No association between war-related trauma or PTSD symptom severity and epigenome-wide DNA methylation in Burundian refugees

Background: Depression is frequently comorbid with posttraumatic stress disorder (PTSD) and substantially influences its severity, course and outcomes. Published studies linking war-related paediatric PTSD and Major depressive disorder (MDD) were mainly based on cross-sectional studies. Objective: To prospectively examine the role of PTSD and other risk/protective factors in the development of depression among adolescents with war-related trauma. Methods: A longitudinal study of 160 adolescents aged 15–17 years with war-related trauma and displacement due to war in Eastern Ukraine was performed. Of the 160 adolescents, N = 86 met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-4) criteria for PTSD. All adolescents underwent comprehensive psychiatric assessments that included Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version (K-SADS-PL) administered to both parents and children. Traumatic exposure was assessed using the modified Traumatic Events Screening Inventory for children (TESI-C). PTSD and MDD were assessed with the Clinician-Administered PTSD Scale for Children and Adolescents (CAPS-CA) and Children’s Depression Rating Scale-Revised (CDRS-R), and diagnosed using DSM-4 criteria. Follow-up and repeated measurements occurred at 6 and 12 months. During the study, adolescents requiring clinical care were referred for best available care in the community. Results: Among 92.6% of study completers, 26/79 youth with PTSD developed MDD (32.9%), compared to 6/70 without PTSD (8.5%): relative risk (RR) = 3.83 (95% CI 1.67-8.78), p = 0.0014; Number needed to harm (NNTH) = 4.108 (8.53–2.7). Using logistic regression, variables of school attendance, ‘secondary’ traumatic exposure, and treatment with Trauma-focused Cognitive Behavioral Therapy (TF-CBT) were significantly correlated with the incidence of new-onset depression among adolescents with PTSD. Conclusions: War-related trauma with subsequent PTSD appears to be a significant risk factor for the later development of depression in adolescents. The role of PTSD as a moderator of depression merits further investigation in larger scale longitudinal studies in diverse populations.

The aim of this study is to investigate the association of gene variations of the monoamine oxidase A (MAOA) and the serotonin transporter solute carrier family 6 member 4 (SLC6A4) gene with posttraumatic stress disorder (PTSD) severity and coping strategies in patients with war related PTSD. The study included 747 individuals who had experienced war trauma in the South Eastern Europe conflicts between 1991 and 1999. Genotyping of the MAOA VNTR and SLC6A4 tandem repeat polymorphism in combination with rs25531 was done in 719 participants: 232 females and 487 males. Among them, 369 have had current or lifetime PTSD and 350 have had no PTSD symptoms. For psychometric approach we used the Clinician Administrated PTSD Scale (CAPS), the Brief Symptom Inventory (BSI), the adapted Hoffman-Lazarus Coping scale and a basic socio-demographic data questionnaire. There were no significant intergroup (PTSD versus non PTSD) differences in the genotype distribution of MAOA and SLC6A4 gene polymorphisms. The primary finding of our study was that the MAOA short allele (MAOA-S) was nominally significantly associated with the severity of PTSD symptoms in the total subgroup of participants with lifetime PTSD; males for symptoms of hyperarrousal and females with symptoms of re-experience and hyperarousal. In our research the male subsample with current PTSD and MAOA-S genotype had nominally significantly higher scores for some positive coping strategies compared to those carrying the long allele genotype (MAOA-L). There was no significant association between the severity of PTSD symptoms, BSI phenotype, coping scores and the SLC6A4 genotype. The present results support the notion that MAOA VNTR gene variation modulates development and recovery of posttraumatic stress disorder in a war traumatised population, but did not support a connection between SLC6A4 gene variations and war related PTSD.

