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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.

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

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.

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.

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.

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.

BackgroundInterest in complementary and integrative health (CIH) approaches, such as meditation, yoga, and acupuncture, continues to grow. The evidence of effectiveness for some CIH approaches has increased in the last decade, especially for pain, with many being recommended in varying degrees in national guidelines. To offer nonpharmacological health management options and meet patient demand, the nation's largest integrated healthcare system, the Veterans Health Administration (VA), greatly expanded their provision of CIH approaches recently.ObjectiveThis paper addressed the questions of how many VA patients might use CIH approaches and chiropractic care if they were available at modest to no fee, and would patients with some health conditions or characteristics be more likely than others to use these therapies.DesignUsing electronic medical records, we conducted a national, three-year, retrospective analysis of VA patients' use of eleven VA-covered therapies: chiropractic care, acupuncture, Battlefield Acupuncture, biofeedback, clinical hypnosis, guided imagery, massage therapy, meditation, Tai Chi/Qigong, and yoga.ParticipantsWe created a national cohort of veterans using VA healthcare from October 2016-September 2019.Key resultsVeterans' use of these approaches increased 70% in three years. By 2019, use was 5.7% among all VA patients, but highest among patients with chronic musculoskeletal pain (13.9%), post-traumatic stress disorder (PTSD; 10.6%), depression (10.4%), anxiety (10.2%), or obesity (7.8%). The approach used varied by age and race/ethnicity, with women being uniformly more likely than men to use each approach. Patients having chronic musculoskeletal pain, obesity, anxiety, depression, or PTSD were more likely than others to use each of the approaches.ConclusionsVeterans' use of some approaches rapidly grew recently and was robust, especially among patients most in need. This information might help shape federal/state health policy on the provision of evidence-based CIH approaches and guide other healthcare institutions considering providing them.

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.

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.

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.

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.

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.

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.

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

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.

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.

Post-traumatic stress disorder (PTSD) is associated with an increased risk for physical illnesses and early mortality. However, we do not know if it also increases the risk for adverse outcomes of coronavirus disease 2019 (COVID-19). In this retrospective cohort study, we examined associations of PTSD and other psychiatric disorders with risk for hospitalization and death in the 60 days following a COVID-19 infection in 228,367 U.S. Department of Veteran Affairs (VA) patients who tested positive for COVID-19 between February 2020 and August 2021 (age m = 60.6, 89.5% male). Generalized linear models estimated associations of PTSD and other psychiatric disorders with outcomes following a positive SARS-CoV-2 test, adjusting for socio-demographic, medical, and behavioral factors. Among 228,367 VA patients, 25.6% had PTSD, and 28.2% had a psychiatric disorder other than PTSD. In the 60 days following a positive COVID-19 test, 15% of patients were hospitalized, and 6% died. Patients with PTSD had an increased risk for both hospitalization (adjusted relative risk, ARR = 1.18, 95% CI 1.15-1.21) and death (ARR = 1.13, 95% CI 1.08-1.19) relative to those with no psychiatric disorders, adjusting for socio-demographics. Estimates remained significant when models were additionally adjusted for medical comorbidities and smoking. Patients with other psychiatric disorders also had an increased risk of adverse COVID-19 outcomes, with larger effect sizes than PTSD in older (≥65 years) but not younger patients. In this large-scale study of VA patients, individuals with PTSD, and other psychiatric disorders, had heightened vulnerability to severe adverse outcomes of COVID-19; thus, individuals with PTSD should also be considered at higher risk for severe COVID-19 outcomes, and potentially prioritized for vaccination, screening, and early treatment intervention for COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is a global health crisis with the potential to elicit and worsen psychiatric symptoms, particularly post-traumatic stress disorder (PTSD) symptoms. Identifying modifiable protective factors is critical for preventing and treating PTSD symptoms both during and following the COVID-19 pandemic. The present study examined associations of self-reported sleep quality and anticipatory threat appraisals of the pandemic with PTSD symptoms 6 months later in a sample enriched for pre-pandemic trauma exposure and PTSD. The sample included 590 adults (mean age 38.2 years) who completed a baseline survey in August/September 2020 and follow-up survey in March/April 2021. The sample was recruited from a pool of participants interested in a prior study about traumatic stress. Participants self-reported sleep quality and pandemic-related anticipatory threat appraisals at baseline. PTSD symptoms were assessed at baseline and follow-up. Baseline sleep quality was associated with PTSD symptoms at follow-up controlling for baseline PTSD symptoms (B = -2.49, p = 0.001). Perceived anticipatory threat of the pandemic moderated this association such that worse sleep quality was related to more severe PTSD symptoms at follow-up for participants with higher (B = -4.07, p

