sickness (e.g., fever, nausea, and fatigue), activation of cytokines that promote inflammation are implicated in depression, a common outcome of early trauma [ 170 ]. A recent systematic review provided evidence that supports the relationship between pro-inflammatory cytokines and increased levels of depression and anxiety in adolescents [ 171 ]. Higher levels of plasma antinuclear antibody titers have been found in girls who have been sexually abused, suggesting that exposure to this form of stress may inhibit the body's means of suppressing the B lymphocytes, or the lymphocytes that produce antibodies, thereby leading to the increased levels of the antibody titers found in the abused girls [ 172 ]. Increased levels of inflammatory cytokines, as well as decreased levels of anti-inflammatory cytokines, have been associated with adult PTSD and exposure to chronic stress [ 173 , 174 ]. In women who had experienced early maltreatment, those who had been diagnosed with PTSD had higher activation levels of T cells than those who did not have PTSD More specifically, investigators found a positive correlation between T-cell activation levels and intrusive symptoms of PTSD [ 175 ]. Similar results were found in a study of women with PTSD secondary to physical or sexual abuse during childhood, where these women demonstrated increased inflammatory and immune activity[ 176 ]. Other investigators demonstrated that greater concentrations of interleukin-6 (IL-6), a proinflammatory cytokine, concentrations were seen during the Trier Social Stress Test in adults with child maltreatment histories compared to adults without such histories [ 177 ]. Furthermore in a longitudinal study of a New Zealand birth cohort (n=1037), it was demonstrated that adults with histories of poverty, social isolation or maltreatment had elevated rates of depression and age-related metabolic disease risks in adulthood including higher body mass index, total cholesterol, glycalated hemoglobin, and low levels of high-density lipoprotein, low maximum oxygen consumption, and higher levels of C-reactive protein, a measure of inflammation [ 178 ]. Further children exposed to a greater number of these adverse childhood risk factors had greater age-related disease risk in adult life [ 178 ]. The increased activation of cytokines and dysregulation of the immune system, along with the other biological stress response systems, such as the HPA axis and the LC/SNS systems, that occurs in response to early adversity, can lead to hypertension, accelerated atherosclerosis, metabolic syndrome, impaired growth, and immune system suppression and poorer medical health in adults with child trauma histories [ 179 ].

The Effect of Childhood Trauma on Neuropsychological Functioning and Cognitive Development

Cross-sectional studies examining maltreatment trauma in childhood have shown lower IQs and deficits in language and academic achievement in maltreated children compared to children who have not been exposed to maltreatment [ 180 - 185 ]. The link between early trauma and IQ has been demonstrated through a twin study, where after controlling for the effect of shared heritability, domestic violence was associated with lower IQ (e.g., mean of 8 points) in exposed versus non-exposed children [ 186 ]. Exposure to trauma in childhood has also been associated with executive deficits [ 187 - 189 ].

Fewer studies have examined the effect of child maltreatment on a broader, more comprehensive range of neuropsychological functioning. A study comparing previously institutionalized children exposed to long periods of neglect with those exposed to brief periods of institutionalization as well as children raised in their biological families found that the children who experienced prolonged neglect performed more poorly in the domains of visual attention, memory, learning and inhibitory control, but that these previously institutionalized children did not demonstrate deficits when the tasks involved auditory or executive processing [ 190 ]. These results therefore highlight that specific domains of cognitive functioning may be more sensitive to early neglect than others. Lower performance in IQ, complex visual attention, visual memory, language, verbal memory and learning, planning, problem solving, speeded naming and reading and mathematics achievement were seen in neglected children with and without PTSD compared to socioeconomically similar controls [ 191 ]. Furthermore, PTSD symptom number, and the failure to supervise, witnessing violence, and emotional abuse variables were each associated with lower scores in IQ, academic achievement, and neurocognitive domains [ 191 ]. However, neglected children with PTSD due to witnessing interpersonal violence had lower performance levels on the NEPSY Memory for Faces-Delayed than both neglected children who witnessed domestic violence and did not have PTSD and children not exposed to maltreatment or violence indicting that PTSD was associated with impaired consultation of memory [ 191 ]. Childhood PTSD subsequent to witnessing interpersonal violence has also been associated with lower levels of performance on the California Verbal Learning Test-Children's Version when compared to those without PTSD, while both PTSD and non-PTSD groups of youth exposed to domestic violence demonstrated deficits in executive functioning, attention, and IQ standardized scores[ 192 ].