Background Depression is frequently comorbid with posttraumatic stress disorder (PTSD) and substantially influences its severity, course and outcomes. Published studies linking war-related paediatric PTSD and Major depressive disorder (MDD) were mainly based on cross-sectional studies. Objective To prospectively examine the role of PTSD and other risk/protective factors in the development of depression among adolescents with war-related trauma. Methods A longitudinal study of 160 adolescents aged 15–17 years with war-related trauma and displacement due to war in Eastern Ukraine was performed. Of the 160 adolescents, N = 86 met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-4) criteria for PTSD. All adolescents underwent comprehensive psychiatric assessments that included Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version (K-SADS-PL) administered to both parents and children. Traumatic exposure was assessed using the modified Traumatic Events Screening Inventory for children (TESI-C). PTSD and MDD were assessed with the Clinician-Administered PTSD Scale for Children and Adolescents (CAPS-CA) and Children's Depression Rating Scale-Revised (CDRS-R), and diagnosed using DSM-4 criteria. Follow-up and repeated measurements occurred at 6 and 12 months. During the study, adolescents requiring clinical care were referred for best available care in the community. Results Among 92.6% of study completers, 26/79 youth with PTSD developed MDD (32.9%), compared to 6/70 without PTSD (8.5%): relative risk (RR) = 3.83 (95% CI 1.67–8.78), p = 0.0014; Number needed to harm (NNTH) = 4.108 (8.53–2.7). Using logistic regression, variables of school attendance, ‘secondary’ traumatic exposure, and treatment with Trauma-focused Cognitive Behavioral Therapy (TF-CBT) were significantly correlated with the incidence of new-onset depression among adolescents with PTSD. Conclusions War-related trauma with subsequent PTSD appears to be a significant risk factor for the later development of depression in adolescents. The role of PTSD as a moderator of depression merits further investigation in larger scale longitudinal studies in diverse populations.

The aim of the current study was to examine the relations among mindfulness, posttraumatic stress disorder (PTSD) symptom severity, and stressful life events (SLEs) in African-American urban adolescents. Another aim was to examine mindfulness as a moderator of the relation between SLEs and PTSD symptom severity in this population. Eighty-eight African-American high school students from a low-income urban community completed measures of demographics, PTSD symptom severity, SLEs, and mindfulness. Mindfulness was significantly negatively related to PTSD symptom severity, r(86) = -.70, p < .001, 95% CI [-.58, -79], and SLEs were significantly positively related to PTSD symptom severity, r(86) = .29, p = .003, 95% CI [.09, .47]. Mindfulness was an independent predictor of PTSD symptom severity after accounting for SLEs, B = -1.16, t(84) = -9.06, p < .001, 95% CI [-1.41, -0.90], and SLEs were an independent predictor of PTSD symptom severity after accounting for mindfulness, B = 0.49, t(84) = 2.92, p = .004, 95% CI [0.16, 0.82]. Mindfulness did not moderate the relation between SLEs and PTSD symptom severity, B = -.003, t(84) = -0.15, p = .89, 95% CI [-.04, .03]. This study has implications for both mindfulness as a potential protective factor against PTSD symptom severity and SLEs as a potential risk factor for increased PTSD symptom severity in African-American urban adolescents.