Posttraumatic stress disorder (PTSD) has been increasingly recognized as a potential mental health concern for new mothers. Elevated PTSD symptoms have been associated with maladaptive coping strategies in the postpartum period, a time when women face many challenges, demands, and stressors. However, PTSD symptoms manifest in heterogeneous ways, and focusing only on total symptom scores may obscure more nuanced associations with particular coping styles. In a large, ethnically diverse sample of postpartum women from across the United States (N = 1,315), first we examined associations between total PTSD symptom severity with three distinct coping styles: active-emotional, avoidant-emotional, and problem-focused. In models adjusting for race and educational attainment, total PTSD symptom severity was significantly positively associated with tendencies to use active- and avoidant-emotional, but not problem-focused, coping. We then adopted a novel "symptomics" approach, employing relative importance analyses to examine associations between individual PTSD symptoms with the coping styles. These analyses identified PTSD symptoms that were most strongly associated with each coping style. Notably, whereas several symptoms explained variance in avoidant-emotional coping, only a few symptoms contributed most to active-emotional and problem-focused coping. Moreover, non-specific symptoms of PTSD that are shared with other psychopathology (e.g., difficulty concentrating, loss of interest) explained significant proportions of variance across all coping styles. Collectively, results suggest that a symptomics approach may provide more nuanced insight into how PTSD symptoms are linked to various coping styles in postpartum women, which can help inform potential screening and intervention targets for at-risk women during this period.

Acts of violence are the fifth leading cause of nonfatal occupational injuries in the United States. Experiencing a traumatic event at work can have serious mental health consequences, including the development of posttraumatic stress disorder (PTSD). This study aimed to quantify the prevalence of PTSD caused by workplace violence (WPV) in a statewide workers' compensation system and compare the outcomes and treatment of WPV cases versus those caused by other traumatic events. Using a retrospective cohort study design, workers who reported PTSD as the primary reason for a workers' compensation claim and had no coexisting physical injuries were found in California during 2009-2018. A total of 3,772 PTSD cases were identified, 48.9% of which were attributed to WPV. Demographic risk factors associated with WPV PTSD included lower income, younger age, female gender, and employment in retail or finance, p < .001-p = .007. For individuals who returned to work, claims due to WPV resulted in longer medically approved time away from work than non-WPV causes (Mdn = 132.5 days vs. Mdn = 91 days, respectively), p < .001. Three of the top 10 most frequently prescribed medications were administered against evidence-based guidelines. This study found that many treatments prescribed to PTSD patients are based on insufficient evidence, and the provision of existing empirically supported treatments is needed, particularly in generalized populations. The findings support the need for additional recognition of the cause of workplace PTSD to facilitate appropriate referrals to WPV or PTSD specialists to support return-to-work efforts.

BackgroundRecent studies in both human and experimental animals have identified fragmented and unpredictable parental and environmental signals as a novel source of early-life adversity. Early-life unpredictability may be a fundamental developmental factor that impacts brain development, including reward and emotional memory circuits, affecting the risk for psychopathology later in life. Here, we tested the hypothesis that self-reported early-life unpredictability is associated with psychiatric symptoms in adult clinical populations.MethodsUsing the newly validated Questionnaire of Unpredictability in Childhood, we assessed early-life unpredictability in 156 trauma-exposed adults, of which 65% sought treatment for mood, anxiety, and/or posttraumatic stress disorder (PTSD) symptoms. All participants completed symptom measures of PTSD, depression and anhedonia, anxiety, alcohol use, and chronic pain. Relative contributions of early-life unpredictability versus childhood trauma and associations with longitudinal outcomes over a 6-month period were determined.ResultsEarly-life unpredictability, independent of childhood trauma, was significantly associated with higher depression, anxiety symptoms, and anhedonia, and was related to higher overall symptom ratings across time. Early-life unpredictability was also associated with suicidal ideation, but not alcohol use or pain symptoms.ConclusionsEarly-life unpredictability is an independent and consistent predictor of specific adult psychiatric symptoms, providing impetus for studying mechanisms of its effects on the developing brain that promote risk for psychopathology.