In a study comparing the performance of abused youth with PTSD, abused youth without PTSD, and non-maltreated youth on comprehensive neuropsychological testing, both groups of maltreated youth performed worse than the control youth, with deficits in IQ, academic achievement, and all neurocognitive domains expect for fine-motor functioning[ 193 ]. The maltreated youth with PTSD showed greater deficits in visuospatial abilities than the maltreated youth without PTSD, and sexual abuse was found to be negatively associated with language and memory scores. A negative relationship was found between the number of maltreatment types experienced and academic achievement, demonstrating that cumulative trauma leads to neuropsychological problems that are unrelated to PTSD symptoms[ 193 ]. Data from the National Survey of Child and Adolescent Well-Being (NSCAW) study demonstrated that maltreated children who experienced maltreatment during multiple developmental periods had more externalizing and internalizing problems and lower IQ scores than children maltreated in only one developmental period suggesting that trauma duration has negative and cumulative cognitive effects [ 194 ].

Longitudinal prospective studies involving adolescents and adults exposed to maltreatment in childhood agree with the cross-sectional studies and have demonstrated lower IQ scores and deficits in reading ability [ 195 - 200 ]. The research on the effects of early trauma on cognitive function indicates that early trauma is associated with adverse cognitive development and that this is likely reflected in adverse brain development.

The Effect of Childhood Trauma on Brain Development

An early, unexpected, trauma, maternal deprivation, increases the death of both neurons and glia cells in cerebral and cerebellar cortexes in infant rats [ 133 ]. Increased exposure to cumulative life stress (e.g., exposure to severe marital conflict, severe chronic illness of a close family member or friend) was associated with poorer spatial working memory performance and decreased volumes of white and gray matter in the prefrontal cortex of non-maltreated youth [ 201 ]. Pediatric imaging studies demonstrated that both cerebral and cerebellar volumes are smaller in abused and neglected youth compared to non-maltreated youth [ 202 - 206 ]. In one research study, maltreated subjects with PTSD had 7.0 % smaller intracranial and 8.0% smaller cerebral volumes than non-maltreated children [ 119 ]. The total midsagital area of corpus callosum, the major interconnection between the two hemispheres that facilitates intercortical communication, was smaller in maltreated children [ 119 ]. Smaller cerebral volumes were significantly associated with earlier onset of PTSD trauma and negatively associated with duration of abuse [ 119 ]. PTSD symptoms of intrusive thoughts, avoidance, hyperarousal and dissociation correlated negatively with intracranial volume and total corpus callosum measures [ 119 ]. another study showed smaller brain and cerebral volumes and attenuation of frontal lobe asymmetry in children with maltreatment-related PTSD or subthreshold PTSD compared with archival non-maltreated controls [ 203 ].