Background: Exposure to adversity in utero is thought to increase susceptibility to develop posttraumatic stress disorder (PTSD) following later life trauma, due to neurobiological programming effects during critical developmental periods. It remains unknown whether effects of prenatal adversity on PTSD susceptibility are modulated by genetic variations in neurobiological pathways implicated in PTSD susceptibility. Objective: We investigated whether genetic variation in the glucocorticoid receptor (GR) modulated effects of prenatal famine exposure on late adulthood PTSD symptom severity after trauma exposure in childhood and mid-to-late adulthood. Method: We included N = 439 term-born singleton adults (mean age: 72 years, 54.2% women) from the Dutch Famine Birth Cohort, born around the time of the Dutch Famine of 1944/1945, divided into exposure and control groups based on timing of the famine during gestation. Participants filled out self-report questionnaires on childhood (Childhood Trauma Questionnaire) and mid-to-late adulthood (Life Events Checklist for DSM-5) trauma, and current PTSD symptom severity (PTSD Checklist for DSM-5). GR haplotypes were determined from four functional GR single nucleotide polymorphisms (ER22/23EK, N363S, BclI and exon 9β) in previously collected DNA. Linear regression analyses were performed to investigate associations of GR haplotype and prenatal famine exposure in conjunction with later life trauma on PTSD symptom severity. Results: We observed a significant three-way interaction between the GR Bcll haplotype, famine exposure during early gestation, and adulthood trauma exposure on PTSD symptom severity in late adulthood. Only participants exposed to famine during early gestation without the GR Bcll haplotype showed a significantly stronger positive association between adulthood trauma and PTSD symptom severity than non-exposed participants, indicating increased PTSD susceptibility. Conclusions: Our results illustrate the importance of integrated approaches considering genetics and environmental contexts throughout various life periods, including the rarely investigated prenatal environment, to elucidate how PTSD susceptibility evolves throughout life. HIGHLIGHTS Adversity during pregnancy is thought to increase offspring’s PTSD risk following later life trauma, but exact neurobiological mechanisms underlying this process remain unknown. We found that effects of prenatal famine exposure on PTSD symptom severity were influenced by genetic variation in the glucocorticoid receptor, which signals effects of the stress hormone cortisol. Integrated approaches considering genetics and environmental contexts throughout both early and later life are important to understand how PTSD risk evolves throughout life.

Research suggests autistic people experience greater post-traumatic stress disorder symptom severity than non-autistic people following traumatic events. Post-trauma appraisals are fundamental in cognitive models of post-traumatic stress disorder, but have not been explored in autistic people. We aimed to explore whether we could replicate effects of heightened trauma exposure and post-traumatic stress disorder symptom severity in autistic adults, and examine how post-traumatic appraisals affect the association between autism and post-traumatic stress disorder symptom severity. Two hundred forty-two autistic (n = 148) and non-autistic adults (n = 94) completed a survey measuring trauma exposure, post-traumatic stress disorder symptom severity and post-trauma appraisals. Exposure to types of traumatic events did not differ significantly between the groups, but the autistic group endorsed more events that 'happened to me' directly. Post-traumatic stress disorder symptom severity and endorsement of negative post-traumatic appraisals were significantly higher in the autistic group, specifically alienation, shame and fear appraisals. These appraisals mediated the association between autism and post-traumatic stress disorder symptom severity. Therefore, as in the general population, greater endorsement of negative post-traumatic appraisals may be a risk factor for post-traumatic stress disorder symptom development in autistic adults, particularly appraisals of shame, fear and alienation. Longitudinal designs are required to confirm the direction of these effects and to elucidate factors underlying these negative appraisals in autistic people.Lay SummaryMany people experience intrusive memories and anxiety after a traumatic event. However, for some, these symptoms last longer and they might be diagnosed with post-traumatic stress disorder. Research suggests that autistic people might be more likely to develop post-traumatic stress disorder and experience more severe symptoms compared to non-autistic people after traumatic events. One factor that is important in post-traumatic stress disorder development is how people think about the trauma. These might be thoughts like 'It was my fault', 'I'm not safe', 'I'm disconnected from other people'. There has not been research into how autistic people think about traumatic events compared to non-autistic people, and this could be important for making post-traumatic stress disorder treatments more effective for them, as many of these focus on thoughts. In this study, we asked 148 autistic people and 94 non-autistic people in the United Kingdom to complete an online survey about their trauma history, post-traumatic stress disorder symptoms and thoughts about a traumatic event. We found that autistic people experienced more types of traumatic events directly (it happened to them), but they did not experience more types of traumatic events overall. Interestingly, both groups reported events like bullying or the death of a loved one as traumatic, but these events would not meet the official diagnostic criteria for post-traumatic stress disorder. As expected, autistic people reported worse post-traumatic stress disorder symptoms than non-autistic people and were more likely to meet the cut-off for post-traumatic stress disorder diagnosis. Autistic people also reported more negative thoughts about the trauma, especially feeling unsafe, disconnected, ashamed or that the trauma was their fault. Having more thoughts like this was associated with being autistic and experiencing more severe post-traumatic stress disorder symptoms. Our findings suggest that therapies focusing on these negative thoughts could be helpful for autistic people with post-traumatic stress disorder. Future research should explore why autistic people have more of these thoughts after traumatic events and should use longitudinal or experimental designs to explore how these factors influence one another over time. Efforts to prevent negative experiences, challenge negative attitudes in society towards autism and support positive autistic identity and well-being will be helpful for changing this in the future. It is also important that mental health services offer support for post-traumatic stress disorder even when events do not meet the current diagnostic criteria, as this might prevent autistic and non-autistic people who need support with post-traumatic stress disorder getting help.

