Effects of prenatal exposure to the 1944–45 Dutch famine and glucocorticoid receptor polymorphisms on later life PTSD susceptibility

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<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<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<0.001), with PCL5 emerging as the strongest predictor (β=-0.56, p<0.001). Similarly, the model predicting PWV was significant (R2=0.45, p<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.

A - 125 Posttraumatic Stress Disorder Symptom Severity and its Relationship to Performance on the Test of Memory Malingering in a Veteran Sample.

Effect of agreement between clinician-rated and patient-reported PTSD symptoms on intensive outpatient treatment outcomes

Evidence describing the association between sleep quality and trauma-focused therapy is mixed. This secondary analysis of a primary care sample examined whether (a) baseline sleep quality moderated posttraumatic stress disorder (PTSD) symptom severity over time across groups receiving different doses of cognitive processing therapy (CPT) and (b) sleep quality improved over time with CPT. Participants were 227 adults who screened positive for PTSD and were participating in a clinical trial comparing two models of PTSD treatment delivery in primary care. The Pittsburgh Sleep Quality Index (PSQI) and PTSD Checklist for DSM-5 (PCL-5) were used to assess sleep disturbance and PTSD symptom severity, respectively. Multiple linear regression was used to assess whether baseline PSQI scores moderated 12-month PCL-5 scores across CPT dosage groups (0 sessions: 51.1%, 1-7 sessions: 31.7%; ≥ 8 sessions [adequate dose]: 17.2%) and whether PSQI scores differed by group at 12-month follow-up. Post hoc analyses examined changes in PCL-5 sleep disturbance items. Baseline sleep disturbance did not moderate the effect of CPT on PTSD severity among participants with an adequate CPT dose, p>.112.Sleep quality improved with adequate dose, B = -2.63, SE = 0.75,p<.001. Differences in change scores across groups for PCL-5 Item 2,F(2, 435) = 11.34,and Item 20,H(2) = 32.04, indicated that participants with an adequate CPT dose had greater reductions in trauma-related sleep symptoms than those who received 0-7 sessions, ps <.001. Residual post-CPT sleep impairment despite adequate PTSD improvement warrants further interventions.

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.

Introduction: Posttraumatic stress disorder (PTSD) is associated with increased cardiovascular disease (CVD) risk. Sleep disturbances, a known risk factor for CVD, are also a hallmark of PTSD symptoms. Therefore, in a group of premenopausal trauma-exposed women, we aimed to investigate the role of sleep in the relationship between PTSD symptom severity and endothelial function, a determinant of cardiovascular health. We hypothesized that sleep might influence that relationship. Methods: We recruited 44 trauma-exposed women between the ages of 18 to 40 years and conducted a study over two laboratory visits. During visit 1, we collected baseline hemodynamics and assessed PTSD symptom severity using the PTSD checklist for DSM-5 (PCL5), and participants were given an Actigraphy watch to wear for the next 7 days to track their sleep-wake cycle and sleep efficiency. During visit 2, we measured endothelial function via the gold standard technique of flow-mediated dilation (FMD). All recorded vascular variables during FMD were analyzed using specialized semiautomated edge-detection software (Cardiovascular Suite, Quipu srl., Pisa, Italy). Further, FMD was adjusted for shear rate (FMDC) to account for variability in shear stress. For data analysis, we separated our participants into two groups based on median sleep efficiency (%): good sleepers (&gt;83, n=17) and poor sleepers (≤83, n=27). We subsequently subcategorized each “sleepers” group using the median of PCL5 scores (a.u.): low PCL5 (≤36) and high PCL5 (&gt;36). Statistical Analysis: We performed statistical analysis using SPSS version 28.0. First, we ran Pearson’s correlations to probe for the association between PCL5 and FMD within each “sleepers” group. Next, we ran an independent sample t-test to compare mean FMD and mean FMDC between high PCL5 and low PCL5 subgroups. Results: At baseline, both groups were comparable in age, BMI, and resting hemodynamics (p&gt;0.05), except for diastolic blood pressure (p=0.02). As expected, poor sleepers had a lower sleep efficiency compared to good sleepers (78.05 ± 6.75% vs 86.46 ± 1.96%, p&lt;0.001). Next, we found a negative correlation between PCL5 and FMDC in good sleepers (r= -0.36, p=0.08) but not in poor sleepers (r=0.08, p=0.71). Likewise, in good sleepers only, we found lower FMDC in the high PCL5 compared to the low PCL5 subgroup (3.9 ± 8.5% vs 18.1 ± 10.6%, p= 0.012). Conclusion: These preliminary results suggest that sleep might increase CVD risk in premenopausal trauma-exposed women by moderating the relationship between PTSD symptom severity and endothelial function. NIH K01 K01HL161027, NIH R03 R03HL174817, UMN CTSI (UL1TR002494) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

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.