However, these two previously described studies did not control for low socioeconomic status, which influences brain maturation through ecological variables [ 119 , 207 ]. In another study which controlled for socioeconomic status, children with maltreatment-related PTSD had smaller intracranial, cerebral and prefrontal cortex, prefrontal cortical white matter, and right temporal lobe volumes and areas of the corpus callosum and its subregions and larger frontal lobe CSF volumes than controls [ 205 ]. The total midsagittal area of corpus callosum and middle and posterior regions remained smaller; while right, left, and total lateral ventricles and frontal lobe CSF were proportionally larger than controls, after adjustment for cerebral volume [ 205 ]. Brain volumes also positively correlated with age of onset of PTSD trauma and negatively correlated with duration of abuse [ 205 ]. The larger lateral ventricles were only seen in maltreated males, suggesting that males are more vulnerable to the neurotoxic effects of childhood maltreatment. Smaller cerebellar volumes were seen in male and female maltreated children with PTSD [ 204 ]. Younger age of onset and longer trauma duration were significantly correlated with smaller cerebellum volumes [ 204 ]. Smaller cerebellum volumes were also seen in previously institutionized youth [ 202 ]. The cerebellum is a complex posterior brain structure that is involved in cognitive functions [ 208 ], decision making, reward circuits [ 209 , 210 ] and the default mode network that is associated with understanding social intentions [ 211 ]. Child maltreatment is also associated with adverse effects in individual brain structures that are involved in reward and default network processing. In a large study of 61 medically healthy youth (31 males and 30 females) with chronic PTSD secondary to abuse, who had similar trauma and mental health histories, and 122 healthy non-maltreated controls (62 males and 60 females), the midsagital area of the corpus callosum subregion 7 (splenium) was smaller in both boys and girls with maltreatment-related PTSD compared to their gender-matched comparison subjects [ 212 ]. Youth with PTSD did not show the normal age-related increases in the area of the total corpus callosum and its region 7 (splenium) compared to non-maltreated children [ 212 ]. This was an important finding for several reasons. The maltreated and control children were not prenatally exposed to substances and had no pregnancy or birth trauma, were psychotropically naïve, and had no history of substance abuse or dependence, thus excluding confounds which are commonly seen in maltreated children [ 213 , 214 ] and not addressed in exclusion criteria in most neurobiological studies published to date. The axons in the splenium of the corpus callosum myelinate during adolescence and are important to the posterior reward circuits and the posterior default networks [ 215 ]. Additionally, clinical symptoms of PTSD intrusive, avoidant, and hyperarousal symptoms, symptoms of childhood dissociation, and child behavioral checklist internalizing T score significantly and negatively correlated with corpus callosum measures [ 212 ]. Children with maltreatment-related PTSD had reduced fractional anisotropy values on diffusion tensor imaging brain scans of white matter, indicating less myelin integrity in the medial and posterior corpus, a region which contains interhemispheric projections from brain structures involved in circuits that mediate emotional and memory processing, core disturbances associated with trauma history [ 216 ]. Smaller corpus callosum area measures were seen in another anatomical magnetic resonance imaging brain study of neglected children with psychiatric disorders compared to nonmaltreated children with psychiatric disorders, suggesting that smaller corpus callosum measures may be a consequence of maltreatment [ 217 ].

Furthermore, areas of executive function show evidence of adverse brain development in children with maltreatment-related PTSD. Decreased N-acetylaspartate (NAA) concentrations are associated with increased metabolism and loss of neurons [ 218 ]. For example, brain NAA levels decrease when someone has neuronal loss such as a stroke. A preliminary investigation suggested that maltreated children and adolescents with PTSD demonstrated lower NAA/creatine ratios in the medial prefrontal cortex compared to sociodemographically matched controls [ 219 ]. These findings suggest neuronal loss in the medial prefrontal cortex, an executive brain region, in pediatric maltreatment-related PTSD. Another group found that decreased left ventral and left inferior prefrontal gray matter volumes in maltreated children with PTSD symptoms negatively correlated with bedtime salivary cortisol levels, further suggesting that early trauma damages executive regions [ 220 ]. One functional imaging study of maltreated children and adolescents with PTSD symptoms showed significant decreases in inhibitory processes compared to nonmaltreated controls [ 221 ], and another showed impaired cognitive control in adopted children with histories of maltreatment who were formerly raised in foster care [ 222 ]. These investigations strongly suggest that childhood maltreatment interferes with executive or control circuits, whose dysregulation is an important contributor to adolescent and adult mental health and substance use disorders. Thus, childhood trauma can have detrimental effects on the brain networks that establish an individual's ability to think, and regulate their sense of self, motivations, and behaviors.

Another important contributor to memory and the default mode network is the hippocampus. Unlike findings in adult PTSD, where several studies reported hippocampal atrophy [ 223 ], maltreated children and adolescents with PTSD or subthreshold PTSD showed no anatomical differences in limbic (hippocampal or amygdala) structures cross-sectionally [ 119 , 203 , 205 ] or longitudinally [ 224 ]. However, investigators have demonstrated functional brain differences in the amygdala and hippocampus of maltreated youth compared to non-maltreated children [ 222 , 225 ]. One study suggests that hippocampal atrophy may be a latent developmental effect of childhood maltreatment [ 226 ].