PTSD and Combat-Related Injuries: Functional Neuroanatomy

The diagnostic criteria for posttraumatic stress disorder (PTSD) have received significant scrutiny. Several studies have investigated the utility of Criterion A2, the subjective emotional response to a traumatic event. The American Psychiatric Association (APA) has proposed elimination of A2 from the PTSD diagnostic criteria for DSM-5; however, there is mixed support for this recommendation and few studies have examined A2 in samples at high risk for PTSD such as veterans. In the current study of 908 veterans who screened positive for a traumatic event, A2 was not significantly associated with having been told by a doctor that the veteran had PTSD. Those who endorsed A2, however, reported greater PTSD symptom severity in the 3 DSM-IV symptom clusters of reexperiencing (d = 0.45), avoidance (d = 0.61), and hyperarousal (d = 0.44), and A2 was significantly associated with PTSD symptom severity for all 3 clusters (R(2) = .25, .25, and .27, respectively) even with trauma exposure in the model. Thus, although A2 may not be a necessary criterion for PTSD diagnosis, its association with PTSD symptom severity warrants further exploration of its utility.

Animal and human research suggests that the development of posttraumatic stress disorder (PTSD) may involve the overconsolidation of memories of a traumatic experience. Previous studies have attempted to use pharmaceutical agents, especially the β-adrenergic blocker propranolol, to reduce this overconsolidation. In this randomized, placebo-controlled study of the efficacy of propranolol in reducing the development of PTSD, we optimized dosages and conducted both psychophysiological and clinical assessments 1 and 3 months after the traumatic event. Forty-one emergency department patients who had experienced a qualifying acute psychological trauma were randomized to receive up to 240 mg/day of propranolol or placebo for 19 days. At 4 and 12 weeks post-trauma, PTSD symptoms were assessed. One week later, participants engaged in script-driven imagery of their traumatic event while psychophysiological responses were measured. Physiological reactivity during script-driven traumatic imagery, severity of PTSD symptoms, and the rate of the PTSD diagnostic outcome were not significantly different between the two groups. However, post hoc subgroup analyses showed that in participants with high drug adherence, at the 5-week posttrauma assessment, physiological reactivity was significantly lower during script-driven imagery in the propranolol than in the placebo subjects. The physiological results provide some limited support for a model of PTSD in which a traumatic conditioned response is reduced by posttrauma propranolol. However, the clinical results from this study do not support the preventive use of propranolol in the acute aftermath of a traumatic event.

