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Current pharmacological treatments against post-traumatic stress disorder (PTSD) lack adequate efficacy. As a result, intense research has focused on identifying other molecular pathways mediating the pathogenesis of this condition. One such pathway is neuroinflammation, which has demonstrated a role in PTSD pathogenesis by causing synaptic dysfunction, neuronal death, and functional impairment in the hippocampus. Phosphodiesterase (PDE) inhibitors (PDEIs) have emerged as promising therapeutic agents against neuroinflammation in other neurological conditions. Furthermore, PDEIs have shown some promise in animal models of PTSD. However, the current model of PTSD pathogenesis, which is based on dysregulated fear learning, implies that PDE inhibition in neurons should enhance the acquisition of fear memory from the traumatic event. As a result, we hypothesized that PDEIs may improve PTSD symptoms through inhibiting neuroinflammation rather than long-term potentiation-related mechanisms. To this end, we tested the therapeutic efficacy of cilostazol, a selective inhibitor of PDE3, on PTSD-related anxiety symptoms in the underwater trauma model of PTSD. PDE3 is expressed much more richly in microglia and astrocytes compared to neurons in the murine brain. Furthermore, we used hippocampal indolamine 2,3-dioxygenase 1 (IDO) expression and interleukin 1 beta (IL-1β) concentration as indicators of neuroinflammation. We observed that cilostazol pretreatment prevented the development of anxiety symptoms and the increase in hippocampal IDO and IL-1β following PTSD induction. As a result, PDE3 inhibition ameliorated the neuroinflammatory processes involved in the development of PTSD symptoms. Therefore, cilostazol and other PDEIs may be promising candidates for further investigation as pharmacological therapies against PTSD. [ABSTRACT FROM AUTHOR]

In order for the innovation policymakers to design and fulfill suitable interventions in the community's psychological management, which is affected by the Covid-19 pandemic, it is necessary to monitor all information about different groups of the community quickly, in a comprehensive and classified manner in other times. The aim of this study is to develop a questionnaire to evaluate distress levels like this. Considering the RIU knowledge transfer model and using a researcher-designed questionnaire to assess distress levels in the general population and healthcare workers, an online survey was conducted in the summer of 2019 in Tehran province. In the general population, in the study period, all independent variables, including socio-economic stress, respect to health protocols, trust in healthcare officials and job distress of medical staff, have significant effects on general distress. The socio-economic stress variable had the greatest impact. The regression model from this study allows the policymaker to estimate the general distress level of the society according to the independent variables studied. Despite the high effect of stressors, the study population's psychological resilience level is acceptable during the study period. They still trust healthcare officials and respect health protocols. However, considering the differences in the findings of various studies on distress level and it is strengthening factors show the need for accurate and continuous monitoring of societal changes at different times of the pandemic. [ABSTRACT FROM AUTHOR]

Aim: To investigate the mental well‐being of early career nurses working in the United Kingdom during the COVID‐19 pandemic, with a particular emphasis on symptoms related to post‐traumatic stress disorder. Design: A longitudinal survey study. Methods: Data were acquired at three timepoints during the COVID‐19 pandemic (between May 2020 and March 2021) to determine whether symptoms of post‐traumatic stress disorder persisted over time. Quantitative measures of well‐being were supplemented with survey data on the nurses' experiences of working during the pandemic. Results: Twenty‐seven per cent of participants suffered from persistent symptoms of post‐traumatic stress while working as nurses during the pandemic. The nurses' baseline resilience, as well as their perception of the quality of their work environment, were significant negative predictors of symptoms of post‐traumatic stress. Participants identified a range of strategies that would have helped them during the crisis, including visible, consistent and empathetic leadership, adequate training and a supportive work environment. Conclusion: The context of the pandemic has highlighted the vulnerability of the psychological well‐being of early career nurses in the workforce. Immediate implementation of some of the more simple interventions suggested in this paper would provide early career nurses with rapid support. More complex support mechanisms should be given immediate consideration, with a view to implementation in the longer term. Implications for the Profession: This study contributes new knowledge about the psychological well‐being of early career nurses working during the pandemic and suggests support mechanisms that will be crucial for the retention of these nurses in the profession. A measurement of resilience may be useful for determining the appropriate level of support to provide to early career nurses. Impact: Early career nurses are vulnerable to attrition from the profession. This could be exacerbated if the psychological well‐being of these nurses is not being supported.Around 25% of early career nurses suffered from persistent symptoms of post‐traumatic stress disorder while working as nurses during the height of the pandemic, which is a novel finding compared to other longitudinal studies.Understanding the psychological well‐being of early career nurses working during a crisis period (such as a pandemic) equips nurse managers with appropriate strategies to improve nurses' emotional health and to enhance their retention within the workforce.The current findings may be of interest to clinical practitioners who have responsibility for the retention of nursing staff. No patient or public contribution. One of the authors is a statistician. [ABSTRACT FROM AUTHOR]

Objective: Myocardial infarction (MI) results in mental health consequences, including depression and post-traumatic stress disorder (PTSD). The risk and protective factors of such mental consequences are not fully understood. This study examined the relation between MI severity and future mental health consequences and the moderating role of vagal nerve activity. Methods: In a reanalysis of data from the Myocardial Infarction-Stress Prevention Intervention (MI-SPRINT) study, 154 post-MI patients participated. MI severity was measured by the Killip Scale and by troponin levels. Depression and PTSD symptoms were assessed with valid questionnaires, both at 3 and 12 months. Vagal nerve activity was indexed by the heart rate variability (HRV) parameter of the root-mean square of successive R-R differences (RMSSD). Following multivariate analyses, the association between MI severity and distress was examined in patients with low and high HRV (RMSSD = 30 ms). Results: In the full sample, the Killip index predicted post-MI distress only at 3 months, while troponin predicted distress at 3- and 12-months post-MI. However, HRV moderated the effects of the Killip classification; Killip significantly predicted symptoms of depression and PTSD at 3- and 12-months post-MI, but only in patients with low HRV. Such moderation was absent for troponin. Conclusion: MI severity (Killip classification) predicted post-MI depression and PTSD symptoms, but only in patients with low HRV, suggesting that the vagal nerve is a partial protective (moderating) factor in the relation between Killip score and post-MI distress. [ABSTRACT FROM AUTHOR]

Predicting treatment response can inform treatment decisions, expectations, and optimize use of mental health treatment resources. This study examined heart rate (HR), heart rate variability (HRV), and a modified Stroop task (mStroop) to predict post-traumatic stress disorder (PTSD) treatment response. We report on an observational, longitudinal study with 45 U.S. veterans in outpatient PTSD care, who had deployed to Iraq or Afghanistan. HR and HRV were collected before, during, and after virtual reality (VR) combat and civilian scenes. HRV recovery was defined as HRV after a 3-minute VR simulation minus HRV during a VR scene. mStroop threat variables included index scores for combat and general threat. Self-report data were collected at baseline and 6 months later. The outcome variable was the 17-item Clinician Administered PTSD Scale (CAPS). Controlling for baseline CAPS and number of combat experiences, the following baseline HRV recovery variables were significant predictors of 6-month CAPS: standard deviation of normal beat to beat interval (SDNN) after combat scene minus SDNN during combat scene and low-frequency (LF HRV) after civilian scene minus LF during civilian scene. HRV at rest, HR reactivity, HR recovery, and mStroop scores did not predict treatment response. In conclusion, HRV recovery variables in the context of a standardized VR stressor were significant predictors of PTSD treatment response after controlling for baseline CAPS and number of combat experiences. The direction of this relationship indicates that greater baseline HRV recovery predicts lower 6-month PTSD symptom severity. This was an exploratory study in need of replication. [ABSTRACT FROM AUTHOR]