BackgroundAlthough research has shown that exposure to potentially traumatic and morally injurious events is associated with psychological symptoms among veterans, knowledge regarding functioning impacts remains limited.MethodsA population-based sample of post-9/11 veterans completed measures of intimate relationship, health, and work functioning at approximately 9, 15, 21, and 27 months after leaving service. Moral injury, posttraumatic stress, and depression were assessed at ~9 months post-separation. We used Latent Growth Mixture Models to identify discrete classes characterized by unique trajectories of change in functioning over time and to examine predictors of class membership.ResultsVeterans were assigned to one of four functioning trajectories: high and stable, high and decreasing, moderate and increasing, and moderate and stable. Whereas posttraumatic stress, depression, and moral injury associated with perpetration and betrayal predicted worse outcomes at baseline across multiple functioning domains, moral injury associated with perpetration and depression most reliably predicted assignment to trajectories characterized by relatively poor or declining functioning.ConclusionsMoral injury contributes to functional problems beyond what is explained by posttraumatic stress and depression, and moral injury due to perpetration and depression most reliably predicted assignment to trajectories characterized by functional impairment over time.

BackgroundAmong the renewed applications of psychedelic medicines in psychiatry, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for posttraumatic stress disorder (PTSD) has demonstrated the most promise in early small-scale studies. Recent exploratory analyses from prior clinical trials of MDMA-assisted therapy for PTSD have suggested that recent use of selective serotonin reuptake inhibitors (SSRIs)-the only medication class with United States Food and Drug Administration (FDA) approval to treat PTSD-can significantly dampen the efficacy of this novel therapy. Although psychedelic medicines are not yet FDA approved, MDMA is very likely to be the first to achieve FDA approval-perhaps within the next 2 years. Given this timeline, the field would benefit from more knowledge about potential interactions between this novel therapy and our current treatments.MethodsThis brief report reviews selected literature in the basic and clinical neurosciences relevant to the interaction of SSRIs and MDMA.FindingsThe possibility that SSRI use could dampen future responses to MDMA-assisted therapy for PTSD raises many important questions about the biological mechanisms as well as ethical implications around the most appropriate way to counsel patients. In this brief report, we compare the evidence for SSRIs and MDMA-assisted therapy in the treatment of PTSD and discuss what is known about the neurobiological interactions between these 2 medicines.ConclusionsThere is strong neurobiological plausibility for the hypothesis that chronic SSRI use dampens response to MDMA-assisted therapy, although current knowledge in the field is limited and primarily relates to acute pharmacodynamic interactions. Our commentary highlights the urgent need for future work dedicated to addressing this important clinical topic.

ObjectiveThis study aimed to investigate the effect of brief reminder-focused positive psychiatry and suicide prevention (RFPP-S) on suicidal ideation, posttraumatic stress disorder (PTSD) symptoms, and clinical outcomes among youths with PTSD treated in psychiatric emergency rooms.MethodsThis study included youths with PTSD and suicidality who received either RFPP-S (N=50) or treatment as usual (N=150). The Columbia Suicide Severity Rating Scale (C-SSRS), Clinician-Administered PTSD Scale for children and adolescents, University of California, Los Angeles Trauma Reminder Inventory, Patient Health Questionnaire-9, Positive Emotion, Engagement, Relationships, Meaning, and Accomplishment Scale, and positive psychiatry test batteries were administered at baseline, on day 2, and 1 week and 1 month after discharge.ResultsOn day 2, the RFPP-S group showed a greater reduction in PTSD symptoms (55%) and reactivity to trauma and loss reminders (80%) compared with the control group (10% for both) (p=0.001). A significantly greater reduction in C-SSRS score for RFPP-S (80%), compared with treatment as usual (15%), was noted (p=0.001), and RFPP-S showed more rapid stabilization (mean±SD=2.0±0.5 days) and enhanced postdischarge follow-up (100%) compared with treatment as usual (5.0±2.0 days and 50%, respectively) (p