Background Learning tasks have been used to predict why some, and not others, develop posttraumatic stress disorder (PTSD) after exposure to a traumatic event. There is some evidence from prospective studies in high risk profession samples that reduced extinction learning might represent a marker or even a vulnerability factor for PTSD development. Objective Since the evidence is scarce, the aim of this study was to perform a conceptual replication of an earlier prospective study, testing whether pretrauma extinction learning predicts later PTSD symptom severity. Method A sample of 529 fire fighters performed a conditioning task at baseline and filled out questionnaires to assess PTSD symptom severity and neuroticism. At six and 12 months follow-up, exposure to stressful events and PTSD symptom severity were measured. Results Results indicate that previous findings were not replicated: although reduced extinction learning was associated with higher PTSD symptom severity at baseline, extinction learning did not predict PTSD symptom severity at follow-up. Only PTSD symptom severity at baseline and stressor severity predicted PTSD symptom severity at follow-up. Conclusions Since earlier findings on the predictive value of pre-trauma extinction learning on PTSD symptom severity were not replicated, extinction learning might not be a general risk factor PTSD for all individuals. More prospective studies including multiple factors seem needed to unravel the complex relationships of these factors influencing PTSD development. HIGHLIGHTS Reduced extinction learning correlated with higher PTSD symptom severity at baseline. Reduced extinction learning did not predict PTSD symptom severity at follow-up. The predictive effect of pre-trauma extinction learning on PTSD was not replicated

Introduction: Cardiovascular disease (CVD) remains the leading cause of death among women in the United States. Although premenopausal women are thought to be protected from CVD, trauma exposure increases their CVD risk. Poor sleep – a CVD risk factor – is common after trauma exposure. Further, accumulating evidence suggests that vascular dysfunction is independently associated with CVD. However, the link between sleep and vascular function in otherwise healthy, trauma-exposed young women is not known. Therefore, the purpose of the present study was to investigate the individual and combined effects of sleep quality and post-traumatic stress disorder (PTSD) symptom severity on endothelial function and arterial stiffness. Methods: We recruited 42 otherwise healthy women (18 –­ 40 years) from diverse backgrounds who had been exposed to trauma. We successfully collected data on sleep, vascular function, depression and PTSD symptom severity in 35 women, across two visits. Sleep efficiency (SE) was objectively measured as the relative time (%) spent asleep while in bed, using wrist actigraphy. Participants wore the ActiWatch for seven days between visits. During visit one, PTSD symptom severity was assessed using the PTSD checklist for DSM 5 (PCL5) and depressive symptom severity with the Beck Depression Inventory (BDI). At visit two, we assessed endothelial function via reactive hyperemia index (RHI) using peripheral arterial tone and arterial stiffness via pulse wave velocity (PWV) using applanation tonometry. Results: Participants’ mean age and body mass index (BMI) were 27±7 years and 27±6 kg/m2 respectively. Mean systolic and diastolic blood pressures were 103±9 and 67±8 mmHg respectively, and heart rate was 74±12 bpm. SE was positively correlated with RHI (r=0.35, p=0.019), and negatively correlated with PWV (r=-0.46, p=0.004). PCL5 score was negatively correlated with RHI (r=-0.52, p&lt;0.001), and not PWV (r=0.12, p=0.253). Additionally, a positive association was observed between age and PWV (r=0.50, p=0.001). BDI score was only correlated with PCL5 (r=0.60, p&lt;0.001). Next, to explore the predictive value of SE and PCL5 on RHI and PWV, we conducted separate multiple linear regression models with SE, PCL5 scores and age as predictors. The model predicting RHI was significant (R2=0.48, p&lt;0.001), with PCL5 emerging as the strongest predictor (β=-0.56, p&lt;0.001). Similarly, the model predicting PWV was significant (R2=0.45, p&lt;0.001), with both SE and age as the strongest predictors (β=-0.44, p=0.004 and β=0.49, p=0.001, respectively). Conclusion: Our results suggest that poor sleep may contribute to increased arterial stiffness after trauma exposure, while endothelial dysfunction could be driven by PTSD symptom severity. These findings could serve to distinguish trauma-exposed women at risk of CVD and identify specific interventions (i.e., targeting sleep efficiency or PTSD symptoms) to prevent or delay vascular dysfunction. UL1TR002494, NIH K01HL161027 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