Purpose: Public safety personnel (PSP) perform work that puts them at greater risk of psychological injury than the general public. PSP who subsequently develop posttraumatic stress disorder (PTSD) or other mental health conditions may need to take time off of work and use the workers compensation system. Very little is known about the experiences of PSP making this type of claim in Ontario to the Workplace Safety and Insurance Board (WSIB), or which healthcare professionals (HCP) PSP access as part of the treatment and return to work (RTW) process. This study captures the experiences of Ontario PSP in their RTW journeys, including with employers, WSIB, and HCPs. Methods: A survey-based study was conducted, using email and social media platforms to distribute the survey to PSP across Ontario. Quantitative data were summarized using means and frequencies, and open text results were analyzed using qualitative framework analysis. Results: 145 survey respondents met the inclusion criteria for the study. On a scale out of 5, PSP rated their experience with WSIB and employer support as poor on their first RTW attempt with an average rating of 2.93 and 2.46 respectively. The top three HCPs accessed by PSP were psychologists (61%), occupational therapists (OT; 60%) and general practitioners (GP; 44%). Respondents identified the cultural competence of HCPs in understanding their work demands and work culture as very important. Conclusions: To improve RTW experiences for PSP who make a workers compensation claim for a psychological injury, an increase in HCP cultural competence related to PSP work is indicated, as well as improved RTW processes and workplace support. [ABSTRACT FROM AUTHOR]

Chronic pain and post-traumatic stress disorder (PTSD) frequently co-occur, and research suggests that these 2 conditions exacerbate one another producing greater impact on normal functioning in combination than separately. The influence of traumatic experiences on both pain and PTSD has been shown, but the nature of this interplay remains unclear. Although Criterion A trauma is required for the diagnosis of PTSD, whether the association between PTSD and chronic pain is dependent on Criterion A is underexplored. In this observational cohort study, we examined the association between pain and PTSD-like symptoms in the context of Criterion A trauma in 5,791 men from the Vietnam Era Twin Registry. Correlations and mixed-effects regression models were used to evaluate the relationship between PTSD Checklist-Civilian Version symptoms and multiple indicators of pain from the Short Form McGill Pain Questionnaire across trauma history and chronic pain conditions. 53.21% of the participants experienced trauma consistent with DSM-IV Criterion A for PTSD. The associations between pain indicators and PTSD-like symptoms was stronger for individuals with a history of trauma but remained robust for individuals without trauma history. Small but significant interactions between past trauma and pain indicators and PTSD-like symptoms were observed. Findings were similar in a subsample of participants with history of chronic pain conditions. The relationship between PTSD-like symptoms and indicators of pain were largely independent of trauma consistent with Criterion A, highlighting the need to better understand and address stressful life events in chronic pain patients and pain concerns in individuals reporting trauma. PERSPECTIVE: This article demonstrates that the relationship between PTSD-like symptoms and indicators of pain is largely independent of trauma consistent with Criterion A. This finding highlights the need to better understand and address stressful life events in chronic pain patients and pain concerns in individuals reporting trauma.

ObjectiveHigh levels of psychological distress increase the risk of a wide range of medical diseases. In this study, we investigated the association between posttraumatic stress disorder (PTSD) and kidney disease.MethodsWorld Trade Center (WTC) responders were included if they had two or more measures of estimated glomerular filtration rate (eGFR). The PTSD Checklist (PCL) was used to define no PTSD (PCL < 40), "mild" PTSD (40 ≤ PCL

ObjectiveThe evaluation of memory complaints in mild traumatic brain injury (mTBI) remains an important clinical consideration, especially in the context of comorbid psychiatric symptoms such as posttraumatic stress disorder (PTSD). We compared subjective memory complaints in veterans with and without a history of mTBI, examined ratings between those with single versus multiple mTBIs, and investigated associations between memory complaints and PTSD symptom severity.Methods117 outpatient veterans (mTBI: n = 79 [single mTBI: n = 22, multiple mTBI: n = 57], military controls [MCs]: n = 38) completed a TBI history assessment, the Prospective-Retrospective Memory Questionnaire (PRMQ), and the PTSD Checklist-Military Version (PCL-M).ResultsHierarchical multiple regression showed that greater PCL-M scores significantly predicted elevated PRMQ-Total scores, accounting for 38% of the variance explained (P < .001). mTBI status predicted an additional 5% of variance in memory complaints (P < .01). The multiple-mTBI group endorsed more memory complaints than either MCs (P < .01) or the single-mTBI group (P < .05), who did not differ from MCs (P > .50).ConclusionsComorbid PTSD symptoms are an important factor when considering memory complaints in veterans with a reported history of mTBI. However, independent of comorbid PTSD symptoms, mTBI status-particularly in the context of repetitive neurotrauma-uniquely contributes to memory complaints. Findings suggest that veterans with a history of multiple mTBIs may be a particularly vulnerable group in need of specialized interventions and/or psychoeducation.

The human toll of disasters extends beyond death, injury and loss. Post-traumatic stress (PTS) can be common among directly exposed individuals, and children are particularly vulnerable. Even children far removed from harm's way report PTS, and media-based exposure may partially account for this phenomenon. In this study, we examine this issue using data from nearly 400 9- to 11-year-old children collected before and after Hurricane Irma, evaluating whether pre-existing neural patterns moderate associations between hurricane experiences and later PTS. The 'dose' of both self-reported objective exposure and media exposure predicted PTS, the latter even among children far from the hurricane. Furthermore, neural responses in brain regions associated with anxiety and stress conferred particular vulnerability. For example, heightened amygdala reactivity to fearful stimuli moderated the association between self-reported media exposure and PTS. Collectively, these findings show that for some youth with measurable vulnerability, consuming extensive disaster-related media may offer an alternative pathway to disaster exposure that transcends geography and objective risk.

ObjectivePatients with posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are often not offered exposure therapy for PTSD due to concerns that symptoms may worsen. This study examined whether initiating exposure would cause exacerbation of PTSD, alcohol use, depression, or suicidal ideation (SI) among patients with PTSD/AUD participating in exposure therapy for PTSD.MethodVeterans were randomized to either concurrent treatment of PTSD and substance use disorders using prolonged exposure (COPE) or seeking safety, a nonexposure intervention, and were included in this study if they had data to at least Session 5 available (n = 81). They completed measures of PTSD, alcohol use, and depression/SI symptom severity throughout treatment and posttreatment. The reliable exacerbation method examined the number of participants who demonstrated clinically meaningful symptom exacerbation from Sessions 3 to 5 (capturing the prepost window for the start of exposure in COPE). Hierarchical/logistic regressions examined whether treatment condition predicted exacerbation of symptoms. T tests/chi-square analyses examined whether clinical exacerbation led to worse posttreatment outcomes.ResultsFew participants endorsed exacerbation in symptoms of PTSD (15.8%), alcohol use (5.1%), depression (10.2%), or SI (12.8%). No significant treatment condition differences existed. Participants who experienced symptom exacerbation had higher rates of depression posttreatment compared to those who did not experience symptom exacerbation, but there were no differences in PTSD, alcohol use, or SI.ConclusionsExposure therapy did not lead to more clinical exacerbation than nonexposure therapy during the course of treatment, providing support that exposure therapy should not be withheld from patients with PTSD/AUD. This was a secondary analysis. and future studies that are sufficiently powered may demonstrate different results. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

BackgroundPosttraumatic stress disorder (PTSD) is associated with interpersonal dysfunction and adverse maternal health during the perinatal period (extending from conception through one year postpartum). However, PTSD is a heterogeneous disorder, and little is known about which aspects of this disorder may be particularly deleterious to the health of new mothers. Such data may inform more personalized approaches to PTSD prevention and treatment among postpartum women.MethodsUsing confirmatory factor analysis, we compared three models of PTSD symptom structure-the four-factor dysphoria model, four-factor emotional numbing model, and five-factor dysphoric arousal model-in 1,663 postpartum women from the Community and Child Health Network (CCHN). We examined associations between PTSD symptom dimensions of the best-fitting model with four correlates relevant to maternal health and functioning-parenting stress, partner relationship stress, relationship satisfaction, and contraceptive use.ResultsThough all models fit well, the five-factor dysphoric arousal model provided optimal fit. Symptom dimensions from this model-re-experiencing, avoidance, numbing, dysphoric arousal, and anxious arousal-evidenced differential associations with the maternal health indicators. Numbing symptoms were most strongly associated with indicators of poor interpersonal functioning, whereas dysphoric arousal symptoms were most strongly related to low-efficacy contraceptive use.LimitationsOur cross-sectional study assessed DSM-IV PTSD symptoms.ConclusionsPTSD symptoms among postpartum women are best-represented by five factors. Numbing symptoms (e.g., restricted affect, detachment) are most strongly associated with interpersonal difficulties, whereas dysphoric arousal symptoms (e.g., agitation, irritability) are linked with low-efficacy contraceptive use. Screening for these symptoms may help promote the health of new mothers.