Child maltreatment is also associated with adverse development of brain reward regions involved in recognizing emotions and social cognition such as the superior temporal gyrus [ 206 ] and the orbital frontal cortex [ 227 ]. In carefully screened young adult subjects, those with a history of verbal abuse and no other forms of maltreatment had reduced fractional anisotropy on diffusion tensor imaging brain scans of white matter in the arcuate fasciculus in left superior temporal gyrus, the cingulum bundle by the posterior tail of the left hippocampus, and the left body of the fornix, indicating decreased integrity in these language neural pathways[ 228 ]. Furthermore, fractional anisotropy values negatively correlated with verbal abuse experiences [ 228 ]. In healthy adult women, a history of sexual abuse was specifically associated with hippocampal, corpus callosum, or frontal cortex reductions if it occurred during specific developmental age periods, indicating vulnerable windows for the brain effects of child trauma [ 217 ].

Functional neuroimaging studies of adults with PTSD related to childhood maltreatment have shown decreased levels of executive and attentional function as reflected by decreased activation in the dorsal control networks with corresponding increased activation of the amygdala and hippocampus and other structures of the affective emotional networks during emotional challenge tasks; suggesting dorsal control network deficits in adult PTSD secondary to childhood trauma [ 229 - 231 ]. Research using functional neuroimaging of children and adolescents exposed to maltreatment has shown similar executive, attentional, and affective emotional dysregulation [ 221 , 222 , 232 - 234 ]. Further, previously institutionalized children demonstrated decreased prefrontal white matter microstructural organization on measures of diffusion tensor imaging that was associated with neurocognitive deficits in spatial planning and a visual learning and memory task compared to non-neglected controls [ 235 ].

In another study of healthy adult women with a history of childhood sexual abuse, investigators found higher T2 relaxation time (an indirect index of resting blood volume) in the cerebellar vermis than in non-maltreated women, which correlated strongly with Limbic System Checklist ratings of temporal lobe epilepsy and their frequency of substance use [ 236 ]. In studies of carefully characterized healthy adults who only experienced corporal punishment without other forms of maltreatment, T2 relaxation times were increased in dopamine-rich brain decision making and reward regions (caudate and putamen, dorsolateral prefrontal cortex, substantia nigra, thalamus and accumbens)[ 237 ]. In the latter study, regional T2 relaxation times were significantly associated with increased use of drugs and alcohol. These studies provide further evidence that specific types of abuse and neglect contribute to the intergenerational cycle of emotional and behavioral problems as well as addiction by their detrimental impact on the brain.

Genetic factors interact with childhood trauma to influence brain structure and function. For example, adults with the Val66MET polymorphism of brain-derived neurotrophic factor (BDNF) who had a history of child maltreatment had a greater likelihood of depressive disorders and a smaller hippocampus, highlighting a child trauma x polymorphism interaction for hippocampal volume reductions [ 238 ]. Epigenetic factors also play a role in brain function. In a genome-wide study of promoter methylation in individuals with severe abuse during childhood trauma, decreased promoter transcriptional activity associated with decreased hippocampal expression of the Alsin variants were seen [ 239 ]. Adults who were maltreated as children and committed suicide showed similar hypermethylation in the nerve growth factor-induced protein A binding site within a glucocorticoid receptor variant that was associated with decreased glucocorticoid receptor expression in the hippocampus [ 101 ]. Mice without the expression of the Alsin gene exhibited more anxiety compared to wild type mice [ 240 ].

Furthermore, there are gender x maltreatment effects on brain development. Gender differences were demonstrated using anatomical MRI. Maltreated boys with PTSD had smaller cerebral volumes and larger lateral ventricular volumes than maltreated girls with PTSD, even though the two groups had similar trauma, mental health histories, and IQ [ 212 ]. In addition, research has shown a relationship between the type of trauma and gender, as neglect has been shown to have a strong association with smaller corpus callosum size in boys, while sexual abuse was strongly linked to decreased corpus callosum size in girls [ 217 ]. In a functional MRI study comparing maltreated youth with PTSD symptoms to non-maltreated youth during performance on an emotional oddball task, left precuneus/posterior middle cingulate hypoactivation to fear versus calm or scrambled face targets were seen in maltreated versus control males and may represent dysfunction and less resilience in attentional networks in maltreated males[ 241 ]. These findings were not seen in maltreated females with PTSD symptoms and gender by maltreatment effects were not attributable to demographic, clinical, or maltreatment parameters, suggesting that maltreated males may be dedicating significant functional neural resources to processing affective stimuli in lieu of cognitive processes, which may lead to impulsive decision-making during states of fear emotion and thus less resilience in maltreated males [ 241 ].

