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Although effective evidence-based trauma-focused psychotherapies for posttraumatic stress disorder (PTSD) are available, a significant proportion of patients show a suboptimal response or do not complete them. MDMA-assisted therapy (MDMA-AT) for PTSD is a promising intervention currently being evaluated in numerous studies worldwide, including investigation for potential Food and Drug Administration (FDA) approval in the United States. The concepts of set and setting are foundational in psychedelic therapy and refer to the mindset a person brings to therapy and the environment in which it takes place, respectively. Both are believed to play a critical role in the individual’s experience and efficacy of MDMA-AT. In this article, we describe the importance of set and setting in MDMA-AT for PTSD and outline the advantages and challenges of implementing this novel intervention in large healthcare settings such as the Veterans Health Administration (VHA). Mostly derived from our experience conducting clinical trials of MDMA-AT for PTSD in VHA, we present specific and practical suggestions for optimizing set and setting from both the participant’s and clinician’s perspective in a manner that both leverages the opportunities of such settings and adapts to their challenges. These recommendations are intended to inform future MDMA-AT for PTSD research and, potentially, eventual clinical implementation efforts in traditional healthcare systems.

BackgroundAssociations between childhood trauma, neurodevelopment, alcohol use disorder (AUD), and posttraumatic stress disorder (PTSD) are understudied during adolescence.MethodsUsing 1652 participants (51.75% female, baseline Mage = 14.3) from the Collaborative Study of the Genetics of Alcoholism, we employed latent growth curve models to (1) examine associations of childhood physical, sexual, and non-assaultive trauma (CPAT, CSAT, and CNAT) with repeated measures of alpha band EEG coherence (EEGc), and (2) assess whether EEGc trajectories were associated with AUD and PTSD symptoms. Sex-specific models accommodated sex differences in trauma exposure, AUD prevalence, and neural development.ResultsIn females, CSAT was associated with higher mean levels of EEGc in left frontocentral (LFC, ß = 0.13, p = 0.01) and interhemispheric prefrontal (PFI, ß = 0.16, p < 0.01) regions, but diminished growth in LFC (ß = -0.07, p = 0.02) and PFI (ß = -0.07, p = 0.02). In males, CPAT was associated with lower mean levels (ß = -0.17, p = 0.01) and increased growth (ß = 0.11, p = 0.01) of LFC EEGc. Slope of LFC EEGc was inversely associated with AUD symptoms in females (ß = -1.81, p = 0.01). Intercept of right frontocentral and PFI EEGc were associated with AUD symptoms in males, but in opposite directions. Significant associations between EEGc and PTSD symptoms were also observed in trauma-exposed individuals.ConclusionsChildhood assaultive trauma is associated with changes in frontal alpha EEGc and subsequent AUD and PTSD symptoms, though patterns differ by sex and trauma type. EEGc findings may inform emerging treatments for PTSD and AUD.

BackgroundIdentifying factors associated with post-disaster youth substance use is a crucial element of developing evidence-based prevention and intervention efforts. Hurricane María struck Puerto Rico in September of 2017 and the wide-spread impact from this disaster, including exposure to trauma, displacement, and disrupted social supports had the potential to negatively impact levels of substance use among youth across the archipelago. However, post-disaster substance use remains under-investigated in this context. The current study sought to identify risk and protective factors associated with substance use among Puerto Rican youth in the aftermath of Hurricane Maria.MethodsCross-sectional, secondary data analyses were conducted using school-based survey data collected at all schools in Puerto Rico between February 1 and June 29, 2018 (5-9 months after Hurricane María). Social supports, substance use, and trauma symptoms were assessed. An ordinal regression analysis was conducted to identify student factors associated with greater likelihood of post-disaster substance use.ResultsA total of 36,485 participants (50.7% female, grades 7-12), were included in an ordinal regression analysis that compared the likelihood of respondents endorsing high, low, or no substance use after Hurricane María based on reported adult social support, counselor/teacher social support, peer social support, ptsd symptomatology, and gender. Findings showed that, when compared to students that endorsed low or no substance use, those who reported having adult social support demonstrated a 58% reduction in odds (OR = 0.42, 95% CI: 0.34-0.53) of reporting high substance use after Hurricane María, while students who reported having teacher/counselor social support demonstrated a 21% reduction in odds (OR = 0.79, 95% CI: 0.69-0.89) of reporting high substance use. Additionally, those that reported having peer social support demonstrated a 31% increase in odds (OR = 1.31, 95% CI: 1.10 to 1.58) of reporting higher substance use, compared to those that reported low or no substance use.ConclusionsWhile social support was generally protective, prevention efforts to build positive family and community connections may be indicated. Evidence-based school screenings of substance use and trauma may help direct intervention to those most at risk for co-occurring issues.

ObjectiveExposure to chronic structural stressors (e.g., poverty, community violence, and discrimination) exacerbates posttraumatic stress disorder (PTSD) symptoms and reduces how adolescents benefit from trauma-focused interventions. However, current evidence-based PTSD interventions seldom include concrete guidance regarding how to target chronic structural stressors in care.MethodThis study utilized qualitative thematic analysis of audio-recorded PTSD therapy sessions with 13 racially diverse, low socioeconomic status adolescents to elucidate (a) how often adolescents disclose chronic structural stressors in therapy, (b) the types of chronic structure stressors that are disclosed, and (c) the context in which chronic structural stressors are disclosed and the content of these disclosures.Results77% of adolescents disclosed at least one chronic structural stressor and that the presence of stressors exacerbated psychological distress, reduced treatment engagement, and decreased perceptions of intervention effectiveness.ConclusionsOur findings suggest that there is a missed opportunity to improve the effectiveness of treatment for PTSD by incorporating intervention elements that directly target structural stressors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR

PurposeStigma is a fundamental driver of HIV disparities among transgender women (TW). The gender minority stress and resilience (GMSR) measure has not been validated in Spanish-speaking, resource-limited settings. We examined the psychometric properties of a translated and abbreviated GMSR among TW in Tijuana, Mexico.MethodsFrom 2020 to 2021, 152 participants were recruited through social media and venue-based sampling. We collected information on the abbreviated GMSR, psychosocial factors (e.g., depressive symptoms), and sociodemographics. The abbreviated GMSR assessed 7 factors (Discrimination, Rejection, Internalized Transphobia, Negative Expectations, Nondisclosure, Pride, and Community Connectedness). Confirmatory factor analysis, Cronbach's alphas, and McDonald's omegas assessed structural validity. Pearson's partial correlations assessed criterion, convergent, and discriminant validities.ResultsThe 7-factor structure solution had acceptable fit (root mean square error of approximation [95% confidence interval]=0.05 [0.05-0.06]; comparative fit index/Tucker-Lewis index=0.92/0.91); and internal reliability (α=0.62-0.89; ω=0.62-0.89). Depressive (r=0.22-0.43; p

BackgroundScalable PTSD screening strategies must be brief, accurate and capable of administration by a non-specialized workforce.MethodsWe used PTSD as determined by the structured clinical interview as our gold standard and considered predictors sets of (a) Posttraumatic Stress Checklist-5 (PCL-5), (b) Primary Care PTSD Screen for the DSM-5 (PC-PTSD) and, (c) PCL-5 and PC-PTSD questions to identify the optimal items for PTSD screening for public sector settings in Kenya. A logistic regression model using LASSO was fit by minimizing the average squared error in the validation data. Area under the receiver operating characteristic curve (AUROC) measured discrimination performance.ResultsPenalized regression analysis suggested a screening tool that sums the Likert scale values of two PCL-5 questions-intrusive thoughts of the stressful experience (#1) and insomnia (#21). This had an AUROC of 0.85 (using hold-out test data) for predicting PTSD as evaluated by the MINI, which outperformed the PC-PTSD. The AUROC was similar in subgroups defined by age, sex, and number of categories of trauma experienced (all AUROCs>0.83) except those with no trauma history- AUROC was 0.78.ConclusionIn some East African settings, a 2-item PTSD screening tool may outperform longer screeners and is easily scaled by a non-specialist workforce.

BackgroundTraumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are potential risk factors for the development of dementia including Alzheimer's disease (AD) in later life. The findings of studies investigating this question are inconsistent though.ObjectiveTo investigate if these inconsistencies are caused by the existence of subgroups with different vulnerability for AD pathology and if these subgroups are characterized by atypical tau load/atrophy pattern.MethodsThe MRI and PET data of 89 subjects with or without previous TBI and/or PTSD from the DoD ADNI database were used to calculate an age-corrected gray matter tau mismatch metric (ageN-T mismatch-score and matrix) for each subject. This metric provides a measure to what degree regional tau accumulation drives regional gray matter atrophy (matrix) and can be used to calculate a summary score (score) reflecting the severity of AD pathology in an individual.ResultsThe ageN-T mismatch summary score was positively correlated with whole brain beta-amyloid load and general cognitive function but not with PTSD or TBI severity. Hierarchical cluster analysis identified five different spatial patterns of tau-gray matter interactions. These clusters reflected the different stages of the typical AD tau progression pattern. None was exclusively associated with PTSD and/or TBI.ConclusionsThese findings suggest that a) although subsets of patients with PTSD and/or TBI develop AD-pathology, a history of TBI or PTSD alone or both is not associated with a significantly higher risk to develop AD pathology in later life. b) remote TBI or PTSD do not modify the typical AD pathology distribution pattern.

This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). Changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score (primary endpoint) and Sheehan Disability Scale (SDS) functional impairment score (key secondary endpoint) were assessed by blinded independent assessors. Participants were randomized to MDMA-AT (n = 53) or placebo with therapy (n = 51). Overall, 26.9% (28/104) of participants had moderate PTSD, and 73.1% (76/104) of participants had severe PTSD. Participants were ethnoracially diverse: 28 of 104 (26.9%) identified as Hispanic/Latino, and 35 of 104 (33.7%) identified as other than White. Least squares (LS) mean change in CAPS-5 score (95% confidence interval (CI)) was -23.7 (-26.94, -20.44) for MDMA-AT versus -14.8 (-18.28, -11.28) for placebo with therapy (P

Premature dropout from posttraumatic stress disorder treatment (PTSD) hinders treatment response. Studies have primarily used quantitative methodology to identify factors that contribute to Veterans' premature dropout, which has yielded mixed results. Qualitative methods provide rich data and generate additional hypotheses about why Veterans discontinue PTSD treatment. This study aimed to understand Veterans' reasons for dropping out of prolonged exposure therapy (PE) and to examine if there are differences in reasons for dropout between three delivery modalities: in-home, in-person (IHIP), office-based telehealth (OBT), or home-based telehealth (HBT). Twenty-two Veterans who dropped out of PE from a parent randomized clinical trial participated in individual qualitative interviews about potential contextual and individual factors related to discontinuation. Team-based coding was used to conduct open and focused coding. Themes were generated that described factors that influenced Veterans' dropout from PE and constant comparison was used to explore differences in reasons between the three modalities. Most Veterans had multiple reasons for dropping out and reasons were similar across delivery modalities with few differences. Practical barriers (e.g., scheduling difficulties), attitudes toward mental health providers and therapy (e.g., stigma), psychological and physical health factors (e.g., perceived worsening of symptoms, pain), and the therapeutic context (e.g., disliking aspects of PE) contributed to Veterans' decisions to drop out from PE. Veterans in OBT reported more types of practical barriers than Veterans in HBT and IHIP. These findings can help generate hypotheses about interventions that may promote engagement and future studies should continue to study how to reduce dropout. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

IntroductionAlcohol use disorder (AUD) and PTSD have high rates of co-occurrence in U.S. Military Veterans resulting in incrementally worse functional outcomes relative to having either one of these disorders alone. Cognitive dysfunction can impede one's ability to benefit from standard behavioral AUD and PTSD treatments. Cigarette smoking is also highly prevalent among U.S. Military Veterans, and cognitive dysfunction is associated with chronic cigarette use among individuals with AUD and PTSD independently. However, much less is known about to what extent cigarette smoking further impairs cognitive functioning in individuals with both co-occurring AUD and PTSD.Materials and methodsU.S. Veterans with co-occurring AUD and PTSD (n = 162) completed a comprehensive cognitive assessment covering various domains: working memory, processing speed, mental switching, cognitive inhibition, auditory-verbal learning, auditory-verbal memory, and verbal fluency. To examine the impact of alcohol use, traumatic stress, and cigarette smoking on cognitive function, we conducted a three-way interaction examining the moderated effects of smoking status on the association between alcohol use and PTSD symptoms on a composite domain of global cognition.ResultsSmoking status in Veterans with co-occurring AUD and PTSD moderated the relationship between alcohol use and global cognition (P = .042), such that higher levels of alcohol use in the past week were related to worse global cognitive function among Veterans cigarette smokers (P = .015) but not among nonsmokers (P = .833). On follow-up analyses of individual cognitive domains, greater alcohol use in the past week was associated with lower cognitive inhibition in smokers but not nonsmokers, with traumatic stress symptoms moderating this effect (P = .039). Additionally, smoking status moderated the relationship between alcohol use and auditory-verbal learning, such that there was a differential relationship between alcohol use and auditory-verbal learning between smokers and nonsmokers.ConclusionsOverall, results provide evidence for the compounding impact of alcohol use, traumatic stress, and cigarette smoking on cognitive functioning. Impaired cognitive performance on a global level as well as on individual domains of cognitive inhibition and auditory-verbal learning were evident. Cognitive dysfunction may impede a Veteran's ability to benefit from therapeutic treatment, and these cognitive domains may represent potential targets for cognitive training efforts. Further, study results support smoking cessation initiatives and smoke-free policies enacted at Veterans Affairs healthcare facilities and medical centers.

BackgroundDespite programs to address housing for Veterans, they continue to be at high risk of unstable housing. Interpersonal violence is also highly prevalent among Veterans and may contribute to unstable housing. Our study aimed to determine whether interpersonal violence was associated with unstable housing among Veterans, and how this association was influenced by common co-occurring conditions such as substance use and mental illness.MethodsVeterans in the Mind Your Heart Study (N = 741) completed survey data on history of interpersonal violence and access to housing in the prior year. Interpersonal violence was defined as experiencing sexual violence, physical violence, or mugging/physical attack using the Brief Trauma Questionnaire. Multivariable models examined associations between interpersonal violence and unstable housing. Primary models were adjusted for age and sex. Potential explanatory factors were added in subsequent models, including marital status, education, income, substance use disorder, PTSD, and other mental illness.ResultsVeterans who had experienced interpersonal violence had almost twice the odds of unstable housing after adjustment for age and sex (AOR 1.9, 95% CI 1.2-3.0). This association was attenuated in the fully adjusted model including substance use, PTSD, and other mental illness, illustrating the interdependence of these factors (AOR 1.5, 95% CI 0.91-2.5). Subtypes of interpersonal violence were individually associated with increased odds of unstable housing after adjustment for age and sex (physical abuse AOR 1.7, 95% CI 1.2-2.5; mugging/physical attack AOR 1.8, 95% CI 1.2-2.7; sexual violence AOR 1.4, 95% CI 0.89-2.2), but were no longer significant in the fully adjusted model.ConclusionsPrevious experiences of interpersonal violence were associated with unstable housing among Veterans. Substance use, PTSD, and other mental illness played an important role in this relationship-highlighting the potential to improve health outcomes through trauma informed approaches that address mental health, substance use, and housing concurrently.