IntroductionLittle is known about the relationship between moral distress and mental health problems. We examined moral distress in 2579 frontline healthcare workers (FHCWs) caring for coronavirus disease 2019 (COVID-19) patients during the height of the spring 2020 pandemic surge in New York City. The goals of the study were to identify common dimensions of COVID-19 moral distress; and to examine the relationship between moral distress, and positive screen for COVID-19-related posttraumatic stress disorder (PTSD) symptoms, burnout, and work and interpersonal functional difficulties.MethodData were collected in spring 2020, through an anonymous survey delivered to a purposively-selected sample of 6026 FHCWs at Mount Sinai Hospital; 2579 endorsed treating COVID-19 patients and provided complete survey responses. Physicians, house staff, nurses, physician assistants, social workers, chaplains, and clinical dietitians comprised the sample.ResultsThe majority of the sample (52.7%-87.8%) endorsed moral distress. Factor analyses revealed three dimensions of COVID-19 moral distress: negative impact on family, fear of infecting others, and work-related concerns. All three factors were significantly associated with severity and positive screen for COVID-19-related PTSD symptoms, burnout, and work and interpersonal difficulties. Relative importance analyses revealed that concerns about work competencies and personal relationships were most strongly related to all outcomes.ConclusionMoral distress is prevalent in FHCWs and includes family-, infection-, and work-related concerns. Prevention and treatment efforts to address moral distress during the acute phase of potentially morally injurious events may help mitigate risk for PTSD, burnout, and functional difficulties.

BackgroundThe coronavirus-2019 (COVID-19) pandemic is associated with increased potential for morally injurious events, during which individuals may experience, witness, or learn about situations that violate deeply held moral beliefs. However, it is unknown how pandemic risk and resilience factors are associated with COVID-related moral injury.MethodsIndividuals residing in the U.S. (N = 839; Mage = 37.09, SD = 11.06; 78% women; 63% White; 33% PTSD) participating in an online survey reported on COVID-19 related moral injury (modified Moral Injury Events Scale), perceived current and future threat of pandemic on life domains (social, financial, health), and COVID-19 risky and protective behaviors. Multivariate linear regressions examined associations of perceived threat and risky and protective behaviors on type of COVID-19 related moral injury (betrayal, transgression by others, self).ResultsParticipants endorsed MI betrayal (57%, N = 482), transgression by other (59%, N = 497), and by self 17% (N = 145). Adjusting for sociodemographics, only future threat of COVID-19 to health was significantly associated with betrayal (B = 0.21, p = .001) and transgression by other (B = 0.16, p = .01), but not by self. In contrast, high frequency of risky behaviors was associated with transgressions by self (B = 0.23, p

BackgroundPosttraumatic stress disorder (PTSD) has been associated with increased cardiovascular risk, however, underlying mechanisms have not been fully specified. PTSD is associated with stress-related hormones, including dysregulated glucocorticoid activity. Dysregulation of aldosterone, a mineralocorticoid activated by psychological stress and implicated in cardiovascular damage, may be a relevant pathway linking PTSD and cardiovascular risk. Few studies to date have evaluated the association between PTSD and aldosterone, none with repeated measures of aldosterone. We examined if trauma and PTSD were associated with altered aldosterone levels relative to women unexposed to trauma.MethodsThe association of trauma exposure and chronic PTSD with plasma aldosterone levels was investigated in 521 middle-aged women in the Nurses' Health Study II. Aldosterone was assessed at two time points, 10-16 years apart, and trauma exposure and PTSD were also ascertained for both time points. Regarding exposure assessment, women were characterized based on a structured diagnostic interview as: having chronic PTSD (PTSD at both time points; n = 174); being trauma-exposed (trauma exposure at first time point but no PTSD; n = 174); and being unexposed (no trauma exposure at either time point; reference group for all analyses; n = 173). Linear mixed models examined associations of trauma and PTSD status with log-transformed aldosterone levels, adjusting for covariates and health-related variables that may confound or lie on the pathway between PTSD and altered aldosterone levels.ResultsAcross the sample, mean aldosterone concentration decreased over time. Adjusting for covariates, women with chronic PTSD had significantly lower aldosterone levels averaged over time, compared to women unexposed to trauma (β = - 0.08, p = 0.04). Interactions between trauma/PTSD group and time were not significant, indicating change in aldosterone over time did not differ by trauma/PTSD status. Post-hoc exploratory analyses suggested that menopausal status partially mediated the relationship between chronic PTSD status and aldosterone level, such that postmenopausal status explained 7% of the effect of PTSD on aldosterone.ConclusionsThese findings indicate that PTSD is associated with lower levels of aldosterone. Further work is needed to understand implications of this type of dysregulation in a key biological stress system for cardiovascular and other health outcomes previously linked with PTSD.

While the BDNF Val66Met polymorphism has been linked to various trauma and anxiety - related psychiatric disorders, limited focus has been on the neural structures that might modulate its relationship with objective measures of threat sensitivity. Therefore, we assessed whether there was an interaction of Val66Met polymorphism with brain area volumes previously associated with anxiety and PTSD, such as the ventromedial prefrontal cortex (vmPFC), insular cortex (IC), and dorsal and ventral anterior cingulate cortices (dACC and vACC), in predicting fear-potentiated psychophysiological response in a clinical sample of Veterans. 110 participants engaged in a fear-potentiated acoustic startle paradigm and provided genetic and imaging data. Fear conditions included no, ambiguous, and high threat conditions (shock). Psychophysiological response measures included electromyogram (EMG), skin conductance response (SCR), and heart rate (HR). PTSD status, trauma history, and demographics were also assessed. There was an interaction of Met allele carrier status with vmPFC, IC, dACC, and vACC volumes for predicting SCR (p

Posttraumatic stress disorder (PTSD) is associated with lower gray matter volume (GMV) in brain regions critical for extinction of learned threat. However, relationships among volume, extinction learning, and PTSD symptom development remain unclear. We investigated subcortical brain volumes in regions supporting extinction learning and fear-potentiated startle (FPS) to understand brain-behavior interactions that may impact PTSD symptom development in recently traumatized individuals. Participants (N = 99) completed magnetic resonance imaging and threat conditioning two weeks following trauma exposure as part of a multisite observational study to understand the neuropsychiatric effects of trauma (AURORA Study). Participants completed self-assessments of PTSD (PTSD Checklist for DSM-5; PCL-5), dissociation, and depression symptoms two- and eight-weeks post-trauma. We completed multiple regressions to investigate relationships between FPS during late extinction, GMV, and PTSD symptom development. The interaction between thalamic GMV and FPS during late extinction at two weeks post-trauma predicted PCL-5 scores eight weeks (t (75) = 2.49, β = 0.28, p = 0.015) post-trauma. Higher FPS predicted higher PCL-5 scores in the setting of increased thalamic GMV. Meanwhile, lower FPS also predicted higher PCL-5 scores in the setting of decreased thalamic GMV. Thalamic GMV and FPS interactions also predicted posttraumatic dissociative and depressive symptoms. Amygdala and hippocampus GMV by FPS interactions were not associated with posttraumatic symptom development. Taken together, thalamic GMV and FPS during late extinction interact to contribute to adverse posttraumatic neuropsychiatric outcomes. Multimodal assessments soon after trauma have the potential to distinguish key phenotypes vulnerable to posttraumatic neuropsychiatric outcomes.