Thus, the data to date strongly suggests that childhood trauma is associated with adverse brain development in multiple brain regions that negatively impact emotional and behavioral regulation, motivation, and cognitive function. Molecular aging may contribute to these mechanisms and lead to a premature aging but less than optimal brain maturation process in traumatized children as they become adults.

v. Clinical practice application

Understanding the biological effects of maltreatment provide important information that can be used in practice. The first approach is to ensure a safe environment for the child and adolescent patient. It is unlikely that any treatment or buffering of the biological stress systems will occur if a child continues to live in an extremely adverse environment. As outlined in this volume , evidence based interventions show promise in treating traumatized children. Similar interventions have not only shown promise in treating traumatized adults but have showed that the treatment “heals” some of the dysregulations we reviewed in neurobiological stress systems. Many of victims of trauma have sleep problems [ 242 , 243 ]. In a longitudinal investigation of sexually abused girls, self-reported sleep disturbances were seen approximately 10 years post abuse disclosure, compared to control girls, and were related to current depression, PTSD and revictimization [ 244 ]. It was recently demonstrated that sleep has a restorative function; as during sleep potentially neurotoxic waste products (e.g., beta-amyloid) are cleared from the brain [ 245 ]. Furthermore, inhibition of catecholamines enhance this waste removal [ 245 ]. Therefore, a first step in helping patients with trauma symptoms is to address any sleep hygiene issues they may have, with behavioral methods and/or medications if needed.

A review of recent functional MRI studies demonstrated that cognitive-behavioral therapy can alleviate dysregulation of the fear response and negative emotions associated with anxiety disorders and predict treatment outcomes [ 246 ]. Furthermore, greater left amygdala activity on fMRI in pediatric patients with non-trauma related anxiety was associated with greater improvement in anxiety symptoms post treatment [ 247 ]. Evidenced-based trauma therapies likely work by changing brain responses. However, studies of brain function and trauma in pediatric patients are in their infancy. Psychopharmacological treatments that target biological stress systems are beyond the scope of this article [ 248 , 249 ]. Cognitive-behavioral therapy is the treatment of choice with the most evidenced-based studies suggesting its effects in children. Most child psychiatrists start with sleep hygiene, then a selective serotonin reuptake inhibitor for symptoms of anxiety and depression or an adrenergic agent such as clonidine, propranolol, and guanfacine to down-regulate biological stress systems, if trauma-focus cognitive behavioral therapy and improved sleep have less than optimal results. Other medications are used to treat co-morbid disorders such as attention deficit hyperactivity disorder. Because some childhood traumas (child maltreatment) are associated with family histories of mood and anxiety disorders, clinicians should be careful with anti-psychotic drugs as they may be more likely to cause tardive dyskinesia in these child victims [ 248 ]. Although medications are useful for treating certain symptoms, double blind studies are needed. It is likely that with further imaging and genetic studies, specific treatments and medication regimens may be tailored for specific PTSD symptoms and individuals in the future. However, the biological effects of PTSD and its treatment continue to be understudied.

vi. Important tools for practice

Understanding the biological effects of maltreatment provides important tools one can useful in practice. Besides self-report instruments to study changes in moods, emotions, and behaviors during psychotherapeutic and/or pharmacological treatments, sleep can be objectively measured using bio-markers such as actographs, which are non-invasive digital monitoring devices that can be worn on the wrist and measure daily activity, sleep awakenings, and sleep efficiency. Other bio-markers that can be used to monitor and tailor treatment and help prevent the negative biological effects of trauma are monitoring measures of heart rate, body mass index, and post-trauma and follow-up salivary cortisol and amylase concentrations as these measures predict PTSD [ 250 ], and decreasing these levels during treatment may predict remission.

vii. Future directions

The largest contributor to childhood trauma in the USA is family dysfunction; as almost half of child onset mental disorders and about a third of adult onset mental disorders are preceded by child abuse and neglect, and family dysfunction [ 251 ]. While the mental disorders found in maltreating parents and child victims are serious, they are amenable to prevention and treatment.