BackgroundPosttraumatic stress disorder (PTSD) symptoms can develop following acute, life-threatening medical events. This study explores a potential biomarker of PTSD risk that is novel to a medical trauma population: a noninvasive, mobile skin conductance (SC) measurement.MethodsParticipants (N=64) were enrolled in-hospital following a stroke or transient ischemic attack (TIA). Mobile measurement of SC reactivity to recalling the stroke/TIA traumatic event was conducted at hospital bedside in the days following the stroke/TIA. PTSD symptoms that developed in response to the stroke/TIA were measured at 1-month follow-up. We tested the association between SC reactivity and total 1-month PTSD symptoms, as well as PTSD symptom dimensions of fear and dysphoria.ResultsIn unadjusted analyses, there were significant positive associations between in-hospital SC reactivity to recalling the stroke/TIA traumatic event and higher-order fear-related symptoms (r=.30, p=.016), as well as lower-order fear-related symptoms of anxious arousal (r=.27, p=.035) and avoidance (r=.25, p=.043) at 1 month. Associations between SC reactivity and the fear, anxious arousal, and avoidance symptom dimensions remained significant in multivariable regression models that adjusted for relevant covariates including age, gender, stroke severity, medical comorbidity, and psychosocial factors. Although there was a positive association observed between SC reactivity to recalling the stroke/TIA event and total PTSD symptom severity at 1-month follow-up, it did not reach the level of statistical significance (r=.23, p=.070). Further, no significant association was detected for dysphoria-related symptoms (r=.11, p=.393).ConclusionsThis is the first study to test the prospective association of SC reactivity with PTSD symptom development following a medical trauma. The findings indicate that mobile measures of SC reactivity may be useful for in-hospital identification of individuals at risk for fear-related PTSD symptom development following a medical event and highlight the potential mechanisms involved in the development of these symptoms following a medical event.

BackgroundPosttraumatic stress disorder (PTSD) is common in primary care patients; however, evidence-based treatments are typically only available in specialty mental healthcare settings and often not accessed.ObjectiveTo test the effectiveness of a brief primary care-based treatment, Clinician-Supported PTSD Coach (CS PTSD Coach) was compared with Primary Care Mental Health Integration-Treatment as Usual (PCMHI-TAU) in (1) reducing PTSD severity, (2) engaging veterans in specialty mental health care, and (3) patient satisfaction with care.DesignMulti-site randomized pragmatic clinical trial.ParticipantsA total of 234 veterans with PTSD symptoms who were not currently accessing PTSD treatment.InterventionCS PTSD Coach was designed to be implemented in Veterans Affairs PCMHI and combines mental health clinician support with the "PTSD Coach" mobile app. Four 30-min sessions encourage daily use of symptom management strategies.Main measuresPTSD severity was measured by clinician-rated interviews pre- and post-treatment (8 weeks). Self-report measures assessed PTSD, depression, and quality of life at pretreatment, posttreatment, and 16- and 24-week follow-ups, and patient satisfaction at post-treatment. Mental healthcare utilization was extracted from medical records.Key resultsClinician-rated PTSD severity did not differ by condition at post-treatment. CS PTSD Coach participants improved more on patient-reported PTSD severity at post-treatment than TAU participants (D = .28, p = .021). Coach participants who continued to have problematic PTSD symptoms at post-treatment were not more likely to engage in 2 sessions of specialty mental health treatment than TAU participants. Coach participants engaged in 74% more sessions in the intervention and reported higher treatment satisfaction than TAU participants (p

ObjectiveThis study is a non-randomized pragmatic trial to assess the feasibility and acceptability of the Primary Care Intervention for Posttraumatic stress disorder (PCIP) (Srivastava et al., 2021), an Integrated Behavioral Health Care treatment for PTSD in adolescents.MethodFollowing routine clinic procedures, youth who were suspected of having trauma-related mental health symptoms were referred by their primary care providers to integrated care social workers for evaluation. The integrated care social workers referred the first 23 youth whom they suspected of having PTSD to the research study. Twenty youth consented to the study and 19 completed the pre-assessment (17 female; mean age = 19.32, SD = 2.11; range 14-22 years). More than 40% identified as Black and a third as Hispanic/Latinx. PCIP mechanisms and clinical outcomes were assessed pre- and post-treatment, and at one-month follow-up. Participants and therapists completed post-treatment qualitative interviews to assess feasibility and acceptability, and treatment sessions were audio recorded to assess fidelity.ResultsFindings suggest high acceptability, satisfaction, and feasibility of the PCIP delivered in "real-life" safety net pediatric primary care. Integrated care social workers had high treatment fidelity. Despite the small sample size, there was significant improvement in symptom scores of anxiety (g = 0.68, p = 0.02) and substance use (g = 0.36, p = 0.04) from pre to post, and depression symptoms (g = 0.38, p = 0.04) from pre to follow-up. Qualitative data from patients who completed exit interviews and integrated social workers indicated high satisfaction with the treatment, with some participants reporting that the integrated intervention was more acceptable and less stigmatizing than seeking mental health care outside of primary care.ConclusionsThe PCIP may improve treatment engagement and access for vulnerable youth. Promising findings of high acceptability, feasibility, and initial clinical effectiveness suggest that PCIP warrants larger-scale study as part of routine care in pediatric integrated care.

BackgroundSocial support is associated with decreased symptoms of postpartum mood and anxiety disorders (PMAD) in mothers of healthy infants, but less is known about social support and PMADs in mothers with preterm infants. The purpose of this study was to examine the relationship between social support and symptoms of PMADs reported by mothers in the months following hospital discharge of their preterm infant.MethodsMothers of infants less than 33 weeks gestational age were enrolled from neonatal intensive care units (NICU) at 6 sites. Mothers completed PMAD measures of depression, anxiety and post-traumatic stress approximately 3 months following their infant's discharge. Multivariable regression was used to evaluate relationships between social support and PMAD measures.ResultsOf 129 mothers, 1 in 5 reported clinically significant PMAD symptoms of: depression (24%), anxiety (19%), and post-traumatic stress (20%). Social support was strongly inversely associated with all 3 PMADs. Social support explained between 21% and 26% of the variance in depression, anxiety and post-traumatic stress symptoms.ConclusionIncreased social support may buffer PMAD symptoms in mothers of preterm infants after discharge. Research is needed to determine effective screening and interventions aimed at promoting social support for all parents during and following their infant's hospitalisation.

Purpose of reviewTreatment for musculoskeletal sports injuries often neglects the psychological components of health and recovery. Pediatric patients require particular consideration of their psychosocial and cognitive development. This systematic review investigates the effects of musculoskeletal injury on mental health in pediatric athletes.Recent findingsAthlete identity may increase in adolescence and is associated with worse mental health post-injury. Psychological models suggest loss of identity, uncertainty, and fear mediate the association between injury and symptoms of anxiety, depression, post-traumatic stress disorder, and obsessive-compulsive disorder. Fear, identity, and uncertainty also influence return to sport. In the reviewed literature, there were 19 psychological screening tools and 8 different physical health measures with various adaptations to athlete developmental level. In pediatric patients, no interventions were studied to reduce the psychosocial impacts of injury. Musculoskeletal injury is associated with worse mental health in pediatric athletes, and stronger athlete identity is a risk factor for the development of depressive symptoms. Psychological interventions that reduce uncertainty and address fear may help mitigate these risks. More research is needed on screening and interventions to improve mental health post-injury.

The notion of "biological aging" as distinct from chronological aging has been of increasing interest in psychiatry, and many studies have explored associations of stress and psychiatric illness with accelerated biological aging. The "epigenetic clocks" are one avenue of this research, wherein "biological age" is estimated using DNA methylation data from specific CpG dinucleotide sites within the human genome. Many iterations of the epigenetic clocks have been developed, but the GrimAge clock continues to stand out for its ability to predict morbidity and mortality. Several studies have now explored associations of stress, PTSD, and MDD with GrimAge acceleration (GrimAA). While stress, PTSD, and MDD are distinct psychiatric entities, they may share common mechanisms underlying accelerated biological aging. Yet, no one has offered a review of the evidence on associations of stress and stress-related psychopathology with GrimAA. In this review, we identify nine publications on associations of stress, PTSD, and MDD with GrimAA. We find that results are mixed both within and across each of these exposures. However, we also find that analytic methods - and specifically, the choice of covariates - vary widely between studies. To address this, we draw upon popular methods from the field of clinical epidemiology to offer (1) a systematic framework for covariate selection, and (2) an approach to results reporting that facilitates analytic consensus. Although covariate selection will differ by the research question, we encourage researchers to consider adjustment for tobacco, alcohol use, physical activity, race, sex, adult socioeconomic status, medical comorbidity, and blood cell composition.