ObjectivesThis study of people with HIV (PWH) and those without HIV conducted during the COVID-19 pandemic in the United States in 2020 examines the impact of posttraumatic stress disorder (PTSD) on COVID-19 burden, defined as pandemic-related disruptions.MethodsData consisted of survey responses on PTSD among participants (N = 2434) enrolled in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV (WIHS) cohorts. Unadjusted and adjusted regression models were used to examine the association of PTSD with COVID-19 burden (overall and domain-specific burdens). Quasi-Poisson regression models were used to assess associations with the COVID-19 burden score and 2 domain-specific burdens: (1) changes in resources and (2) interruptions in health care. Analyses was adjusted for age, race/ethnicity, HIV serostatus, current smoking status, number of comorbidities, education, and study regions.ResultsStudy participants were a median age of 58 (interquartile range, 52-65) years. In both bivariate and multivariable models, PTSD severity was associated with greater overall COVID-19 burden. PTSD severity was associated with the number of resource changes and number of interruptions in medical care. These findings were also consistent across cohorts (MACS/WIHS) and across HIV serostatus, suggesting a greater risk for COVID-19 burden with greater PTSD severity, which remained significant after controlling for covariates.ConclusionsThis study builds on emerging literature demonstrating the impact of mental health on the burden and disruption associated with the COVID-19 pandemic, providing context specific to PWH. The ongoing pandemic requires structural and social interventions to decrease disruption to resources and health resource needs among these vulnerable populations.

Increasingly, lesbian, gay, and bisexual (LGB) individuals are fleeing the 67 countries that criminalize consensual same-sex intimate relationships, seeking asylum in countries such as the United States. Minority stress theory posits that compared with non-LGB refugees and asylum seekers (RAS), LGB RAS are likely to face persecution, rejection, and discrimination and have a higher risk of experiencing posttraumatic stress disorder (PTSD) symptoms. This study assessed differences in sociodemographic characteristics, persecution experiences, and mental health outcomes among 959 RAS persecuted for same-sex behavior (pLGB RAS) who presented for care and social services at the Boston Center for Refugee Health and Human Rights. Data were derived from intake interviews with RAS clients that elicited torture experiences and assessed PTSD symptoms using the Short Screening Scale for PTSD. Over 11% of the total sample were pLGB RAS. Compared with non-pLGB RAS, pLGB RAS reported higher PTSD symptom levels, β = .08, p = .031; more difficulty loving others, d = 0.13, p < .001; and feeling more isolated, d = 0.10, p = .005. pLGB RAS reported more persecution, d = 0.31, p = .002; physical assaults, d = 0.22, p = .029; and psychological assaults, d = 0.20, p = .047; and were more likely to be asylum seekers, d = 0.11, p = .001, and have experienced persecution in Uganda, d = 0.39, p < .001, and other countries that criminalize same-sex acts, d = 0.26, p < .001. More research is needed to understand clinical outcomes and implications of treatment for this population.

BackgroundUnderstanding the long-term sequelae of severe COVID-19 remains limited, particularly in the United States.ObjectiveTo examine long-term outcomes of patients who required intensive care unit (ICU) admission for severe COVID-19.Design, patients, and main measuresThis is a prospective cohort study of patients who had severe COVID-19 requiring an ICU admission in a two-hospital academic health system in Southern California. Patients discharged alive between 3/21/2020 and 12/31/2020 were surveyed approximately 6 months after discharge to assess health-related quality of life using Patient-Reported Outcomes Measurement Information System (PROMIS®)-29 v2.1, post-traumatic stress disorder (PTSD) and loneliness scales. A preference-based health utility score (PROPr) was estimated using 7 PROMIS domain scores. Patients were also asked their attitude about receiving aggressive ICU care.Key resultsOf 275 patients admitted to the ICU for severe COVID-19, 205 (74.5%) were discharged alive and 132 (64%, median age 59, 46% female) completed surveys a median of 182 days post-discharge. Anxiety, depression, fatigue, sleep disturbance, ability to participate in social activities, pain interference, and cognitive function were not significantly different from the U.S. general population, but physical function (44.2, SD 11.0) was worse. PROPr mean score of 0.46 (SD 0.30, range -0.02 to 0.96 [