Active-duty Army personnel can be exposed to traumatic warzone events and are at increased risk for developing post-traumatic stress disorder (PTSD) compared with the general population. PTSD is associated with high individual and societal costs, but identification of predictive markers to determine deployment readiness and risk mitigation strategies is not well understood. This prospective longitudinal naturalistic cohort study-the Fort Campbell Cohort study-examined the value of using a large multidimensional dataset collected from soldiers prior to deployment to Afghanistan for predicting post-deployment PTSD status. The dataset consisted of polygenic, epigenetic, metabolomic, endocrine, inflammatory and routine clinical lab markers, computerized neurocognitive testing, and symptom self-reports. The analysis was computed on active-duty Army personnel (N = 473) of the 101st Airborne at Fort Campbell, Kentucky. Machine-learning models predicted provisional PTSD diagnosis 90-180 days post deployment (random forest: AUC = 0.78, 95% CI = 0.67-0.89, sensitivity = 0.78, specificity = 0.71; SVM: AUC = 0.88, 95% CI = 0.78-0.98, sensitivity = 0.89, specificity = 0.79) and longitudinal PTSD symptom trajectories identified with latent growth mixture modeling (random forest: AUC = 0.85, 95% CI = 0.75-0.96, sensitivity = 0.88, specificity = 0.69; SVM: AUC = 0.87, 95% CI = 0.79-0.96, sensitivity = 0.80, specificity = 0.85). Among the highest-ranked predictive features were pre-deployment sleep quality, anxiety, depression, sustained attention, and cognitive flexibility. Blood-based biomarkers including metabolites, epigenomic, immune, inflammatory, and liver function markers complemented the most important predictors. The clinical prediction of post-deployment symptom trajectories and provisional PTSD diagnosis based on pre-deployment data achieved high discriminatory power. The predictive models may be used to determine deployment readiness and to determine novel pre-deployment interventions to mitigate the risk for deployment-related PTSD.

IntroductionThe ongoing coronavirus disease 2019 (COVID-19) pandemic is a globally significant crisis with a rapid spread worldwide, high rates of illness and mortality, a high degree of uncertainty, and a disruption of daily life across the sociodemographic spectrum. The clinically relevant psychological consequences of this catastrophe will be long-lasting and far-reaching. There is an emerging body of empirical literature related to the mental health aspects of this pandemic and this body will likely expand exponentially. The COVID-19 pandemic is an example of a historic catastrophe from which we can learn much and from which the field will need to archive, interpret, and synthesize a multitude of clinical and research observations.MethodsIn this commentary, we discuss situations and contexts in which a diagnosis of posttraumatic stress disorder (PTSD) may or may not apply within the context of diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) criteria.ResultsOur consensus is that a COVID-related event cannot be considered traumatic unless key aspects of DSM-5's PTSD Criterion A have been established for a specific type of COVID-19 event (e.g., acute, life-threatening, and catastrophic).ConclusionThe application of a more liberal interpretation of Criterion A will dilute the PTSD diagnosis, increase heterogeneity, confound case-control research, and create an overall sample pool with varying degrees of risk and vulnerability factors.

Traumatic events and ensuing stress are not widely studied in individuals with severe mental illness (SMI) despite their increased vulnerability to both. Far less is known about traumatic events and posttrauma reactions in people with SMI in low-resourced settings.ObjectiveTo address this gap in knowledge, our study focused on trauma and its effects for individuals with SMI and their caregivers in rural Ethiopia. Study aims were to identify events that were considered traumatic by stakeholders; characterize the mental health effects of such events; and discern events and posttrauma symptoms most relevant for SMI.MethodQualitative interviews were gathered from 48 participants in Ethiopia who included individuals with SMI, their caregivers, health care providers, and community and religious leaders.ResultsBased on a combined emic and etic approach, major traumatic events included those commonly experienced in rural Ethiopia (e.g., lost property, forced marriage) and endorsed by individuals with SMI (e.g., restraining or chaining, SMI illness in a low-resourced setting). In addition, traumatic events were identified consistent with Western medical criteria (e.g., physical assault, sexual assault). Posttrauma symptoms that were commonly reported included emotions like anger and sadness; thinking too much; crying; and somatic (e.g., burning sensation) and physiological (e.g., shortness of breath) symptoms. As for symptoms consistent with the Diagnostic and Statistical Manual, we found the presence of all four symptom clusters.ConclusionsOverall, results point to the common occurrence of traumatic events and trauma-linked symptoms for individuals with SMI and their caregivers, including as a result of SMI. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

UNLABELLED: Post-Traumatic Stress Disorder (PTSD) is a psychiatric condition resulting from threatening or horrifying events. We hypothesized that circadian rhythm changes, measured by a wrist-worn research watch are predictive of post-trauma outcomes. APPROACH: 1618 post-trauma patients were enrolled after admission to emergency departments (ED). Three standardized questionnaires were administered at week eight to measure post-trauma outcomes related to PTSD, sleep disturbance, and pain interference with daily life. Pulse activity and movement data were captured from a research watch for eight weeks. Standard and novel movement and cardiovascular metrics that reflect circadian rhythms were derived using this data. These features were used to train different classifiers to predict the three outcomes derived from week-eight surveys. Clinical surveys administered at ED were also used as features in the baseline models. RESULTS: The highest cross-validated performance of research watch-based features was achieved for classifying participants with pain interference by a logistic regression model, with an area under the receiver operating characteristic curve (AUC) of 0.70. The ED survey-based model achieved an AUC of 0.77, and the fusion of research watch and ED survey metrics improved the AUC to 0.79. SIGNIFICANCE: This work represents the first attempt to predict and classify post-trauma symptoms from passive wearable data using machine learning approaches that leverage the circadian desynchrony in a potential PTSD population.

Anger is a common and debilitating symptom of post-traumatic stress disorder (PTSD). Although studies have identified brain circuits underlying anger experience and expression in healthy individuals, how these circuits interact with trauma remains unclear. Here, we performed the first study examining the neural correlates of anger in patients with PTSD. Using a data-driven approach with resting-state fMRI, we identified two prefrontal regions whose overall functional connectivity was inversely associated with anger: the left anterior middle frontal gyrus (aMFG) and the right orbitofrontal cortex (OFC). We then used concurrent TMS-EEG to target the left aMFG parcel previously identified through fMRI, measuring its cortical excitability and causal connectivity to downstream areas. We found that low-anger PTSD patients exhibited enhanced excitability in the left aMFG and enhanced causal connectivity between this region and visual areas. Together, our results suggest that left aMFG activity may confer protection against the development of anger, and therefore may be an intriguing target for circuit-based interventions for anger in PTSD.

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.

Emotion processing abnormalities and sleep pathology are central to the phenomenology of paediatric posttraumatic stress disorder, and sleep disturbance has been linked to the development, maintenance and severity of the disorder. Given emerging evidence indicating a role for sleep in emotional brain function, it has been proposed that dysfunctional processing of emotional experiences during sleep may play a significant role in affective disorders, including posttraumatic stress disorder. Here we sought to examine the relationship between sleep and emotion processing in typically developing youth, and youth with a diagnosis of posttraumatic stress disorder . We use high-density electroencephalogram to compare baseline sleep with sleep following performance on a task designed to assess both memory for and reactivity to negative and neutral imagery in 10 youths with posttraumatic stress disorder, and 10 age- and sex-matched non-traumatized typically developing youths. Subjective ratings of arousal to negative imagery (ΔArousal = post-sleep minus pre-sleep arousal ratings) remain unchanged in youth with posttraumatic stress disorder following sleep (mean increase 0.15, CI -0.28 to +0.58), but decreased in TD youth (mean decrease -1.0, 95% CI -1.44 to -0.58). ΔArousal, or affective habituation, was negatively correlated with global change in slow-wave activity power (ρ = -0.58, p = .008). When considered topographically, the correlation between Δslow-wave activity power and affective habituation was most significant in a frontal cluster of 27 electrodes (Spearman, ρ = -0.51, p = .021). Our results highlight the importance of slow-wave sleep for adaptive emotional processing in youth, and have implications for symptom persistence in paediatric posttraumatic stress disorder. Impairments in slow-wave activity may represent a modifiable risk factor in paediatric posttraumatic stress disorder.