Given how detrimental childhood trauma is to an individual's development, more efforts and social resources are needed for prevention. Studies show that child maltreatment is amendable to primary prevention. Child maltreatment prevention programs, such as home visiting [ 252 ] during an expectant mother's first pregnancy, aimed at addressing mental health and parenting concerns of high-risk new mothers, show great promise in preventing child abuse and neglect. For example, home visiting of an expectant mother by nurses for low-income, at-risk families has been a well replicated strategy for preventing child abuse and neglect[ 253 , 254 ]. Several studies of this Nurse-Family Partnership Program have demonstrated: improved grade-point averages and achievement test scores in math and reading in grades 1 through 3 in children during their age 9 follow-up assessment [ 255 ]; decreased internalizing symptoms and decreased rates of tobacco, alcohol, and marijuana use along with improved reading and math scores at age 12 follow-up assessment [ 256 ]; and decreased antisocial behaviors at age 19 follow-up assessment [ 257 ]. However, a when a parent becomes maltreating, even an intensive program of home visitation by nurses in addition to standard treatment is not enough to prevent recidivism of physical abuse and neglect [ 258 ]. Maltreated children in foster care showed less self-destructive behavior, substance use, and total risk behavior problem standardized scores and higher grades than maltreated children who were reunified with their biological families when interviewed during their 6th year follow-up[ 259 ]. These studies indicate that there are two opportunities to break the cycle of maltreatment. The first opportunity is during the expectant parent's first pregnancy, to aid in fostering a loving and caring environment for the parent/child dyad, and to avoid the neurobiological consequences of childhood maltreatment. These types of early prevention programs are cost effective [ 260 ]. However, if this cannot be done, the second opportunity is to treat victims of maltreatment after the fact.

There are important evidence-based interventions (e.g., trauma-focused cognitive behavior therapy) for the treatment of PTSD and depression [ 261 ] and for antisocial behaviors in youth with early trauma (e.g., multisystemic therapy [ 262 ]). Many of these interventions are in other articles within this issue. However, we do not know the long term effectiveness of these programs. We do not have enough professionals trained in evidence-based practices to treat all child victims, and some youth and their families are simply non-complaint with these treatments. Therefore, we still need to understand the neurobiological consequences of chronic stress on a child's developing brain and body so that we can treat the adverse medical and mental health outcomes of early life stress [ 263 ]. A society that places its focus on an infrastructure of primary prevention would be choosing the less costly option for victims and for itself.

viii. Conclusions

We outlined how childhood trauma has detrimental consequences on the biological stress systems, and cognitive and brain development. Trauma in childhood is costly for its victims and for society. Resilience is not a common outcome of childhood trauma. In a longitudinal study of individuals who had experienced abuse and neglect during childhood, only 22% of those who had been abused or neglected achieved resiliency based on a comprehensive assessment of healthy adult functioning, by the time they reached young adulthood [ 264 ]. Females who grew up in poverty and were not maltreated were more likely to show resilience [ 264 ]. While we have some important evidenced-based treatments for child victims, it is in our interest to put in place a national infrastructure of primary child trauma prevention as the less costly option for future victims and for society. Understanding the neurobiological consequences of child trauma will assist in treating child and adult victims, who tend to be more treatment refractory and may have a different endophenotype, than individuals with medical (including mental health) disorders who do not have such histories. Nevertheless, more work is needed to understand the neurobiological consequences of chronic stress on a child's developing brain and body so that we can treat the adverse medical and mental health outcomes of early life stress in those cases (e.g., warfare, natural disasters, child maltreatment) where prevention and effective early intervention may not occur. Such understanding of the neurobiology and genetic influences of child trauma on child development will lead to novel and effective approaches to treatments (e.g., personalized medicine).