Background/objectiveThe present study leveraged the expertise of an international group of posttraumatic stress and substance use disorder (PTSD+SUD) intervention researchers to identify which methods of categorizing interventions which target SUD, PTSD, or PTSD+SUD for populations with both PTSD+SUD may be optimal for advancing future systematic reviews, meta-analyses, and comparative effectiveness studies which strive to compare effects across a broad variety of psychotherapy types.MethodA two-step process was used to evaluate the categorization terminology. First, we searched the literature for pre-existing categories of PTSD+SUD interventions from PTSD+SUD clinical trials, systematic and literature reviews. Then, we surveyed international trauma and substance use subject matter experts about their opinions on pre-existing intervention categorization and ideal categorization nomenclature.ResultsMixed method analyses revealed that a proliferation of PTSD+SUD treatment research over the last twenty years brought with it an abundance of ways to characterize the treatments that have been evaluated. Results from our survey of experts (N = 27) revealed that interventions for PTSD+SUD can be classified in many ways that appear to overlap highly with one another. Many experts (11/27; 41%) selected the categories of 'trauma-focused and non-trauma focused' as an optimal way to distinguish treatment types. Although several experts reinforced this point during the subsequent meeting, it became clear that no method of categorizing treatments is without flaws.ConclusionOne possible categorization (trauma-focused/non-trauma focused) was identified. Revised language and nomenclature for classification of PTSD+SUD treatments are needed in order to accommodate the needs of this advancing field.

Genome-wide association studies (GWAS) have identified several risk loci for post-traumatic stress disorder (PTSD); however, how they confer PTSD risk remains unclear. We aimed to identify genes that confer PTSD risk through their effects on brain protein abundance to provide new insights into PTSD pathogenesis. To that end, we integrated human brain proteomes with PTSD GWAS results to perform a proteome-wide association study (PWAS) of PTSD, followed by Mendelian randomization, using a discovery and confirmatory study design. Brain proteomes (N = 525) were profiled from the dorsolateral prefrontal cortex using mass spectrometry. The Million Veteran Program (MVP) PTSD GWAS (n = 186,689) was used for the discovery PWAS, and the Psychiatric Genomics Consortium PTSD GWAS (n = 174,659) was used for the confirmatory PWAS. To understand whether genes identified at the protein-level were also evident at the transcript-level, we performed a transcriptome-wide association study (TWAS) using human brain transcriptomes (N = 888) and the MVP PTSD GWAS results. We identified 11 genes that contribute to PTSD pathogenesis via their respective cis-regulated brain protein abundance. Seven of 11 genes (64%) replicated in the confirmatory PWAS and 4 of 11 also had their cis-regulated brain mRNA levels associated with PTSD. High confidence level was assigned to 9 of 11 genes after considering evidence from the confirmatory PWAS and TWAS. Most of the identified genes are expressed in other PTSD-relevant brain regions and several are preferentially expressed in excitatory neurons, astrocytes, and oligodendrocyte precursor cells. These genes are novel, promising targets for mechanistic and therapeutic studies to find new treatments for PTSD.

Psychedelics are increasingly being recognized for their potential to treat a wide range of brain disorders including depression, post-traumatic stress disorder (PTSD), and substance use disorder. Their broad therapeutic potential might result from an ability to rescue cortical atrophy common to many neuropsychiatric and neurodegenerative diseases by impacting neurotrophic factor gene expression, activating neuronal growth and survival mechanisms, and modulating the immune system. While the therapeutic potential of psychedelics has not yet been extended to neurodegenerative disorders, we provide evidence suggesting that approaches based on psychedelic science might prove useful for treating these diseases. The primary target of psychedelics, the 5-HT2A receptor, plays key roles in cortical neuron health and is dysregulated in Alzheimer's disease. Moreover, evidence suggests that psychedelics and related compounds could prove useful for treating the behavioral and psychological symptoms of dementia (BPSD). While more research is needed to probe the effects of psychedelics in models of neurodegenerative diseases, the robust effects of these compounds on structural and functional neuroplasticity and inflammation clearly warrant further investigation.