Post-traumatic stress disorder (PTSD) leads to impairments in both cognitive and affective functioning. Animal work suggests that chronic stress reduces dopamine tone, and both animal and human studies argue that changes in dopamine tone influence working memory, a core executive function. These findings give rise to the hypothesis that increasing cortical dopamine tone in individuals with greater PTSD symptomatology should improve working memory performance. In this pharmacological functional magnetic resonance imaging (fMRI) study, 30 US military veterans exhibiting a range of PTSD severity completed an emotional working memory task. Each subject received both placebo and the catechol-O-methyl transferase inhibitor tolcapone, which increases cortical dopamine tone, in randomized, double-blind, counterbalanced fashion. Mnemonic discriminability (calculated with d', an index of the detectability of working memory signals) and response bias were evaluated in the context of task-related brain activations. Subjects with more severe PTSD showed both greater tolcapone-mediated improvements in d' and larger tolcapone-mediated reductions in liberally-biased responding for fearful stimuli. FMRI revealed that tolcapone augmented activity within bilateral frontoparietal control regions during the decision phase of the task. Specifically, tolcapone increased cortical responses to fearful relative to neutral stimuli in higher severity PTSD subjects, and reduced cortical responses to fearful stimuli for lower severity PTSD subjects. Moreover, tolcapone modulated prefrontal connectivity with areas overlapping the default mode network. These findings suggest that enhancing cortical dopamine tone may represent an approach to remediating cognitive and affective dysfunction in individuals with more severe PTSD symptoms.

This is the initial report of results from the AURORA multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. We focus on n = 666 participants presenting to EDs following a motor vehicle collision (MVC) and examine associations of participant socio-demographic and participant-reported MVC characteristics with 8-week posttraumatic stress disorder (PTSD) adjusting for pre-MVC PTSD and mediated by peritraumatic symptoms and 2-week acute stress disorder (ASD). Peritraumatic Symptoms, ASD, and PTSD were assessed with self-report scales. Eight-week PTSD prevalence was relatively high (42.0%) and positively associated with participant sex (female), low socioeconomic status (education and income), and several self-report indicators of MVC severity. Most of these associations were entirely mediated by peritraumatic symptoms and, to a lesser degree, ASD, suggesting that the first 2 weeks after trauma may be a uniquely important time period for intervening to prevent and reduce risk of PTSD. This observation, coupled with substantial variation in the relative strength of mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated with more in-depth analyses of the rich and evolving AURORA data.

BackgroundPsychiatric comorbidities may complicate depression treatment by being associated with increased role impairments. However, depression symptom severity might account for these associations. Understanding the independent associations of depression severity and comorbidity with impairments could help in treatment planning. This is especially true for depressed Veterans, who have high psychiatric comorbidity rates.Methods2,610 Veterans beginning major depression treatment at the Veterans Health Administration (VHA) were administered a baseline self-report survey that screened for diverse psychiatric comorbidities and assessed depression severity and role impairments. Logistic and generalized linear regression models estimated univariable and multivariable associations of depression severity and comorbidities with impairments. Population attributable risk proportions (PARPs) estimated the relative importance of depression severity and comorbidities in accounting for role impairments.ResultsNearly all patients (97.8%) screened positive for at least one comorbidity and half (49.8%) for 4+ comorbidities. The most common positive screens were for generalized anxiety disorder (80.2%), posttraumatic stress disorder (77.9%), and panic/phobia (77.4%). Depression severity and comorbidities were significantly and additively associated with impairments in multivariable models. Associations were attenuated much less for depression severity than for comorbidities in multivariable versus univariable models. PARPs indicated that 15-60% of role impairments were attributable to depression severity and 5-32% to comorbidities.LimitationsThe screening scales could have over-estimated comorbidity prevalence. The cross-sectional observational design cannot determine either temporal or causal priorities.ConclusionsAlthough positive screens for psychiatric comorbidity are pervasive among depressed VHA patients, depression severity accounts for most of the associations of these comorbidities with role impairments.

Neuropsychiatric symptoms are common, comorbid, and often disabling for patients with traumatic brain injury (TBI). Identifying transdiagnostic symptom dimensions post-TBI may help overcome limitations of traditional psychiatric diagnoses and advance treatment development. We characterized the dimensional structure of neuropsychiatric symptoms at 2-weeks postinjury in n = 1,732 TBI patients and n = 238 orthopedic-injured trauma controls (OTC) from the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Symptoms were reported on the Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, PTSD Checklist for DSM-5, PROMIS Pain Intensity scale, and Insomnia Severity Index. We established a novel factor model of neuropsychiatric symptoms and evaluated how 3 TBI severity strata and OTC patients differed in symptom severity. The final factor model had 6 first-order factors subsumed by 2 second-order factors: Internalizing (encompassing Depression, Anxiety, and Fear) and Somatic symptoms (Sleep, Physical, Pain). Somatic symptoms fit better as a correlated factor of (vs. a lower-order factor within) Internalizing. All symptom dimensions except for Pain were more severe in 1 or more TBI subgroups, as compared to the OTC group. Milder brain injury was generally associated with more severe symptoms, whereas more general injury severity (higher level of care, e.g., emergency department, intensive care unit) was associated with more pain. The findings indicate a broad factor resembling the internalizing factor of general psychopathology in traumatically injured patients, alongside a distinct somatic symptom factor. Brain injury, especially milder brain injury, may exacerbate liabilities toward these symptoms. These neuropsychiatric dimensions may help advance more precision medicine research for TBI. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

During the COVID-19 pandemic, social distancing measures often result in individual isolation, which can lead to adverse mental outcomes. We collected online questionnaires from 3,952 US adults to examine the impact of "shelter-in-place" guidelines on mental health, and to explore potential disparities and modifiable factors. Self-reported anxiety, depression, and PTSD symptoms were associated with more restrictive quarantine. Younger adults, women, those with lower income, more insecurity, more media exposure, reduced physical activity, or worsened family relationships were particularly affected. Targeted prevention on susceptible subpopulations, including young adults and lower SES groups, might help mitigate disparities in COVID-19-related mental health problems.

Study objectiveAmong a comprehensive range of frontline emergency department health care personnel, we assessed symptoms of anxiety and burnout, specific coronavirus disease 2019 (COVID-19) work-related stressors, and risk for post-traumatic stress disorder (PTSD). We also determined whether COVID-19 serologic testing of HCP decreased their self-reported anxiety.MethodsIn a prospective cohort study from May 13, 2020, to July 8, 2020, we used electronic surveys to capture participant self-reported symptoms before and after serologic testing for anti-SARS-CoV-2 immunoglobulin G antibodies. Participants were physicians, nurses, advanced practice providers, and nonclinical ED personnel at 20 geographically diverse United States EDs. We evaluated these domains: 1) the effects of the COVID-19 pandemic on overall stress and anxiety; 2) COVID-19-related work stressors; 3) burnout; and 4) PTSD risk (measured using the Primary Care-PTSD Screen for DSM-5, a 5-item screening instrument in which a score of ≥3 signifies high risk for PTSD). We also assessed perceptions of whether results of COVID-19 antibody testing decreased participants' self-reported anxiety.ResultsOf 1,606 participants, 100% and 88% responded to the baseline and follow-up surveys, respectively. At baseline, approximately half (46%) reported symptoms of emotional exhaustion and burnout from their work, and 308 (19.2%, 95% confidence interval [CI] 17.3% to 21.1%) respondents screened positive for increased PTSD risk. Female respondents were more likely than males to screen positive (odds ratio [OR] 2.03, 95% CI 1.49 to 2.78). Common concerns included exposing their family and the health of coworkers diagnosed with COVID-19. After receiving antibody test results, 54% (95% CI 51.8 to 56.7) somewhat agreed, agreed, or strongly agreed that knowledge of their immune status had decreased their anxiety. A positive serology result indicating prior SARS-CoV-2 infection was associated with a higher likelihood of reporting decreased anxiety (2.83, 95% CI 1.37 to 5.83).ConclusionSymptoms of anxiety and burnout were prevalent across the spectrum of ED staff during the COVID-19 pandemic. One-fifth of ED personnel appeared to be at risk for PTSD. Increased provision of serologic testing may help to mitigate anxiety.