  • Trauma in childhood is a grave psychosocial, medical, and public policy problem that has serious consequences for its victims and for society.
  • Chronic interpersonal violence in children is common worldwide.
  • Developmental traumatology, the systemic investigation of the psychiatric and psychobiological effects of chronic overwhelming stress on the developing child, provides a framework and principles when empirically examining the neurobiological effects of pediatric trauma.
  • Despite the widespread prevalence of childhood trauma, less is known about trauma's biological effects in children as compared to adults with child trauma histories; and even less is known about how these pediatric mechanisms underlie trauma's short-term and long-term medical and mental health consequences.

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COMMENTS

  1. Trauma and Public Mental Health: A Focused Review

    Introduction Psychological trauma has developed into a very popular concept in the scientific community, in the world of mental health care, as well as in common language and mass media. The consequences of various shocking events—violence, disasters, acts of terrorism, accidents, and war—receive frequent and enduring attention.

  2. Understanding the Impact of Trauma

    Trauma, including one-time, multiple, or long-lasting repetitive events, affects everyone differently. Some individuals may clearly display criteria associated with posttraumatic stress disorder (PTSD), but many more individuals will exhibit resilient responses or brief subclinical symptoms or consequences that fall outside of diagnostic criteria.

  3. Psychological Trauma: Theory, Research, Practice, and Policy

    The journal publishes empirical research on a wide range of trauma-related topics, including: Psychological treatments and effects Promotion of education about effects of and treatment for trauma Assessment and diagnosis of trauma Pathophysiology of trauma reactions Health services (delivery of services to trauma populations)

  4. Trauma, Resilience, Anxiety Disorders, and PTSD

    The trauma associated with being gravely ill with COVID-19. Prolonged physical separation and social isolation from family and friends. Disruption of regular routines, including work and school for children. Losses of jobs, business failures, and the profound economic consequences. Lack of trust in leadership to effectively deal with the crisis.

  5. Trauma informed interventions: A systematic review

    Trauma informed interventions significantly reduced PTSD symptoms in 11 of 23 studies. Fifteen studies found improvements in three main psychological outcomes including PTSD symptoms (11 of 23), depression (9 of 16), and anxiety (5 of 10).

  6. Trauma treatment: The need for ongoing innovation.

    Trauma treatment: The need for ongoing innovation. © 2019 American Psychological Association . 3, 133-138 Innovations in Treatment of Post-Traumatic Stress Disorder (PTSD) ( Laura S. Brown and Christine A. Courtois) Trauma Treatment: The Need for Ongoing Innovation Laura S. Brown, Christine A. Courtois Independent Practice, Seattle, Washington

  7. Trauma informed interventions: A systematic review

    Trauma informed interventions significantly reduced PTSD symptoms in 11 of 23 studies. Fifteen studies found improvements in three main psychological outcomes including PTSD symptoms (11 of 23), depression (9 of 16), and anxiety (5 of 10).

  8. Exploring the impact of trauma type and extent of exposure on ...

    The long-term behavioral, psychological, and neurobiological effects of exposure to potentially traumatic events vary within the human population. Studies conducted on trauma-exposed human ...

  9. Journal of Traumatic Stress

    Journal of Traumatic Stress is an interdisciplinary forum for the publication of peer-reviewed original papers on biopsychosocial aspects of trauma. Papers focus on theoretical formulations, research, treatment, prevention education/training, and legal and policy concerns. It is the official publication of the International Society for ...

  10. Trauma and resilience informed research principles and practice: A

    Trauma, socio-economic, cultural and structural issues are associated with poor outcomes for most health conditions and may also make research participation difficult and onerous, perpetuating intervention-generated inequalities by generating evidence from those least in need.

  11. The epidemiology of trauma and post-traumatic stress disorder in a

    We found that 642 (31·1%) of 2064 participants reported trauma exposure and 160 (7·8%) of 2063 experienced PTSD by age 18 years. Trauma-exposed participants had high rates of psychopathology (187 [29·2%] of 641 for major depressive episode, 146 [22·9%] of 638 for conduct disorder, and 102 [15·9%] of 641 for alcohol dependence), risk events (160 [25·0%] of 641 for self-harm, 53 [8·3%] of ...

  12. The impact of childhood trauma on children's wellbeing and adult

    The research implied that drug and alcohol misuse can be coping mechanisms of childhood trauma victims as it was reported that all participants mentioned that clients use alcohol and drugs to cope (however, not all statements could be included in this article).