The neurophysiological mechanisms in the human amygdala that underlie post-traumatic stress disorder (PTSD) remain poorly understood. In a first-of-its-kind pilot study, we recorded intracranial electroencephalographic data longitudinally (over one year) in two male individuals with amygdala electrodes implanted for the management of treatment-resistant PTSD (TR-PTSD) under clinical trial NCT04152993. To determine electrophysiological signatures related to emotionally aversive and clinically relevant states (trial primary endpoint), we characterized neural activity during unpleasant portions of three separate paradigms (negative emotional image viewing, listening to recordings of participant-specific trauma-related memories, and at-home-periods of symptom exacerbation). We found selective increases in amygdala theta (5-9 Hz) bandpower across all three negative experiences. Subsequent use of elevations in low-frequency amygdala bandpower as a trigger for closed-loop neuromodulation led to significant reductions in TR-PTSD symptoms (trial secondary endpoint) following one year of treatment as well as reductions in aversive-related amygdala theta activity. Altogether, our findings provide early evidence that elevated amygdala theta activity across a range of negative-related behavioral states may be a promising target for future closed-loop neuromodulation therapies in PTSD.

Post-traumatic stress disorder (PTSD) is a multisystem syndrome. Integration of systems-level multi-modal datasets can provide a molecular understanding of PTSD. Proteomic, metabolomic, and epigenomic assays are conducted on blood samples of two cohorts of well-characterized PTSD cases and controls: 340 veterans and 180 active-duty soldiers. All participants had been deployed to Iraq and/or Afghanistan and exposed to military-service-related criterion A trauma. Molecular signatures are identified from a discovery cohort of 218 veterans (109/109 PTSD+/-). Identified molecular signatures are tested in 122 separate veterans (62/60 PTSD+/-) and in 180 active-duty soldiers (PTSD+/-). Molecular profiles are computationally integrated with upstream regulators (genetic/methylation/microRNAs) and functional units (mRNAs/proteins/metabolites). Reproducible molecular features of PTSD are identified, including activated inflammation, oxidative stress, metabolic dysregulation, and impaired angiogenesis. These processes may play a role in psychiatric and physical comorbidities, including impaired repair/wound healing mechanisms and cardiovascular, metabolic, and psychiatric diseases.

BackgroundDysfunction in major stress response systems during the acute aftermath of trauma may contribute to risk for developing posttraumatic stress disorder (PTSD). The current study investigated how PTSD diagnosis and symptom severity, depressive symptoms, and childhood trauma uniquely relate to diurnal neuroendocrine secretion (cortisol and alpha-amylase rhythms) in women who recently experienced interpersonal trauma compared to non-traumatized controls (NTCs).MethodUsing a longitudinal design, we examined diurnal cortisol and alpha-amylase rhythms in 98 young women (n = 57 exposed to recent interpersonal trauma, n = 41 NTCs). Participants provided saliva samples and completed symptom measures at baseline and 1-, 3-, and 6-month follow-up.ResultsMultilevel models (MLMs) revealed lower waking cortisol predicted the development of PTSD in trauma survivors and distinguished at-risk women from NTCs. Women with greater childhood trauma exposure exhibited flatter diurnal cortisol slopes. Among trauma-exposed individuals, lower waking cortisol levels were associated with higher concurrent PTSD symptom severity. Regarding alpha-amylase, MLMs revealed women with greater childhood trauma exposure exhibited higher waking alpha-amylase and slower diurnal alpha-amylase increase.ConclusionsResults suggest lower waking cortisol in the acute aftermath of trauma may be implicated in PTSD onset and maintenance. Findings also suggest childhood trauma may predict a different pattern of dysfunction in stress response systems following subsequent trauma exposure than the stress system dynamics associated with PTSD risk; childhood trauma appears to be associated with flattened diurnal cortisol and alpha-amylase slopes, as well as higher waking alpha-amylase.

This multi-method study examined perspectives on mindfulness and coping strategies used by trauma-exposed women experiencing homelessness (WEH), residing in a state-funded residential drug treatment site in Southern California (United States). Questionnaires and in-depth focus group interviews were utilised to examine traumatic experiences over the lifespan, probable-posttraumatic stress disorder (PTSD), and coping strategies. Mindfulness was explored as a potential way to improve coping; potential benefits and challenges associated with implementing a mindfulness-based intervention (MBI) with trauma-exposed WEH were also investigated. A Community Advisory Board (CAB) was formed to identify key issues experienced by WEH and to develop a semi structured interview guide (SSIG). Using the SSIG, women participated in one of four focus groups (total N = 28; n = 7 per group). Quantitative data on demographic indicators, probable-PTSD, and trauma exposure were collected. Almost 90% of women met criteria for probable-PTSD; trauma exposure was exceedingly high; most women had experienced multiple traumas throughout their lives. Four main themes emerged from qualitative analyses, which drew from Grounded Theory and used open, selective, and axial coding: (1) ways of coping with trauma; (2) perspectives on mindfulness; (3) prior experiences with mindfulness; and (4) challenges for conducting a mindfulness programme. Overall, WEH used a variety of coping techniques to deal with their trauma, had some familiarity with mindfulness, and were optimistic an MBI would be helpful, despite identifying several challenges to implementation. MBIs may be helpful adjuncts to traditional care for trauma-exposed, WEH, recovering from substance use disorder. Population-specific considerations may improve implementation and participation.

Trauma-informed beliefs often decrease during posttraumatic stress disorder (PTSD) treatment. This may also extend to anxiety sensitivity (AS), defined as a fear of anxiety-related sensations and beliefs that anxiety is dangerous and/or intolerable. However, little is known about how AS changes during exposure-based and psychopharmacological PTSD treatments. Further, high AS may be a risk factor for diminished PTSD symptom improvement and increased treatment dropout. To better understand how AS impacts and is impacted by PTSD treatment, we conducted a secondary analysis of a randomized clinical trial with a sample of 223 veterans (87.0% male, 57.5% White) with PTSD from four U.S. sites. Veterans were randomized to receive prolonged exposure (PE) plus placebo (n = 74), sertraline plus enhanced medication management (n = 74), or PE plus sertraline (n = 75). Veterans answered questions about PTSD symptoms and AS at baseline and 6-, 12-, 24-, 36-, and 52-week follow-ups. High baseline AS was related to high levels of PTSD severity at 24 weeks across all conditions, β = .244, p = .013, but did not predict dropout from exposure-based, β = .077, p = .374, or psychopharmacological therapy, β = .009, p = .893. AS also significantly decreased across all three treatment arms, with no between-group differences; these reductions were maintained at the 52-week follow-up. These findings suggest that high AS is a risk factor for attenuated PTSD treatment response but also provide evidence that AS can be improved by both PE and an enhanced psychopharmacological intervention for PTSD.

Oxytocin (OT) is involved in the regulation of physiological processes and emotional states, with increasing evidence for its beneficial actions being mediated by the autonomic and immune systems. Growing evidence suggests that OT plays a role in the pathophysiology of different psychiatric disorders. Given the limited information in humans the aim of this study was to retrospectively explore plasma OT levels in psychiatric patients, particularly focusing on sex-related differences, as compared with healthy controls. The patients studied here were divided into three groups diagnosed with obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD) or major depressive disorder (MDD). Plasma OT levels were significantly different between healthy men and women, with the latter showing higher values, while none of the three psychiatric groups showed sex-related differences in the parameters measured here. The intergroup analyses showed that the OT levels were significantly higher in OCD, lower in PTSD and even more reduced in MDD patients than in healthy subjects. These differences were also confirmed when gender was considered, with the exception of PTSD men, in whom OT levels were similar to those of healthy men. The present results indicated that OT levels were higher amongst healthy women than men, while a sex difference was less apparent or reversed in psychiatric patients. Reductions in sex differences in psychopathologies may be related to differential vulnerabilities in processes associated with basic adaptive and social functions.