Neurobiological markers of future susceptibility to posttraumatic stress disorder (PTSD) may facilitate identification of vulnerable individuals in the early aftermath of trauma. Variability in resting-state networks (RSNs), patterns of intrinsic functional connectivity across the brain, has previously been linked to PTSD, and may thus be informative of PTSD susceptibility. The present data are part of an initial analysis from the AURORA study, a longitudinal, multisite study of adverse neuropsychiatric sequalae. Magnetic resonance imaging (MRI) data from 109 recently (i.e., ~2 weeks) traumatized individuals were collected and PTSD and depression symptoms were assessed at 3 months post trauma. We assessed commonly reported RSNs including the default mode network (DMN), central executive network (CEN), and salience network (SN). We also identified a proposed arousal network (AN) composed of a priori brain regions important for PTSD: the amygdala, hippocampus, mamillary bodies, midbrain, and pons. Primary analyses assessed whether variability in functional connectivity at the 2-week imaging timepoint predicted 3-month PTSD symptom severity. Left dorsolateral prefrontal cortex (DLPFC) to AN connectivity at 2 weeks post trauma was negatively related to 3-month PTSD symptoms. Further, right inferior temporal gyrus (ITG) to DMN connectivity was positively related to 3-month PTSD symptoms. Both DLPFC-AN and ITG-DMN connectivity also predicted depression symptoms at 3 months. Our results suggest that, following trauma exposure, acutely assessed variability in RSN connectivity was associated with PTSD symptom severity approximately two and a half months later. However, these patterns may reflect general susceptibility to posttraumatic dysfunction as the imaging patterns were not linked to specific disorder symptoms, at least in the subacute/early chronic phase. The present data suggest that assessment of RSNs in the early aftermath of trauma may be informative of susceptibility to posttraumatic dysfunction, with future work needed to understand neural markers of long-term (e.g., 12 months post trauma) dysfunction. Furthermore, these findings are consistent with neural models suggesting that decreased top-down cortico-limbic regulation and increased network-mediated fear generalization may contribute to ongoing dysfunction in the aftermath of trauma.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P

Introduction: Over the last five years in India, there has been a three-fold increase in the number of candidates taking the Foreign Medical Graduate Examination (FMGE). Foreign Medical Graduates (FMGs) have recently experienced the Coronavirus Disease-2019 (COVID-19) pandemic and wars/internal conflicts in the countries where they study. Aim: To assess the mental health status of FMGs and analyse the associated socio-demographic, economic, and academic factors, as well as the impact of COVID-19 on their mental health. Materials and Methods: This explanatory mixed-method study utilised a quantitative method (Phase 1 - Self-administered questionnaire GHQ-12) followed by a qualitative method {Phase 2 - Focus Group Discussion (FGD)}. The study included 169 FMGs doing their internship (academic year 2022-23) at Government Medical College Krishnagiri, Tamil Nadu, India, and their colleagues/batchmates who were willing to participate in the study. Descriptive statistics and student t-test were used to analyse the variables. Results: In the present study, 99 (58.6%) study participants were male, 130 (76.9%) were in the age group of 23-25 years, and 114 (67.5%) belonged to the upper socio-economic class. About 80 (47.3%) respondents scored higher than the overall mean GHQ-12 score, indicating mental distress. FMGs who had not yet joined the internship reported significant mental health issues compared to those currently in internship. FGD participants felt a lack of confidence in patient care, academic burden, financial burden, family bereavement, and personal health issues were the impacts of the COVID-19 pandemic on their mental health. Conclusion: Almost half of the FMGs in the present study were under stress, which could be attributed to the financial burden in the family, lack of academic confidence, and personal loss during the COVID-19 pandemic.

Abstract Background Nurses are particularly at risk of suffering from post-traumatic stress disorder (PTSD) owing to their overwhelming workload, risk of infection, and lack of knowledge about the coronavirus disease 2019 (COVID-19). PTSD negatively affects an individual’s health, work performance, and patient safety. This study aims to assess factors related to PTSD among nurses after providing direct care to COVID-19 patients. Methods This study is a secondary analysis aimed at identifying factors influencing PTSD among nurses who provided direct care to COVID-19 patients. Data from 168 nurses, collected between October and November 2020, were analyzed. The independent variables were personal, interpersonal, and organizational and COVID-19-related factors (experience of quarantine and direct care of COVID-19 patients), and the dependent variables were PTSD symptoms evaluated based on the PTSD Checklist-5. The nurses’ experience of direct care for COVID-19 patients in the designated COVID-19 isolation wards during the first wave of the pandemic (February 2020 to May 2020) was included. Results Among the nurses, 18.5% exhibited symptoms of PTSD. When providing direct care to a patient in the designated COVID-19 isolation ward, nurses witnessing the death of a patient (p = .001), low level of nurse staffing (p = .008), and inconvenience of electronic health records programs (p = .034) were associated with PTSD symptoms. The experience of quarantine owing to COVID-19 was also associated with PTSD symptoms (p = .034). Additionally, the higher the nurse managers’ ability, leadership, and support of nurses in the current ward, the higher the possibility of lowering nurses’ PTSD symptoms (p = .006). Conclusions Governments and hospitals should prepare and implement organizational intervention programs to improve nurse managers’ leadership, nurse staffing levels, and electronic health records programs. Additionally, because nurses who have witnessed the death of a COVID-19 patient or are self-isolating are vulnerable to PTSD, psychological support should be provided.

IntroductionBoth trauma exposure and post-traumatic stress disorder (PTSD) are associated with increased risk of cardiovascular disease (CVD), the leading cause of death in the USA. Endothelial dysfunction, a modifiable, early marker of CVD risk, may represent a physiological mechanism underlying this association. This mechanism-focused cohort study aims to investigate the relationship between PTSD (both in terms of diagnosis and underlying symptom dimensions) and endothelial dysfunction in a diverse, community-based sample of adult men and women.Methods and analysisUsing a cohort design, 160 trauma-exposed participants without a history of CVD are designated to the PTSD group (n=80) or trauma-exposed matched control group (n=80) after a baseline diagnostic interview assessment. Participants in the PTSD group have a current (past month) diagnosis of PTSD, whereas those in the control group have a history of trauma but no current or past psychiatric diagnoses. Endothelial dysfunction is assessed via flow-mediated vasodilation of the brachial artery and circulating levels of endothelial cell-derived microparticles. Two higher order symptom dimensions of PTSD-fear and dysphoria-are measured objectively with a fear conditioning paradigm and attention allocation task, respectively. Autonomic imbalance, inflammation, and oxidative stress are additionally assessed and will be examined as potential pathway variables linking PTSD and its dimensions with endothelial dysfunction. Participants are invited to return for a 2-year follow-up visit to reassess PTSD and its dimensions and endothelial dysfunction in order to investigate longitudinal associations.Ethics and disseminationThis study is conducted in compliance with the Helsinki Declaration and University of California, Los Angeles Institutional Review Board. The results of this study will be disseminated via articles in peer-reviewed journals and presentations at academic conferences and to community partners.Trial registration numberNCT03778307; pre-results.

Obesity, binge-eating symptoms, and PTSD symptoms commonly co-occur. Avoidance, a key feature of PTSD and proposed mechanism of binge-eating, is one potential mechanism for explaining this clinical overlap. The purpose of the current study was to: 1) examine the associations between PTSD symptoms (PTSD Checklist-Civilian; PCL-C) and measures of bingeeating symptoms (Binge Eating Scale; BES) and obesity-related quality of life (Obesity Related Well-Being Questionnaire-97; ORWELL-97) in a sample of veterans with overweight or obesity (N = 89), and 2) determine whether experiential avoidance (The Acceptance and Action Questionnaire-II; AAQ-II) explains the relationship between PTSD symptoms and binge-eating symptoms, and PTSD symptoms and obesity-related quality of life, respectively. Scores on the PCL-C, BES, ORWELL-97, and AAQ-II were all significantly correlated. Linear regression analyses indicated that higher PCL-C scores were related to higher scores on the BES and ORWELL-97 after controlling for potentially confounding factors (BMI and race). Effect sizes were in the medium-large range. Further, AAQ-II mediated the relationship between PCL-C and ORWELL-97, but did not mediate the relationship between PCL-C and BES. These findings suggest that experiential avoidance should be considered in interventions addressing co-occurring PTSD, binge-eating, and poor obesity-related well-being. Longitudinal research is needed to better understand directionality of these relationships and changes over time.