A substantial minority of women who experience interpersonal violence will develop posttraumatic stress disorder (PTSD). One critical challenge for preventing PTSD is predicting whose acute posttraumatic stress symptoms will worsen to a clinically significant degree. This 6-month longitudinal study adopted multilevel modeling and exploratory machine learning (ML) methods to predict PTSD onset in 58 young women, ages 18 to 30, who experienced an incident of physical and/or sexual assault in the three months prior to baseline assessment. Women completed baseline assessments of theory-driven cognitive and neurobiological predictors and interview-based measures of PTSD diagnostic status and symptom severity at 1-, 3-, and 6-month follow-ups. Higher levels of self-blame, generalized anxiety disorder severity, childhood trauma exposure, and impairment across multiple domains were associated with a pattern of high and stable posttraumatic stress symptom severity over time. Predictive performance for PTSD onset was similarly strong for a gradient boosting machine learning model including all predictors and a logistic regression model including only baseline posttraumatic stress symptom severity. The present findings provide directions for future work on PTSD prediction among interpersonal violence survivors that could enhance early risk detection and potentially inform targeted prevention programs.

Understanding correlates of COVID-19 vaccine intentions is critical for increasing vaccine uptake. Given associations of trauma exposure and posttraumatic stress disorder (PTSD) with alterations in threat sensitivity and health behaviors, we hypothesized they could influence COVID-19 vaccine acceptance and hesitancy and be important variables to consider in the design of vaccination campaigns. Data came from a longitudinal online study of 544 US adults with high levels of pre-pandemic trauma and PTSD, assessed in August/September 2020 and March/April 2021. Individuals reported socio-demographic factors, pandemic factors, lifetime trauma history and PTSD symptoms, and COVID-19 vaccinations or intentions. We estimated bivariate associations between socio-demographics, pandemic factors, and trauma and PTSD symptoms at baseline and follow-up with COVID-19 vaccine acceptance versus hesitancy (i.e., vaccinated against COVID-19 or willing to get vaccinated versus unsure or unwilling to get vaccinated) six months later. Multiple socio-demographics (e.g., race/ethnicity, income, education, political preference) and pandemic factors (e.g., perceived likelihood of infection, household COVID-19 infection) were associated with COVID-19 vaccine hesitancy (27.2% were hesitant). However, trauma history, PTSD symptoms, and other mental health factors were not associated with COVID-19 vaccine acceptance versus hesitancy. Socio-demographic and pandemic-related factors appear more important than trauma or mental health for understanding COVID-19 vaccine intentions.

Objective: The co-occurrence of substance use disorders (SUD) and trauma-exposure is a risk factor for suicidal thoughts and behaviors (STB). However, traditional methods of measurement for suicidal thoughts and behaviors are limited by an overreliance on dichotomous (i.e., yes or no) and averaged/summed scale score measurements. Further, among trauma-exposed individuals with SUD, it remains unclear which specific demographic factors, types of SUDs, and trauma sequelae (e.g., posttraumatic stress disorder [PTSD] symptom clusters) may be associated with elevated STB. The present study utilized item response theory to (a) generate empirically derived STB severity scores and, (b) examine which demographic factors, SUD diagnoses, and DSM-IV PTSD symptom clusters are associated with suicidality in a trauma-exposed sample with SUDs. Method: Female trauma-exposed participants with SUDs (N = 544) were recruited from community substance use treatment facilities in the National Drug Abuse Treatment Clinical Trials Network (CTN). Clinician-administered interviews assessed STB, SUDs, and PTSD symptoms. Results: Results indicated that the unidimensional item response theory (IRT) model used to estimate latent STB severity scores fit well, with strong local reliability at higher levels of latent STB severity. Regression predictors of elevated STB severity included younger age, opioid dependence, and higher PTSD reexperiencing symptoms. Conclusions: Clinicians are advised to screen for and target opioid use disorders and reexperiencing symptoms when addressing suicidal thoughts and behavior in trauma-exposed individuals with SUDs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Multiple factor analytic and item response theory studies have shown that items/symptoms vary in their relative clinical weights in structured interview measures for posttraumatic stress disorder (PTSD). Despite these findings, the use of total scores, which treat symptoms as though they are equally weighted, predominates in practice, with the consequence of undermining the precision of clinical decision-making. We conducted an integrative data analysis (IDA) study to harmonize PTSD structured interview data (i.e., recoding of items to a common symptom metric) from 25 studies (total N = 2,568). We aimed to identify (a) measurement noninvariance/differential item functioning (MNI/DIF) across multiple populations, psychiatric comorbidities, and interview measures simultaneously and (b) differences in inferences regarding underlying PTSD severity between scale scores estimated using moderated nonlinear factor analysis (MNLFA) and a total score analog model (TSA). Several predictors of MNI/DIF impacted effect size differences in underlying severity across scale scoring methods. Notably, we observed MNI/DIF substantial enough to bias inferences on underlying PTSD severity for two groups: African Americans and incarcerated women. The findings highlight two issues raised elsewhere in the PTSD psychometrics literature: (a) bias in characterizing underlying PTSD severity and individual-level treatment outcomes when the psychometric model underlying total scores fails to fit the data and (b) higher latent severity scores, on average, when using DSM-5 (net of MNI/DIF) criteria, by which multiple factors (e.g., Criterion A discordance across DSM editions, changes to the number/type of symptom clusters, changes to the symptoms themselves) may have impacted severity scoring for some patients.