  13. Trauma Through the Life Cycle: A Review of Current Literature

    This paper provides an overview of common traumatic events and responses, with a specific focus on the life cycle. It identifies selected "large T" and "micro" traumas encountered during childhood, adulthood and late life, and the concept of resilience. It also identifies the differences in traumatic events and reactions experienced by men compared to women, those related to the ...

  14. Childhood trauma and adult mental disorder: A systematic ...

    There is strong evidence of an association between childhood trauma and later mental illness. This association is particularly evident for exposure to bullying, emotional abuse, maltreatment and parental loss. The evidence suggests that childhood and adolescence are an important time for risk for la …

  15. A Review of the Literature

    A study of 1,386 patients at a trauma clinic found that patients were significantly more likely to screen positive for probably developing PTSD (in a screen that occurred a mean of 24 days after the traumatic event) if they were under 55 years old, were female, had sustained a blunt or penetrating wound (excluding self-inflicted or accidental wo...

  16. Trauma: Sage Journals

    Trauma is a peer reviewed scholarly journal which brings together a wide range of topics of interest to all those involved in the management of trauma patients. Authoritative reviews of all aspects of trauma care are included: Prevention through prehospital management, accident and emergency medicine, surgery, anaesthetics and intensive care, physical and psychiatric rehabilitation.

  17. A Scoping Review of Vicarious Trauma Interventions for Service

    Health and human service providers who aid traumatized individuals frequently experience vicarious trauma (VT). Although VT plays a critical role in service providers' mental health and well-being, as well as in the quality of their service provision, little information is available concerning the development and implementation of VT interventions for service providers.

  18. Trauma-informed care in the UK: where are we? A qualitative study of

    15 Altmetric Metrics Abstract Background Trauma-informed (TI) approach is a framework for a system change intervention that transforms the organizational culture and practices to address the high prevalence and impact of trauma on patients and healthcare professionals, and prevents re-traumatization in healthcare services.

  19. Call for papers: Trauma in the modern age of technology

    A call for papers from the APA journal Psychological Trauma: Theory, Research, Practice, and Policy for a special issue that seeks to explore, understand, and present both the positive and negative impacts of modern technology on human mental health, specifically looking through the focal lens of trauma.

  20. (PDF) Trauma, Identity and Culture: An Interdisciplinary and

    This paper illustrates such experiences of trauma and their impact on the human psyche by comparatively analyzing (con)texts and selves from the Indian culture and the world. Discover the...

  21. Intergenerational Transmission of Trauma: The Mediating Effects of

    1. Introduction The American Psychological Association defines trauma as "an emotional response to a terrible event" [ 1 ]. Types of trauma are generally separated into two categories: interpersonal (e.g., abuse) and non-interpersonal (e.g., natural disasters or accidents) [ 2 ].

  22. Trauma and Stress

    About 8% of people who have experienced trauma go on to develop PTSD in the course of their lifetime. 1 A person with PTSD has repeated disturbing thoughts and flashbacks of a dangerous, shocking, or scary event. They may often feel afraid, anxious, angry, or ashamed. Research shows that there is a big overlap between people who have PTSD and those who develop substance use disorders, and many ...

  23. Resilience after trauma: from surviving to thriving

    The second paper, written by Dr. Dennis Charney and his colleague Dr. Brian Iacoviello (Iacoviello & Charney, 2014 ), was inspired by Dr. Charney's moving plenary session that integrated his research on the neurobiology of resilience with real-world examples from his personal interviews with resilient individuals.

  24. Trauma Damages by Martha Chamallas :: SSRN

    Although trauma would seem to have everything to do with tort law, not much attention has been paid to trauma and its connection to torts, either with respect to substantive claims or remedies. ... Chamallas, Martha, Trauma Damages (February 13, 2024). Ohio State Legal Studies Research Paper No. 825, 52 Sw. L Rev. (forthcoming 2023), Available ...

  25. "The Biological Effects of Childhood Trauma"

    Trauma in childhood is a grave psychosocial, medical, and public policy problem that has serious consequences for its victims and for society. Chronic interpersonal violence in children is common worldwide.