Trauma exposure and post-traumatic stress disorder (PTSD) impact emotional and physical well-being, social functioning, and parent-child relationship quality. The effect of parental trauma on parenting and child maltreatment is often overlooked by current child welfare (CW) services. The novel intervention, Parenting-STAIR, was created to address maternal mental health, parenting skills, and child well-being outcomes. Parenting-STAIR is a combination of Skills Training in Affective and Interpersonal Regulation (STAIR) Narrative Therapy and Parent-Child Care (PC-CARE). This open pilot study aimed to examine the feasibility and preliminary impact of Parenting-STAIR in reducing maternal PTSD and increasing positive parenting skills for mothers and families involved in the child welfare system. Parenting-STAIR was delivered to 111 mothers receiving family preservation services in New York City. Of these, 70 completed treatment; statistical and clinically significant changes were observed for maternal PTSD and depression as well as in parenting stress, parenting skills, and child behaviors. These findings provide encouraging initial evidence for the feasibility and impact of this novel PTSD intervention. An evaluation of maltreatment recidivism is needed, as well as implementation of a randomized controlled trial to establish efficacy of the intervention.

BackgroundThe coronavirus disease-2019 (COVID-19) pandemic has caused myriad health, social, and economic stressors. To date, however, no known study has examined changes in mental health during the pandemic in the U.S. military veteran population.MethodsData were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, a nationally representative, prospective cohort survey of 3078 veterans. Pre-to-peri-pandemic changes in psychiatric symptoms were evaluated, as well as pre-pandemic risk and protective factors and pandemic-related correlates of increased psychiatric distress.ResultsThe prevalence of generalized anxiety disorder (GAD) positive screens increased from pre- to peri-pandemic (7.1% to 9.4%; p < 0.001) and was driven by an increase among veterans aged 45-64 years (8.2% to 13.5%; p < 0.001), but the prevalence of major depressive disorder and posttraumatic stress disorder positive screens remained stable. Using a continuous measure of psychiatric distress, an estimated 13.2% of veterans reported a clinically meaningful pre-to-peri-pandemic increase in distress (mean = 1.1 standard deviation). Veterans with a larger pre-pandemic social network size and secure attachment style were less likely to experience increased distress, whereas veterans reporting more pre-pandemic loneliness were more likely to experience increased distress. Concerns about pandemic-related social losses, mental health COVID-19 effects, and housing stability during the pandemic were associated with increased distress, over-and-above pre-pandemic factors.ConclusionsAlthough most U.S. veterans showed resilience to mental health problems nearly 1 year into the pandemic, the prevalence of GAD positive screens increased, particularly among middle-aged veterans, and one of seven veterans experienced increased distress. Clinical implications of these findings are discussed.

Gender-based violence (GBV) against transgender and nonbinary (TGNB) persons is a pervasive public health issue. GBV has been linked to mental health problems such as depression and posttraumatic stress disorder (PTSD), as well has risk for HIV seroconversion and HIV treatment nonadherence. However, the impact of GBV on HIV pre-exposure prophylaxis (PrEP) use among TGNB persons has yet to be investigated. In the current study we assessed longitudinal PrEP persistence data from dried blood spots (DBS) collected from 172 racially and ethnically diverse TGNB participants during a 48-week PrEP demonstration project in Southern California from June 2017 to September 2020. Participants were categorized into three levels of PrEP uptake and persistence based on their PrEP levels at the start and end of the study: low-low, high-low, and high-high. Individual-, social-, and structural-level variables were then entered into multinomial logistic regression models to predict levels of PrEP uptake and persistence based on hypotheses informed by syndemic and minority stress theories. The models demonstrated that experience of GBV predicted significantly lower odds of PrEP uptake and persistence and greater PTSD symptoms predicted significantly greater odds of early PrEP discontinuation. Higher levels of coping skills, already being on PrEP at baseline, and being in a steady relationship were associated with greater odds of PrEP uptake and persistence. Implications for future GBV research, advocacy, interventions, and much needed structural changes focused on improving the health and safety of TGNB individuals are discussed.

Post-Traumatic Stress Disorder (PTSD) is not solely a psychiatric disorder; it also includes significant medical morbidity. Although there is evidence of increased risk of metabolic syndrome (MetS) in PTSD, the interpretation of previous studies is confounded by inclusion of people on antipsychotic medications, which independently cause increased MetS. In this study we investigated whether Veterans with PTSD not treated with antipsychotic medications (n=115) demonstrate increased MetS compared to an age-comparable group of people from the U.S. National Health and Nutrition Examination Survey (NHNES; n=1005). Using standardized criteria (abnormal values in 3 out of the 5 domains of obesity, hypertension, high density lipoprotein, triglyceride and fasting glucose concentrations) we compared the prevalence of MetS across groups. Relative to the NHNES group, a significantly higher proportion of the Veteran PTSD group met criteria for MetS (26.9% vs. 41.7%) with a higher proportion of abnormal values in four out of five MetS domains (excepting glucose). Our results suggest that the elevation of MetS associated with PTSD cannot be fully explained by iatrogenic effects of antipsychotic medication. We suggest that extra attention be devoted to the clinical management of metabolic risk factors for morbidity in patients with PTSD.

BackgroundPosttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid and are associated with significant functional impairment and inconsistent treatment outcomes. Data-driven subtyping of this clinically heterogeneous patient population and the associated underlying neural mechanisms are highly needed to identify who will benefit from psychotherapy.MethodsIn 53 comorbid PTSD/AUD patients, resting-state functional magnetic resonance imaging was collected prior to undergoing individual psychotherapy. We used a data-driven approach to subgroup patients based on directed connectivity profiles. Connectivity subgroups were compared on clinical measures of PTSD severity and heavy alcohol use collected at pre- and post-treatment.ResultsWe identified a subgroup of patients associated with improvement in PTSD symptoms from integrated-prolonged exposure therapy. This subgroup was characterized by lower insula to inferior parietal cortex (IPC) connectivity, higher pregenual anterior cingulate cortex (pgACC) to posterior midcingulate cortex connectivity and a unique pgACC to IPC path. We did not observe any connectivity subgroup that uniquely benefited from integrated-coping skills or subgroups associated with change in alcohol consumption.ConclusionsData-driven approaches to characterize PTSD/AUD subtypes have the potential to identify brain network profiles that are implicated in the benefit from psychological interventions - setting the stage for future research that targets these brain circuit communication patterns to boost treatment efficacy.

BackgroundVeterans with post-traumatic stress disorder (PTSD) are more likely to report chronic pain than veterans without PTSD. Yoga has been shown to reduce both chronic pain and PTSD symptoms in clinical trials. The goal of our study was to assess the feasibility and acceptability of conducting a randomized controlled trial (RCT) that combined yoga and mantram repetition (Yoga + MR) into one program for military veterans with both chronic pain and PTSD.MethodsIn this feasibility RCT, 27 veterans were randomized to either Yoga + MR or a relaxation intervention. Due to the COVID-19 pandemic, in-person recruitment, assessments, and intervention attendance were re-evaluated. Although remote delivery of aspects of the study were utilized, interventions were delivered in-person. Feasibility benchmarks met included full recruitment in 12 months or less, 75%+ retention at initial follow-up assessment, 50%+ attendance rate, and 75%+ of participants satisfied with the interventions.ResultsThe sample was racially and ethnically diverse, and 15% of participants were women. Participant recruitment lasted approximately 11 months. Out of 32 participants initially randomized, two participants asked to be dropped from the study and three did not meet PTSD symptom criteria. For the remaining 27 participants, retention rates were 85% at 12 weeks and 81% at 18 weeks. Participants attended 66% of in-person yoga and 55% of in-person relaxation sessions. Satisfaction was high, with 100% of yoga participants and 75%/88% of relaxation participants agreeing or strongly agreeing they were satisfied with the intervention/instructors. After 12 weeks (end of intervention), Yoga + MR participants reported reduced back-pain related disability (primary outcome), reduced alcohol use, reduced fatigue, and increased quality of life, while relaxation group participants reported reductions in pain severity, PTSD symptoms, and fatigue.ConclusionsAmidst many research challenges during the pandemic, recruitment, retention, and efficacy results from this feasibility trial support advancement to a larger RCT to study Yoga + MR for chronic pain and PTSD.