IntroductionSubsyndromal PTSD (sub-PTSD) is associated with functional impairment and increased risk for full PTSD. This study examined factors associated with progression from sub-PTSD to full PTSD symptomatology among previously deployed military veterans.Materials and methodsData were drawn from a longitudinal survey of Navy and Marine Corps personnel leaving military service between 2007 and 2010 administered immediately before separation (baseline) and ~1 year later (follow-up). Survey measures assessed PTSD symptoms at both times; the baseline survey also assessed potential predictors of symptom change over time. Logistic regression models were used to identify predictors of progression from sub-PTSD to full PTSD status.ResultsCompared to those with no or few PTSD symptoms at baseline, individuals with sub-PTSD were almost three times more likely to exhibit full PTSD symptomatology at follow-up. Risk factors for symptom increase among those with sub-PTSD included moderate or high levels of combat exposure and utilization of fewer positive coping behaviors. Use of prescribed psychotropic medication was protective against symptom increase.ConclusionThis study identified several predictors of symptom increase in military veterans with sub-PTSD. Interventions targeting modifiable risk factors for symptom escalation, including behavioral and pharmacological treatments, may reduce rates of new-onset PTSD in this population.

BackgroundDispositional gratitude has been implicated as a psychological characteristic that may modulate risk for mental health outcomes. Using a population-based sample of U.S. military veterans, this study evaluated the association between dispositional gratitude and the development of psychopathology and suicidal behaviors over a 7-year period.MethodsA nationally representative sample of U.S. veterans was surveyed at four timepoints across seven years. Analyses were restricted to veterans without incident outcomes at baseline. Multivariable analyses were conducted to examine the relation between baseline levels of dispositional gratitude and risk of developing (a) major depressive disorder (MDD), generalized anxiety disorder (GAD), or posttraumatic stress disorder (PTSD); (b) suicidal ideation; and (c) suicide attempts.ResultsA total 9.6% of veterans developed MDD, GAD, and/or PTSD, 9.5% developed suicidal ideation, and 2.8% reported having attempted suicide over the 7-year follow-up period. Among veterans with high levels of dispositional gratitude, incidence was lower for MDD/GAD/PTSD (8.0%), suicidal ideation (6.8%), and suicide attempts (1.5%). Conversely, veterans with low dispositional gratitude were at substantially higher risk of developing MDD/GAD/PTSD (27.7%), suicidal ideation (33.6%), and suicide attempts (20.3%).ConclusionsHigh dispositional gratitude may help protect against the development of psychopathology and suicidal behaviors in U.S. military veterans, whereas low gratitude may increase risk of developing these outcomes. Collectively, these results support the potential utility of enhancing gratitude as part of primary prevention efforts for veterans, service members, and other populations at heightened risk for adverse mental health outcomes.

Posttraumatic negative thoughts about one's self and the world are related to posttraumatic stress disorder (PTSD) symptom severity and change in cognitive behavioral treatment (CBT), but little is known about this association when CBT is delivered with medication. The current study presents a planned comparison of changes in negative posttraumatic thoughts during (a) prolonged exposure (PE) plus pill placebo (PE+PLB), (b) sertraline plus enhanced medication management (SERT+EMM), and (c) PE plus sertraline (PE+SERT) as part of a randomized clinical trial in a sample of 176 veterans. Lagged regression modeling revealed that change in posttraumatic negative thoughts was associated with PTSD symptom change in the conditions in which participants received sertraline, ds = 0.14-0.25, ps = 0.04-.001). However, contrary to previous research, the models that started with symptom change were also statistically significant, d = 0.23, p