Paeoniflorin exerts anti-PTSD effects in adult rats by modulating hippocampus and amygdala histone acetylation modifications in response to early life stress

A - 129 An Examination of the Relationship between Posttraumatic Stress Disorder Symptom Severity and Cognitive Test Performance in a Veteran Sample.

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.

Many patients are currently unable to access psychological treatments for post-traumatic stress disorder (PTSD), and it is unclear which types of therapist-assisted internet-based treatments work best. We aimed to investigate whether a novel internet-delivered cognitive therapy for PTSD (iCT-PTSD), which implements all procedures of a first-line, trauma-focused intervention recommended by the UK National Institute for Health and Care Excellence (NICE) for PTSD, is superior to internet-delivered stress management therapy for PTSD (iStress-PTSD), a comprehensive cognitive behavioural treatment programme focusing on a wide range of coping skills. We did a single-blind, randomised controlled trial in three locations in the UK. Participants (≥18 years) were recruited from UK National Health Service (NHS) Improving Access to Psychological Therapies (IAPT) services or by self-referral and met DSM-5 criteria for PTSD to single or multiple events. Participants were randomly allocated by a computer programme (3:3:1) to iCT-PTSD, iStress-PTSD, or a 3-month waiting list with usual NHS care, after which patients who still met PTSD criteria were randomly allocated (1:1) to iCT-PTSD or iStress-PTSD. Randomisation was stratified by location, duration of PTSD (<18 months or ≥18 months), and severity of PTSD symptoms (high vs low). iCT-PTSD and iStress-PTSD were delivered online with therapist support by messages and short weekly phone calls over the first 12 weeks (weekly treatment phase), and three phone calls over the next 3 months (booster phase). The primary outcome was the severity of PTSD symptoms at 13 weeks after random assignment, measured by self-report on the PTSD Checklist for DSM-5 (PCL-5), and analysed by intention-to-treat. Safety was assessed in all participants who started treatment. Process analyses investigated acceptability and compliance with treatment, and candidate moderators and mediators of outcome. The trial was prospectively registered with the ISRCTN registry, ISRCTN16806208. Of the 217 participants, 158 (73%) self-reported as female, 57 (26%) as male, and two (1%) as other; 170 (78%) were White British, 20 (9%) were other White, six (3%) were Asian, ten (5%) were Black, eight (4%) had a mixed ethnic background, and three (1%) had other ethnic backgrounds. Mean age was 36·36 years (SD 12·11; range 18-71 years). 52 (24%) participants met self-reported criteria for ICD-11 complex PTSD. Fewer than 10% of participants dropped out of each treatment group. iCT-PTSD was superior to iStress-PTSD in reducing PTSD symptoms, showing an adjusted difference on the PCL-5 of -4·92 (95% CI -8·92 to -0·92; p=0·016; standardised effect size d=0·38 [0·07 to 0·69]) for immediate allocations and -5·82 (-9·59 to -2·04; p=0·0027; d=0·44 [0·15 to 0·72]) for all treatment allocations. Both treatments were superior to the waiting list for PCL-5 at 13 weeks (d=1·67 [1·23 to 2·10] for iCT-PTSD and 1·29 [0·85 to 1·72] for iStress-PTSD). The advantages in outcome for iCT-PTSD were greater for participants with high dissociation or complex PTSD symptoms, and mediation analyses showed both treatments worked by changing negative meanings of the trauma, unhelpful coping, and flashback memories. No serious adverse events were reported. Trauma-focused iCT-PTSD is effective and acceptable to patients with PTSD, and superior to a non-trauma-focused cognitive behavioural stress management therapy, suggesting that iCT-PTSD is an effective way of delivering the contents of CT-PTSD, one of the NICE-recommended first-line treatments for PTSD, while reducing therapist time compared with face-to-face therapy. Wellcome Trust, UK National Institute for Health and Care Research Oxford Health Biomedical Research Centre.