INTRODUCTION: Traumatic brain injury (TBI) is one of the highest public health priorities, especially among military personnel where comorbidity with post-traumatic stress symptoms and resulting consequences is high. Brain injury and post-traumatic stress symptoms are both characterized by dysfunctional brain networks, with the amygdala specifically implicated as a region with both structural and functional abnormalities. METHODS: This study examined the structural volumetrics and resting state functional connectivity of 68 Active Duty Service Members with or without chronic mild TBI (mTBI) and comorbid symptoms of Post-Traumatic Stress (PTS). RESULTS AND DISCUSSION: Structural analysis of the amygdala revealed no significant differences in volume between mTBI and healthy comparison participants with and without post-traumatic stress symptoms. Resting state functional connectivity with bilateral amygdala revealed decreased anterior network connectivity and increased posterior network connectivity in the mTBI group compared to the healthy comparison group. Within the mTBI group, there were significant regions of correlation with amygdala that were modulated by PTS severity, including networks implicated in emotional processing and executive functioning. An examination of a priori regions of amygdala connectivity in the default mode network, task positive network, and subcortical structures showed interacting influences of TBI and PTS, only between right amygdala and right putamen. These results suggest that mTBI and PTS are associated with hypo-frontal and hyper-posterior amygdala connectivity. Additionally, comorbidity of these conditions appears to compound these neural activity patterns. PTS in mTBI may change neural resource recruitment for information processing between the amygdala and other brain regions and networks, not only during emotional processing, but also at rest.

Mild Traumatic Brain Injury (mTBI, or concussion) is a debilitating condition that often leads to persistent cognitive and mental health problems post-injury. Post-traumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD) are two most commonly occurring mental health problems following mTBI and are suggested to be strong contributors to the persistent post-concussion symptoms. Thus, it is important to understand the symptomatology of PTSD and MDD post-mTBI, to better inform targets for behavioral health interventions. Therefore, the current study examined the symptom structure of post-mTBI co-morbid PTSD and MDD through network approaches; we compared the network structure of participants with a positive mTBI screen (N = 753) to the network structure of participants with a negative mTBI screen (N = 2044); lastly, we examined a network of PTSD and MDD symptoms with clinical covariates in a positive mTBI sample. We found that feeling distant/cutoff (P10) and difficulty concentrating (P15) were the most central symptoms in the positive mTBI network and sleep problems were the most prominent bridge nodes across the disorders. No significant difference between the positive and negative mTBI network were found through network comparison tests. Moreover, anxiety and insomnia were strongly associated with sleep symptoms and irritability symptoms, and emotional support and resilience were potential buffers against most of the PTSD and MDD symptoms. The results of this study might be particularly useful for identifying targets (i.e., feeling distant, concentration and sleep problems) for screening, monitoring and treatment after concussion to better inform post-mTBI mental health care and to improve treatment outcomes.

Many patients with mild traumatic brain injury (mTBI) are at risk for mental health problems such as posttraumatic stress disorder (PTSD). The objective of this study was to determine whether the polygenic risk for PTSD (or for related mental health disorders or traits including major depressive disorder [MDD] and neuroticism [NEU]) was associated with an increased likelihood of PTSD in the aftermath of mTBI. We used data from individuals of European ancestry with mTBI enrolled in TRACK-TBI (n = 714), a prospective longitudinal study of level 1 trauma center patients. One hundred and sixteen mTBI patients (16.3%) had probable PTSD (PCL-5 score ≥33) at 6 months post-injury. We used summary statistics from recent GWAS studies of PTSD, MDD, and NEU to generate polygenic risk scores (PRS) for individuals in our sample. A multivariable model that included age, sex, pre-injury history of mental disorder, and cause of injury explained 7% of the variance in the PTSD outcome; the addition of the PTSD-PRS (and five ancestral principal components) significantly increased the variance explained to 11%. The adjusted odds of PTSD in the uppermost PTSD-PRS quintile was nearly four times higher (aOR = 3.71, 95% CI 1.80-7.65) than in the lowest PTSD-PRS quintile. There was no evidence of a statistically significant interaction between PTSD-PRS and prior history of mental disorder, indicating that PTSD-PRS had similar predictive utility among those with and without pre-injury psychiatric illness. When added to the model, neither MDD-PRS nor NEU-PRS were significantly associated with the PTSD outcome. These findings show that the risk for PTSD in the context of mTBI is, in part, genetically influenced. They also raise the possibility that an individual's PRS could be clinically actionable if used-possibly with other non-genetic predictors-to signal the need for enhanced follow-up and early intervention; this precision medicine approach needs to be prospectively studied.

BackgroundDespite significant research done on youth experiencing homelessness, few studies have examined movement patterns and digital habits in this population. Examining these digital behaviors may provide useful data to design new digital health intervention models for youth experiencing homelessness. Specifically, passive data collection (data collected without extra steps for a user) may provide insights into lived experience and user needs without putting an additional burden on youth experiencing homelessness to inform digital health intervention design.ObjectiveThe objective of this study was to explore patterns of mobile phone Wi-Fi usage and GPS location movement among youth experiencing homelessness. Additionally, we further examined the relationship between usage and location as correlated with depression and posttraumatic stress disorder (PTSD) symptoms.MethodsA total of 35 adolescent and young adult participants were recruited from the general community of youth experiencing homelessness for a mobile intervention study that included installing a sensor data acquisition app (Purple Robot) for up to 6 months. Of these participants, 19 had sufficient passive data to conduct analyses. At baseline, participants completed self-reported measures for depression (Patient Health Questionnaire-9 [PHQ-9]) and PTSD (PTSD Checklist for DSM-5 [PCL-5]). Behavioral features were developed and extracted from phone location and usage data.ResultsAlmost all participants (18/19, 95%) used private networks for most of their noncellular connectivity. Greater Wi-Fi usage was associated with a higher PCL-5 score (P=.006). Greater location entropy, representing the amount of variability in time spent across identified clusters, was also associated with higher severity in both PCL-5 (P=.007) and PHQ-9 (P=.045) scores.ConclusionsLocation and Wi-Fi usage both demonstrated associations with PTSD symptoms, while only location was associated with depression symptom severity. While further research needs to be conducted to establish the consistency of these findings, they suggest that the digital patterns of youth experiencing homelessness offer insights that could be used to tailor digital interventions.

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, and experiences of psychological trauma have been associated with subsequent CVD onset. Identifying key pathways connecting trauma with CVD has the potential to inform more targeted screening and intervention efforts to offset elevated cardiovascular risk. In this narrative review, we summarize the evidence for key psychological and biological mechanisms linking experiences of trauma with CVD risk. Additionally, we describe various methodologies for measuring these mechanisms in an effort to inform future research related to potential pathways. With regard to mechanisms involving posttraumatic psychopathology, the vast majority of research on psychological distress after trauma and CVD has focused on posttraumatic stress disorder (PTSD), even though posttraumatic psychopathology can manifest in other ways as well. Substantial evidence suggests that PTSD predicts the onset of a range of cardiovascular outcomes in trauma-exposed men and women, yet more research is needed to better understand posttraumatic psychopathology more comprehensively and how it may relate to CVD. Further, dysregulation of numerous biological systems may occur after trauma and in the presence of posttraumatic psychopathology; these processes of immune system dysregulation and elevated inflammation, oxidative stress, mitochondrial dysfunction, renin-angiotensin system dysregulation, and accelerated biological aging may all contribute to subsequent cardiovascular risk, although more research on these pathways in the context of traumatic stress is needed. Given that many of these mechanisms are closely intertwined, future research using a systems biology approach may prove fruitful for elucidating how processes unfold to contribute to CVD after trauma.