In light of the well-established relationship between posttraumatic stress disorder (PTSD) and suicidal ideation (SI), there has been a push for treatments that simultaneously improve symptoms of PTSD and decrease SI. Using data from a randomized controlled hybrid implementation-effectiveness trial, the current study investigated the effectiveness of Cognitive Processing Therapy (CPT; Resick, Monson, & Chard, 2016) on PTSD and SI. The patient sample (N = 188) was diverse in military and veteran status, gender, and comorbidity, and 73% of the sample endorsed SI at one or more points during CPT. Participants demonstrated significant improvement in SI over the course of CPT. Multilevel growth curve modeling revealed a significant association between PTSD symptom change and change in SI. Results from cross-lagged multilevel regressions indicated that PTSD symptoms predicted SI in the next session, yet SI in a given session did not predict PTSD symptoms in the next session. Potentially relevant clinical factors (i.e., military status, gender, depression diagnosis, baseline SI, study consultation condition) were not associated with the relationship between PTSD symptoms and SI. These results add to the burgeoning literature suggesting that evidence-based treatments for PTSD, like CPT, reduce suicidality in a range of individuals with PTSD, and that this reduction is predicted by improvements in PTSD symptoms.

Comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) is common, defined by greater severity and impairment than either disorder alone, and associated with poor treatment attendance. Exposure therapies are effective in treating PTSD+AUD, yet substance use is still cited as a potential contraindication for exposure. This study examined substance use-related predictors of session attendance among veterans (N = 119) randomized to receive integrated exposure therapy (Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure [COPE]; Back et al., 2015) or integrated coping skills therapy (Seeking Safety [SS]; Najavits, 2002) in a clinical trial for comorbid PTSD+AUD (Norman et al., 2019). At baseline, greater percentage of heavy drinking days (β = -0.23, p = .011) and greater AUD severity per structured clinical interview for DSM-IV-TR (β = -0.21, p = .019) predicted fewer sessions across both treatments. Treatment type did not moderate the relationship between predictors and attendance, except for a trend for craving (p = .057), where greater craving predicted fewer sessions in SS (β = -0.31, p = .02) but not COPE (β = 0.14, p = .28). Percentage of abstinence days, AUD duration, and living in a controlled environment (e.g., recovery home) at the start of therapy were not associated with attendance in either treatment condition. Only a subset of substance use characteristics predicted attendance. Findings did not support the notion that alcohol use leads to lower attendance in exposure therapy compared to nonexposure therapy.

Inflammatory markers like C-reactive protein (CRP) have been associated with post-traumatic stress disorder (PTSD) and traumatic experiences, but the underlying mechanisms are unclear. We investigated the relationship among serum CRP, PTSD, and traits related to traumatic events and social support using genetic association data from the Psychiatric Genomics Consortium (23,185 PTSD cases and 151,309 controls), the UK Biobank (UKB; up to 117,900 individuals), and the CHARGE study (Cohorts for Heart and Aging Research in Genomic Epidemiology, 148,164 individual). Linkage disequilibrium score regression, polygenic risk scoring, and two-sample Mendelian randomization (MR) analyses were used to investigate genetic overlap and causal relationships. Genetic correlations of CRP were observed with PTSD (rg = 0.16, p = 0.026) and traits related to traumatic events, and the presence of social support (-0.28

People of color in the United States disproportionately bear the burden of trauma and posttraumatic stress disorder (PTSD). Pregnant women of color are at particular risk, as perinatal PTSD is associated with adverse maternal and child health. However, PTSD is a heterogeneous disorder comprising discrete symptom dimensions. Adopting a dimensional understanding of PTSD could aid in identifying women at-risk for the consequences of posttraumatic psychopathology and guide treatment selection. In a large sample of Latina, Black, and non-Hispanic White postpartum women in the United States (N = 1663), we examined racial and ethnic differences in the factors of the dysphoric arousal model-a leading dimensional model of PTSD. This model is characterized by five symptom dimensions: re-experiencing, avoidance, numbing, dysphoric arousal, and anxious arousal. Past-year trauma in this sample was common, afflicting nearly 70% of women. In unadjusted models, women of color exhibited more severe PTSD symptom levels across dimensions except for dysphoric arousal, with Black mothers particularly affected. In models adjusted for age, education, and poverty, Black women continued to report elevated symptoms of avoidance and, relative to Latina mothers, re-experiencing symptoms. In contrast, White women reported more dysphoric arousal symptoms relative to women of color. Illuminating differential patterns of symptom dimensions across racial and ethnic groups is critical to PTSD assessment and treatment and may shed light on disparities. Perinatal healthcare may be an important opportunity for posttraumatic symptom screening, and greater understanding of racial and ethnic variation in posttraumatic symptom dimensions can guide targeted intervention selection for perinatal women.

Trauma can cause dysfunctional fear regulation leading some people to develop disorders, such as post-traumatic stress disorder (PTSD). The amygdala regulates fear, whereas PACAP (pituitary adenylate activating peptide) and PAC1 receptors are linked to PTSD symptom severity at genetic/epigenetic levels, with a strong link in females with PTSD. We discovered a PACAPergic projection from the basomedial amygdala (BMA) to the medial intercalated cells (mICCs) in adult mice. In vivo optogenetic stimulation of this pathway increased CFOS expression in mICCs, decreased fear recall, and increased fear extinction. Selective deletion of PAC1 receptors from the mICCs in females reduced fear acquisition, but enhanced fear generalization and reduced fear extinction in males. Optogenetic stimulation of the BMA-mICC PACAPergic pathway produced EPSCs in mICC neurons, which were enhanced by the PAC1 receptor antagonist, PACAP 6-38. Our findings show that mICCs modulate contextual fear in a dynamic and sex-dependent manner via a microcircuit containing the BMA and mICCs, and in a manner that was dependent on behavioral state.SIGNIFICANCE STATEMENT Traumatic stress can affect different aspects of fear behaviors, including fear learning, generalization of learned fear to novel contexts, how the fear of the original context is recalled, and how fear is reduced over time. While the amygdala has been studied for its role in regulation of different aspects of fear, the molecular circuitry of this structure is quite complex. In addition, aspects of fear can be modulated differently in males and females. Our findings show that a specific circuitry containing the neuropeptide PACAP and its receptor, PAC1, regulates various aspects of fear, including acquisition, generalization, recall, and extinction in a sexually dimorphic manner, characterizing a novel pathway that modulates traumatic fear.

The understanding and treatment of psychiatric disorders, which are known to be neurobiologically and clinically heterogeneous, could benefit from the data-driven identification of disease subtypes. Here, we report the identification of two clinically relevant subtypes of post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) on the basis of robust and distinct functional connectivity patterns, prominently within the frontoparietal control network and the default mode network. We identified the disease subtypes by analysing, via unsupervised and supervised machine learning, the power-envelope-based connectivity of signals reconstructed from high-density resting-state electroencephalography in four datasets of patients with PTSD and MDD, and show that the subtypes are transferable across independent datasets recorded under different conditions. The subtype whose functional connectivity differed most from those of healthy controls was less responsive to psychotherapy treatment for PTSD and failed to respond to an antidepressant medication for MDD. By contrast, both subtypes responded equally well to two different forms of repetitive transcranial magnetic stimulation therapy for MDD. Our data-driven approach may constitute a generalizable solution for connectome-based diagnosis.