Symptoms of post-traumatic stress disorder (PTSD) are common in military populations, and frequently associated with a history of combat-related mild traumatic brain injury (mTBI). In this study, we examined relationships between severity of PTSD symptoms and levels of extracellular vesicle (EV) proteins and miRNAs measured in the peripheral blood in a cohort of military service members and Veterans (SMs/Vs) with chronic mTBI(s). Participants (n = 144) were divided into groups according to mTBI history and severity of PTSD symptoms on the PTSD Checklist for DSM-5 (PCL-5). We analyzed EV levels of 798 miRNAs (miRNAs) as well as EV and plasma levels of neurofilament light chain (NfL), Tau, Amyloid beta (Aβ) 42, Aβ40, interleukin (IL)-10, IL-6, tumor necrosis factor-alpha (TNFα), and vascular endothelial growth factor (VEGF). We observed that EV levels of neurofilament light chain (NfL) were elevated in participants with more severe PTSD symptoms (PCL-5 ≥ 38) and positive mTBI history, when compared to TBI negative controls (p = 0.024) and mTBI participants with less severe PTSD symptoms (p = 0.006). Levels of EV NfL, plasma NfL, and hsa-miR-139–5p were linked to PCL-5 scores in regression models. Our results suggest that levels of NfL, a marker of axonal damage, are associated with PTSD symptom severity in participants with remote mTBI. Specific miRNAs previously linked to neurodegenerative and inflammatory processes, and glucocorticoid receptor signaling pathways, among others, were also associated with the severity of PTSD symptoms. Our findings provide insights into possible signaling pathways linked to the development of persistent PTSD symptoms after TBI and biological mechanisms underlying susceptibility to PTSD.

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.

Cognitive behavioral interventions delivered via the internet are demonstrably efficacious treatment options for posttraumatic stress disorder (PTSD) in underserved, Arabic-speaking populations. However, the role of specific treatment components remains unclear, particularly in conflict-affected areas of the Middle East and North Africa. This study aims to evaluate 2 brief internet-based treatments in terms of efficacy, including change in PTSD symptom severity during treatment. Both treatments were developed in line with Interapy, an internet-based, therapist-assisted cognitive behavioral therapy protocol for PTSD and adapted to the specific research question. The first treatment comprised self-confrontation and social sharing (exposure treatment; 6 sessions); the second comprised cognitive restructuring and social sharing (cognitive restructuring treatment; 6 sessions). The 2 treatments were compared with each other and with a waitlist control group. In total, 365 Arabic-speaking participants from the Middle East and North Africa (mean age 25.49, SD 6.68 y) with PTSD were allocated to cognitive restructuring treatment (n=118, 32.3%), exposure treatment (n=122, 33.4%), or a waitlist control group (n=125, 34.2%) between February 2021 and December 2022. PTSD symptom severity, posttraumatic maladaptive cognitions, anxiety, depressive and somatoform symptom severity, and quality of life were assessed via self-report at baseline and after treatment or waiting time. PTSD symptom severity was also measured throughout treatment or waiting time. Treatment satisfaction was assessed after treatment completion. Treatment use and satisfaction were compared between the 2 treatment conditions using appropriate statistical tests (eg, chi-square and Welch tests). Multiple imputation was performed to address missing data and evaluate treatment-associated changes. These changes were analyzed using multigroup change modeling in the completer and intention-to-treat samples. Overall, 200 (N=240, 83.3%) participants started any of the treatments, of whom 123 (61.5%) completed the treatment. Treatment condition was not significantly associated with the proportion of participants who started versus did not start treatment (P=.20) or with treatment completion versus treatment dropout (P=.71). High treatment satisfaction was reported, with no significant differences between the treatment conditions (P=.48). In both treatment conditions, PTSD, anxiety, depressive and somatoform symptom severity, and posttraumatic maladaptive cognitions decreased, and quality of life improved significantly from baseline to the posttreatment time point (P≤.001 in all cases). Compared with the baseline assessment, overall PTSD symptom severity decreased significantly after 4 sessions in both treatment conditions (P<.001). Moreover, both treatment conditions were significantly superior to the waitlist control group regarding overall PTSD symptom severity (P<.001) and most other comorbid mental health symptoms (P<.001 to P=.03). Differences between the 2 conditions in the magnitude of change for all outcome measures were nonsignificant. Internet-based cognitive behavioral treatments for PTSD focusing primarily on either self-confrontation or cognitive restructuring are applicable and efficacious for Arabic-speaking participants. German Clinical Trials Register DRKS00010245; https://drks.de/search/de/trial/DRKS00010245.

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