IntroductionApproximately half of individuals with posttraumatic stress disorder (PTSD) may meet criteria for other psychiatric disorders, and PTSD symptoms are associated with diminished health and psychosocial functioning. However, few studies examine the longitudinal progression of PTSD symptoms concurrent with related symptom domains and functional outcomes, such that may neglect important longitudinal patterns of symptom progression beyond PTSD specifically.MethodsTherefore, we used longitudinal causal discovery analysis to examine the longitudinal interrelations among PTSD symptoms, depressive symptoms, substance abuse, and various other domains of functioning in five longitudinal cohorts representing veterans (n = 241), civilians seeking treatment for anxiety disorders (n = 79), civilian women seeking treatment for post-traumatic stress and substance abuse (n = 116), active duty military members assessed 0-90 days following TBI (n = 243), and civilians with a history of TBI (n = 43).ResultsThe analyses revealed consistent, directed associations from PTSD symptoms to depressive symptoms, independent longitudinal trajectories of substance use problems, and cascading indirect relations from PTSD symptoms to social functioning through depression as well as direct relations from PTSD symptoms to TBI outcomes.DiscussionOur findings suggest PTSD symptoms primarily drive depressive symptoms over time, tend to show independence from substance use symptoms, and may cascade into impairment in other domains. The results have implications for refining conceptualization of PTSD co-morbidity and can inform prognostic and treatment hypotheses about individuals experiencing PTSD symptoms along with co-occurring distress or impairment.

BackgroundComorbid mental illness may negatively impact recovery from concussion. This study evaluated whether the level of symptom clusters at clinic intake contribute to poor mental health recovery in concussed patients during treatment, which may in turn serve as a target intervention.ObjectiveThe objective of this study is to examine the association between the level of initial symptoms and mental health symptoms among service members with concussion.MethodsData were obtained from 483 active duty service members treated in interdisciplinary treatment programs for traumatic brain injury, all of which were concussions. Pre-treatment symptom clusters included self-reported hyperarousal, dissociation/depression, cognitive dysfunction/headache and neurological symptoms. The outcomes, clinically-relevant decreases in depressive symptoms (assessed by the 8-item Patient Health Questionnaire, PHQ-8) and PTSD symptoms (assessed by the PTSD Checklist for DSM-5, PCL-5), were defined as a decrease in PHQ-8 > 5 and PCL-5 > 7, respectively. Poisson regression with robust error variance was used to evaluate the relationship between the level of each symptom cluster and clinically-relevant decrease in outcomes.ResultsParticipants with higher (vs. lower) levels of pre-treatment hyperarousal and dissociation/depression symptom cluster were less likely to improve in depressive and PTSD symptoms during treatment. The level of cognitive/headache and neurological symptom clusters were not significantly associated with any symptom changes.ConclusionThese findings support the need for individualized treatment for symptoms identified and treated after determining concussion history, with particular attention to high levels of hyperarousal and dissociation/depression prior to treatment.

BackgroundWhile evidence-based psychotherapy (EBP) for posttraumatic stress disorder (PTSD) is a first-line treatment, its real-world effectiveness is unknown. We compared cognitive processing therapy (CPT) and prolonged exposure (PE) each to an individual psychotherapy comparator group, and CPT to PE in a large national healthcare system.MethodsWe utilized effectiveness and comparative effectiveness emulated trials using retrospective cohort data from electronic medical records. Participants were veterans with PTSD initiating mental healthcare (N = 265 566). The primary outcome was PTSD symptoms measured by the PTSD Checklist (PCL) at baseline and 24-week follow-up. Emulated trials were comprised of 'person-trials,' representing 112 discrete 24-week periods of care (10/07-6/17) for each patient. Treatment group comparisons were made with generalized linear models, utilizing propensity score matching and inverse probability weights to account for confounding, selection, and non-adherence bias.ResultsThere were 636 CPT person-trials matched to 636 non-EBP person-trials. Completing ⩾8 CPT sessions was associated with a 6.4-point greater improvement on the PCL (95% CI 3.1-10.0). There were 272 PE person-trials matched to 272 non-EBP person-trials. Completing ⩾8 PE sessions was associated with a 9.7-point greater improvement on the PCL (95% CI 5.4-13.8). There were 232 PE person-trials matched to 232 CPT person-trials. Those completing ⩾8 PE sessions had slightly greater, but not statistically significant, improvement on the PCL (8.3-points; 95% CI 5.9-10.6) than those completing ⩾8 CPT sessions (7.0-points; 95% CI 5.5-8.5).ConclusionsPTSD symptom improvement was similar and modest for both EBPs. Although EBPs are helpful, research to further improve PTSD care is critical.

Abstract: Purpose: Unaccompanied immigrant children (UIC) experience significant mental health concerns, particularly posttraumatic stress. This is a vulnerable population, yet little systematic research has examined the effectiveness of evidence-based models such as cognitive behavioral therapy (CBT) to meet their needs. Integrating religious beliefs and spirituality into therapy could elucidate better understandings of traumatic stress, and posttraumatic cognitions when working with UIC with strong faith traditions/beliefs. Methods: We report on modifications made to a pre-existing treatment, consisting of integrating religious and spiritual themes, to engage and work with UIC participants in a pilot study of Mindfulness-Based CBT. Thematic analysis of therapy notes evaluated the implementation process for integrating religious and spiritual themes. Three composite vignettes illustrate how religiosity and spirituality were salient for UIC participants in this pilot study, and how these were integrated into therapy to address posttraumatic cognitions and symptoms. We assessed changes in PTSD symptom severity and posttraumatic cognitions for UIC and in comparison, to non-UIC participants using the Child PTSD Symptom Scale and the Posttraumatic Cognitions Inventory. Results: Religiosity and spirituality were important for coping and conceptualizations of trauma, served as facilitators for engaging UIC in therapy, and related to improving posttraumatic cognitions and symptoms. Conclusion: Religious identity and spirituality can be important for meaning making, trauma cognitions and symptoms, and can be important to explore in therapy with unaccompanied immigrant children and adolescents. Clinical Trial Registration: Not applicable.

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10-8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q

BackgroundChildhood adversities (CAs), potentially traumatic exposures (PTEs), and posttraumatic stress disorder (PTSD) are known to increase the risk for poor health outcomes, including diseases of aging and early mortality. Telomere length (TL) and hair cortisol concentrations (HCC) are biomarkers known to be associated with CA and PTEs, and PTSD, but there is considerable heterogeneity in findings.ObjectivesThis study aims to investigate the association of CAs, PTEs, and PTSD with TL and HCC in a high-risk sample of young adults who were previously placed in youth residential care institutions throughout Switzerland.MethodOur sample includes 130 participants (30.8% women, M Age = 26.5 ± 3.7 years) with previous youth residential care placements (MPlacements= 3.9). CAs and PTEs, as well as PTSD, were assessed with self-reported questionnaires and semi-structured clinical interviews. Immune cell TL was measured with quantitative polymerase chain reaction (qPCR) in whole blood. Hair samples were collected for HCC measurement and assayed with high-sensitivity ELISA. Multivariate regression models were fitted to describe the associations between CAs, PTEs, and PTSD with TL and HCC, adjusting for covariates.ResultsIn our high-risk sample, a higher burden of CAs, PTEs, Criterion A trauma, and PTSD was associated with longer TL. PTEs, Criterion A trauma, and PTSD were associated with lower HCC, however no significant associations between CAs and HCC were found. The magnitude of these effects varied depending on the dimensional or categorical nature of the stress-phenotype and the specific measure used.ConclusionsOur findings are in contrast with many, but not all, previous studies of associations between adversity and both TL and HCC. For instance, our findings are in line with other studies that find a state of hypocortisolism in PTSD. Better measurement of adversities and trauma, multisystem biomarker approaches, and more research in larger high-risk samples at the upper end of the adversity-continuum is warranted.