ObjectiveWe examined whether intraindividual variability (IIV) across tests of executive functions (EF-IIV) is elevated in Veterans with a history of mild traumatic brain injury (mTBI) relative to military controls (MCs) without a history of mTBI. We also explored relationships among EF-IIV, white matter microstructure, and posttraumatic stress disorder (PTSD) symptoms.MethodA total of 77 Veterans (mTBI = 43, MCs = 34) completed neuropsychological testing, diffusion tensor imaging (DTI), and PTSD symptom ratings. EF-IIV was calculated as the standard deviation across six tests of EF, along with an EF-Mean composite. DSI Studio connectometry analysis identified white matter tracts significantly associated with EF-IIV according to generalized fractional anisotropy (GFA).ResultsAfter adjusting for EF-Mean and PTSD symptoms, the mTBI group showed significantly higher EF-IIV than MCs. Groups did not differ on EF-Mean after adjusting for PTSD symptoms. Across groups, PTSD symptoms significantly negatively correlated with EF-Mean, but not with EF-IIV. EF-IIV significantly negatively correlated with GFA in multiple white matter pathways connecting frontal and more posterior regions.ConclusionsVeterans with mTBI demonstrated significantly greater IIV across EF tests compared to MCs, even after adjusting for mean group differences on those measures as well as PTSD severity. Findings suggest that, in contrast to analyses that explore effects of mean performance across tests, discrepancy analyses may capture unique variance in neuropsychological performance and more sensitively capture cognitive disruption in Veterans with mTBI histories. Importantly, findings show that EF-IIV is negatively associated with the microstructure of white matter pathways interconnecting cortical regions that mediate executive function and attentional processes.

Traumatic brain injury (TBI) is common among military personnel and the civilian population and is often followed by a heterogeneous array of clinical, cognitive, behavioral, mood, and neuroimaging changes. Unlike many neurological disorders that have a characteristic abnormal central neurologic area(s) of abnormality pathognomonic to the disorder, a sufficient head impact may cause focal, multifocal, diffuse or combination of injury to the brain. This inconsistent presentation makes it difficult to establish or validate biological and imaging markers that could help improve diagnostic and prognostic accuracy in this patient population. The purpose of this manuscript is to describe both the challenges and opportunities when conducting military-relevant TBI research and introduce the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Military Brain Injury working group. ENIGMA is a worldwide consortium focused on improving replicability and analytical power through data sharing and collaboration. In this paper, we discuss challenges affecting efforts to aggregate data in this patient group. In addition, we highlight how "big data" approaches might be used to understand better the role that each of these variables might play in the imaging and functional phenotypes of TBI in Service member and Veteran populations, and how data may be used to examine important military specific issues such as return to duty, the late effects of combat-related injury, and alteration of the natural aging processes.

ObjectivePost-traumatic stress disorder (PTSD) is common in Veterans. Symptoms can perpetuate into late life, negatively impacting physical and mental health. Exercise and social support are beneficial in treating anxiety disorders such as PTSD in the general population, although less is known about the impact on Veterans who have lived with PTSD for decades. This study assessed associations between social connectedness, physical function and self-reported change in PTSD symptoms among older Veterans specifically participating in Gerofit.DesignProspective clinical intervention.SettingTwelve sites of Veterans Affairs (VA) Gerofit exercise program across the United States.ParticipantsThree hundred and twenty one older Veteran Gerofit participants (mean age = 74) completed physical assessments and questionnaires regarding physical and emotional symptoms and their experience.MeasurementsMeasures of physical function, including 30-second chair stands, 10-m and 6-min walk were assessed at baseline and 3 months; change in PTSD symptoms based on the Diagnostic Statistical Manual-5 (DSM-5) assessed by a self-report questionnaire; and social connection measured by the Relatedness Subscale of the Psychological Need Satisfaction in Exercise scale (PNSE) were evaluated after 3 months of participation in Gerofit.ResultsNinety five (29.6%) Veterans reported PTSD. Significant improvement was noted in self-rated PTSD symptoms at 3 months (P

BackgroundResearch suggests four modal trajectories of psychological symptoms after traumatic injury: Resilient, Chronic, Delayed Onset, Recovery. However, most studies focus on symptoms of psychiatric disorders (e.g., posttraumatic stress disorder, depression), which are limited by heterogeneity and symptom overlap. We examined trajectories of cross-cutting posttraumatic symptom dimensions following traumatic injury and predictors of trajectory membership.MethodsIn this longitudinal study of 427 predominantly Hispanic/Latino traumatic injury survivors, posttraumatic psychopathology symptoms were assessed during hospitalization and approximately one and five months post-trauma. Using latent class growth analysis, we estimated trajectories of several posttraumatic symptom dimensions: re-experiencing, avoidance, anxious arousal, numbing, dysphoric arousal, loss, and threat. We then examined sociodemographic and trauma-related characteristics (measured during hospitalization) as predictors of trajectory membership for each dimension.ResultsFour trajectories (Resilient, Chronic, Delayed Onset, Recovery) emerged for all dimensions except loss and threat, which manifested three trajectories (Resilient, Chronic, Delayed Onset). Across dimensions, membership in the Chronic (vs. Resilient) trajectory was consistently predicted by unemployment (7 of 7 dimensions), followed by older age (3/7), female sex (3/7), and assaultive trauma (2/7). For several dimensions, unemployment also distinguished between participants who presented with similar symptom levels days after trauma, but then diverged over time.LimitationsMeasures of posttraumatic symptom dimension constructs differed across assessments.ConclusionsThis study provides evidence of distinct trajectories across transdiagnostic symptom dimensions after traumatic injury. Employment status emerged as the most important predictor of trajectory membership. Research is needed to better understand the etiologies and consequences of these posttraumatic symptom dimension trajectories.

BackgroundThere is a paucity of long-term prospective disaster studies of the psychological sequelae among survivors.MethodsAt 1½ and 25 years after the Spitak earthquake, 142 early adolescents from two cities were assessed: Gumri (moderate-severe exposure) and Spitak (very severe exposure). The Gumri group included treated and not-treated subjects, while the Spitak group included not-treated subjects. Instruments included: DSM-III-R PTSD-Reaction Index (PTSD-RI); DSM-5 PTSD-Checklist (PCL); Depression Self-Rating Scale (DSRS); and Center for Epidemiological Studies-Depression Scale (CES-D).Results(1) Between 1½ and 25 years, PTSD rates and mean scores decreased significantly in the three groups (over 50%). However, at 25 years 9.1-22.4% met DSM-5 PTSD criteria. (2) At 1½ years, the Spitak group had higher PTSD-RI (p < 0.001) and DSRS scores (p < 0.001) compared to the Gumri-not-treated group. At 25 years, the Spitak group that had experienced fewer post-earthquake adversities (p < 0.03), had a greater decrease in PTSD-RI scores (p < 0.02), and lower CES-D scores (p < 0.01). (3) Before treatment, PTSD-RI and DSRS scores did not differ between the Gumri-treated and not-treated groups. At 25-years, the Gumri-treated group showed a greater decrease in PTSD-RI scores (p < 0.03), and lower mean PTSD-RI (p < 0.02), PCL (p < 0.02), and CES-D (p < 0.01) scores. (4) Predictors of PTSD symptom severity at 25-years included: home destruction, treatment, social support, post-earthquake adversities, and chronic medical illnesses.ConclusionPost-disaster PTSD and depressive symptoms can persist for decades. Trauma-focused treatment, alleviation of post-disaster adversities, improving the social ecology, and monitoring for chronic medical illnesses are essential components of recovery programs.

ObjectiveThe purpose of the current study was to examine the prevalence and trajectory of posttraumatic stress disorder (PTSD) symptoms among patients with eating disorders (EDs) in higher level of ED care with trauma-informed components, but without a formal evidence-based trauma intervention.MethodParticipants were 613 adults diagnosed with EDs receiving treatment at inpatient, residential, or partial hospitalization levels of care. Participants completed the PTSD Checklist-5 (PCL-5) at admission and discharge.ResultsOver half of patients scored above the cutoff of 33 on the PCL-5 at admission, suggestive of PTSD symptoms characteristic of a formal PTSD diagnosis. The average PCL-5 score significantly decreased for every ED diagnostic category, and there was a significant reduction in the proportion of patients above the PCL-5 cutoff score at discharge. PCL-5 subscales measuring PTSD criteria B (intrusions) and C (avoidance) improved with modest effect sizes, whereas PCL-5 subscales D (negative alterations in cognitions and mood) and E (alterations in arousal and reactivity) improved with larger effect sizes.DiscussionPTSD symptoms are prevalent among patients with EDs seeking higher levels of care. Despite not offering evidence-based trauma-specific interventions, PTSD symptoms decreased over the course of treatment. However, improvements cannot definitely be attributed to trauma-informed care.