There is concern that exposure therapy, an evidence-based cognitive-behavioral treatment for posttraumatic stress disorder (PTSD), may be inappropriate because of risk of relapse for patients with co-occurring substance dependence. To determine whether an integrated treatment for PTSD and substance dependence, Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE), can achieve greater reductions in PTSD and substance dependence symptom severity compared with usual treatment for substance dependence. Randomized controlled trial enrolling 103 participants who met DSM-IV-TR criteria for both PTSD and substance dependence. Participants were recruited from 2007-2009 in Sydney, Australia; outcomes were assessed at 9 months postbaseline, with interim measures collected at 6 weeks and 3 months postbaseline. Participants were randomized to receive COPE plus usual treatment (n = 55) or usual treatment alone (control) (n = 48). COPE consists of 13 individual 90-minute sessions (ie, 19.5 hours) with a clinical psychologist. Change in PTSD symptom severity as measured by the Clinician-Administered PTSD Scale (CAPS; scale range, 0-240) and change in severity of substance dependence as measured by the number of dependence criteria met according to the Composite International Diagnostic Interview version 3.0 (CIDI; range, 0-7), from baseline to 9-month follow-up. A change of 15 points on the CAPS scale and 1 dependence criterion on the CIDI were considered clinically significant. From baseline to 9-month follow-up, significant reductions in PTSD symptom severity were found for both the treatment group (mean difference, -38.24 [95% CI, -47.93 to -28.54]) and the control group (mean difference, -22.14 [95% CI, -30.33 to -13.95]); however, the treatment group demonstrated a significantly greater reduction in PTSD symptom severity (mean difference, -16.09 [95% CI, -29.00 to -3.19]). No significant between-group difference was found in relation to improvement in severity of substance dependence (0.43 vs 0.52; incidence rate ratio, 0.85 [95% CI, 0.60 to 1.21), nor were there any significant between-group differences in relation to changes in substance use, depression, or anxiety. Among patients with PTSD and substance dependence, the combined use of COPE plus usual treatment, compared with usual treatment alone, resulted in improvement in PTSD symptom severity without an increase in severity of substance dependence. isrctn.org Identifier: ISRCTN12908171.

Post-traumatic stress disorder (PTSD) is a heterogeneous mental health condition, characterized by diverse symptom profiles and biological underpinnings. A dissociative subtype of PTSD has been identified, though the potential risk factors and underlying neurobiology are yet to be understood. The current study comprised Canadian Armed Forces (CAF) members and Veterans with a history of deployment, and with diagnoses of non-dissociative (n = 31) and dissociative subtypes of PTSD (n = 19), in addition to non-deployed healthy controls (n = 14). Participants completed questionnaires assessing clinical symptoms and experiences of trauma, and provided saliva and blood samples for cortisol and inflammatory marker assessments. Individuals with dissociative PTSD displayed elevated PTSD and depression symptom severity, and greater reports of specific forms of childhood trauma compared to individuals with non-dissociative PTSD and controls. Morning cortisol was elevated in both PTSD groups compared to controls, however the PTSD groups did not differ from one another. Evening cortisol concentrations were elevated in both PTSD groups compared to controls, and in the dissociative PTSD subtype compared to the non-dissociative PTSD subtype when controlling for depression symptoms. PTSD diagnostic group moderated the relationship between awakening cortisol levels and PTSD symptom severity, such that the non-dissociative PTSD group displayed a negative correlation between awakening cortisol levels and PTSD symptom severity, while no significant relation was identified in the dissociative PTSD group. C-reactive protein (CRP) levels did not differ across diagnostic groups when accounting for body mass index (BMI). However, CRP positively correlated with depressive symptoms only among individuals with dissociative PTSD. Together, examining PTSD subtypes may help inform more effective and personalized treatment strategies in the future.

Posttraumatic stress disorder and epigenetic signatures of inflammation in middle-aged women.

Serum brain-derived neurotrophic factor remains elevated after long term follow-up of combat veterans with chronic post-traumatic stress disorder