PurposeGiven data suggesting common co-occurrence and worse outcomes for individuals with eating disorders (EDs) and post-traumatic stress disorder (PTSD), it is critical to identify integrated treatment approaches for this group of patients. Past work has explored the feasibility and initial efficacy of intervention approaches that draw on evidence-based treatments for both EDs and PTSD; however, this work remains limited in scope. In the current study, we explored the feasibility and naturalistic outcomes of PTSD treatment delivered within the context of intensive ED treatment.MethodParticipants were 57 adult men and women with DSM-5 EDs and comorbid PTSD who completed a course of either Prolonged Exposure (PE; n = 22) or Cognitive Processing Therapy (CPT; n = 35) (Msessions = 10.40; SD = 5.13) and weekly validated measurements of clinical symptoms while enrolled in ED programming.ResultsMulti-level models for PTSD symptoms indicated a significant linear effect of time, such that participants demonstrated significant decreases over time in PTSD symptoms, regardless of treatment modality.ConclusionOur preliminary investigation provides support for the feasibility and efficacy of an integrated approach to treating EDs and PTSD. It is critical for future work to undertake randomized tests of this integrated approach using large, heterogeneous samples.Level of evidenceLevel IV, multiple time series with intervention.

Several proteins have proven useful as blood-based biomarkers to assist in evaluation and management of traumatic brain injury (TBI). The objective of this study was to determine whether two day-of-injury blood-based biomarkers are predictive of posttraumatic stress disorder (PTSD). We used data from 1143 individuals with mild TBI (mTBI; defined as admission Glasgow Coma Scale [GCS] score 13-15) enrolled in TRACK-TBI, a prospective longitudinal study of level 1 trauma center patients. Plasma glial fibrillary acidic protein (GFAP) and serum high sensitivity C-reactive protein (hsCRP) were measured from blood collected within 24 h of injury. Two hundred and twenty-seven (19.9% of) patients had probable PTSD (PCL-5 score ≥ 33) at 6 months post-injury. GFAP levels were positively associated (Spearman's rho = 0.35, p

BackgroundChild maltreatment recidivism substantially increases the likelihood of adverse life outcomes, but there is little evidence that family preservation services are effective at reducing recidivism. Mothers in child welfare have very high rates of trauma exposure; maternal post-traumatic stress disorder (PTSD) is an intervention target that has the potential to reduce abuse and neglect. The Safe Mothers, Safe Children (SMSC) intervention program involves the delivery of an innovative combination of interventions, including Skills Training in Affective and Interpersonal Regulation (STAIR) and Parent-Child Interaction Therapy (PCIT). The combined intervention, Parenting-STAIR (P-STAIR), targets maternal PTSD and comorbid depression symptoms to reduce the adverse effects of PTSD on parenting, improve positive parenting skills, and prevent maltreatment recidivism.MethodsThis study is a two-arm randomized controlled trial: P-STAIR (23 sessions) versus supportive counseling (23 sessions). Participants are mothers receiving child welfare family preservation services (FPS), with a child in the age range of 1-8 years old and meeting diagnostic criteria for PTSD (with/without depression). Clinical assessment occurs at pre-treatment (baseline), two in-treatment assessments (mid-assessment #1 after module 9 and mid-assessment #2 after module 15), post-treatment, and at a 6-month follow-up. Recidivism will be measured using the New York State Child Welfare Registry (NYSCWR). We will enroll a total of 220 participants over 4 years: half (N = 110) randomly assigned to the P-STAIR condition and half (N = 110) to the supportive counseling condition.DiscussionThis is the first RCT to investigate the efficacy of P-STAIR. The findings for the trial have the potential to contribute to the expansion of evidence-based practices for maternal PTSD, maltreatment, and child welfare.

BackgroundPosttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences of psychological trauma exposure. The disorders have high genetic overlap. Trauma is a complex phenotype but research suggests that trauma sensitivity has a heritable basis. We investigated whether sensitivity to trauma in those with MDD reflects a similar genetic component in those with PTSD.MethodsGenetic correlations between PTSD and MDD in individuals reporting trauma and MDD in individuals not reporting trauma were estimated, as well as with recurrent MDD and single-episode MDD, using genome-wide association study (GWAS) summary statistics. Genetic correlations were replicated using PTSD data from the Psychiatric Genomics Consortium and the Million Veteran Program. Polygenic risk scores were generated in UK Biobank participants who met the criteria for lifetime MDD (N = 29 471). We investigated whether genetic loading for PTSD was associated with reporting trauma in these individuals.ResultsGenetic loading for PTSD was significantly associated with reporting trauma in individuals with MDD [OR 1.04 (95% CI 1.01-1.07), Empirical-p = 0.02]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in individuals not reporting trauma (rg differences = ~0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced single-episode MDD (χ2 > 166, p < 0.001).ConclusionsOur findings point towards the existence of genetic variants associated with trauma sensitivity that might be shared between PTSD and MDD, although replication with better powered GWAS is needed. Our findings corroborate previous research highlighting trauma exposure as a key risk factor for recurrent MDD.

Prior research suggests that people with Posttraumatic Stress Disorder (PTSD) may experience a form of accelerated biological aging. In other populations, loneliness has been shown to elevate risk for many of the same components of accelerated biological aging, and other deleterious outcomes, as seen in people with PTSD. Although standard diagnostic criteria for PTSD include "feelings of detachment or estrangement from others", the relationship of such feelings to the concept of loneliness remains uncertain, in par potentially due to a failure to distinguish between loneliness versus objective social isolation. In order to catalyze wider research attention to loneliness in PTSD, and the potential contribution to accelerated biological aging, the present paper provides three components: (1) a conceptual overview of the relevant constructs and potential interrelationships, (2) a review of the limited extant empirical literature, and (3) suggested directions for future research. The existing empirical literature is too small to support many definitive conclusions, but there is evidence of an association between loneliness and symptoms of PTSD. The nature of this association may be complex, and the causal direction(s) uncertain. Guided by the conceptual overview and review of existing literature, we also highlight key areas for further research. The ultimate goal of this line of work is to elucidate mechanisms underlying any link between loneliness and accelerated aging in PTSD, and to develop, validate, and refine prevention and treatment efforts.

Trauma-exposed veterans receiving mental health care may have an elevated risk of experiencing COVID-19-related difficulties. Using data from several ongoing clinical trials (N = 458), this study examined exposure to COVID-19-related stressors and their associations with key sociodemographic factors and mental health outcomes. The results showed that exposure to COVID-19-related stressors was common, higher among veterans who were racial/ethnic minorities d = 0.32, and associated with elevated posttraumatic stress disorder (PTSD), r = .288, and depressive symptom severity, r = .246. Women veterans experienced more difficulty accessing social support, d = 0.31, and higher levels of COVID-19-related distress, d = 0.31, than men. Qualitative data were consistent with survey findings and highlighted the broader societal context in veterans' experience of COVID-19-related distress. These findings may inform future research on the impact of the pandemic on veterans, particularly those who are women and members of minoritized racial/ethnic groups, as well as mental health treatment planning for this population.

The current study investigates whether prepregnancy maternal posttraumatic stress disorder (PTSD) symptoms, depressive symptoms, and stress predict children's cortisol diurnal slopes and cortisol awakening responses (CARs) adjusting for relevant variables. Mothers were enrolled after delivering a baby and followed through their subsequent pregnancy with 5 years of longitudinal data on their subsequent child. This prospective design allowed assessment of PTSD symptoms, depressive symptoms, and perceived stress prior to pregnancy. Children provided three saliva samples per day on three consecutive days at two timepoints in early childhood (M age = 3.7 years, SD = 0.38; M age = 5.04 years, SD = 0.43). Mothers' PTSD symptoms prior to pregnancy were significantly associated with flatter child diurnal cortisol slopes at 4 and 5 years, but not with child CAR. Findings at the age of 4 years, but not 5 years, remained statistically significant after adjustment for maternal socioeconomic status, race/ethnicity, child age, and other covariates. In contrast, maternal prepregnancy depressive symptoms and perceived stress did not significantly predict cortisol slopes or CAR. Results suggest that maternal prepregnancy PTSD symptoms may contribute to variation in early childhood physiology. This study extends earlier work demonstrating risk of adverse outcomes among children whose mothers experienced trauma but associations cannot be disentangled from effects of prenatal mental health of mothers on children's early childhood.