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Background Physical activity is increasingly recognized as an important modifiable factor for depression. However, the extent to which individuals with stable risk factors for depression, such as high genetic vulnerability, can benefit from the protective effects of physical activity, remains unknown. Using a longitudinal biobank cohort integrating genomic data from 7,968 individuals of European ancestry with high-dimensional electronic health records and lifestyle survey responses, we examined whether physical activity was prospectively associated with reduced risk for incident depression in the context of genetic vulnerability. Methods We identified individuals with incident episodes of depression, based on two or more diagnostic billing codes for a depressive disorder within 2 years following their lifestyle survey, and no such codes in the year prior. Polygenic risk scores were derived based on large-scale genome-wide association results for major depression. We tested main effects of physical activity and polygenic risk scores on incident depression, and effects of physical activity within stratified groups of polygenic risk. Results Polygenic risk was associated with increased odds of incident depression, and physical activity showed a protective effect of similar but opposite magnitude, even after adjusting for BMI, employment status, educational attainment, and prior depression. Higher levels of physical activity were associated with reduced odds of incident depression across all levels of genetic vulnerability, even among individuals at highest polygenic risk. Conclusions Real-world data from a large healthcare system suggest that individuals with high genetic vulnerability are more likely to avoid incident episodes of depression if they are physically active.

Most studies investigating the effect of childhood trauma on the brain are retrospective and mainly focus on maltreatment, whereas different types of trauma exposure such as growing up in a violent neighborhood, as well as developmental stage, could have differential effects on brain structure and function. The current magnetic resonance imaging study assessed the effect of trauma exposure broadly and violence exposure more specifically, as well as developmental stage on the fear neurocircuitry in 8- to 14-year-old children and adolescents (N = 69). We observed reduced hippocampal and increased amygdala volume with increasing levels of trauma exposure. Second, higher levels of violence exposure were associated with increased activation in the amygdala, hippocampus, and ventromedial prefrontal cortex during emotional response inhibition. This association was specifically observed in children younger than 10 years. Finally, increased functional connectivity between the amygdala and brainstem was associated with higher levels of violence exposure. Based on the current findings, it could be hypothesized that trauma exposure during childhood results in structural changes that are associated with later risk for psychiatric disorders. At the same time, it could be postulated that growing up in an unsafe environment leads the brain to functionally adapt to this situation in a way that promotes survival, where the long-term costs or consequences of these adaptations are largely unknown and an area for future investigations.

Background Self-assessment of resilience could prove valuable to military and other organizations whose personnel confront foreseen stressors. We evaluated the validity of self-assessed resilience among U.S. Army soldiers, including whether predeployment perceived resilience predicted postdeployment emotional disorder. Methods Resilience was assessed via self-administered questionnaire among new soldiers reporting for basic training (N = 35,807) and experienced soldiers preparing to deploy to Afghanistan (N = 8,558). Concurrent validity of self-assessed resilience was evaluated among recruits by estimating its association with past-month emotional disorder. Predictive validity was examined among 3,526 experienced soldiers with no lifetime emotional disorder predeployment. Predictive models estimated associations of predeployment resilience with incidence of emotional disorder through 9 months postdeployment and with marked improvement in coping at 3 months postdeployment. Weights-adjusted regression models incorporated stringent controls for risk factors. Results Soldiers characterized themselves as very resilient on average [M = 14.34, SD = 4.20 (recruits); M = 14.75, SD = 4.31 (experienced soldiers); theoretical range = 0–20]. Demographic characteristics exhibited only modest associations with resilience, while severity of childhood maltreatment was negatively associated with resilience in both samples. Among recruits, resilience was inversely associated with past-month emotional disorder [adjusted odds ratio (AOR) = 0.65, 95% CI = 0.62–0.68, P < .0005 (per standard score increase)]. Among deployed soldiers, greater predeployment resilience was associated with decreased incidence of emotional disorder (AOR = 0.91; 95% CI = 0.84–0.98; P = .016) and increased odds of improved coping (AOR = 1.36; 95% CI = 1.24–1.49; P < .0005) postdeployment. Conclusions Findings supported validity of self-assessed resilience among soldiers, although its predictive effect on incidence of emotional disorder was modest. In conjunction with assessment of known risk factors, measurement of resilience could help predict adaptation to foreseen stressors like deployment.

Background Although several short-forms of the posttraumatic stress disorder (PTSD) Checklist (PCL) exist, all were developed using heuristic methods. This report presents the results of analyses designed to create an optimal short-form PCL for DSM-5 (PCL-5) using both machine learning and conventional scale development methods. Methods The short-form scales were developed using independent datasets collected by the Army Study to Assess Risk and Resilience among Service members. We began by using a training dataset (n = 8,917) to fit short-form scales with between 1 and 8 items using different statistical methods (exploratory factor analysis, stepwise logistic regression, and a new machine learning method to find an optimal integer-scored short-form scale) to predict dichotomous PTSD diagnoses determined using the full PCL-5. A smaller subset of best short-form scales was then evaluated in an independent validation sample (n = 11,728) to select one optimal short-form scale based on multiple operating characteristics (area under curve [AUC], calibration, sensitivity, specificity, net benefit). Results Inspection of AUCs in the training sample and replication in the validation sample led to a focus on 4-item integer-scored short-form scales selected with stepwise regression. Brier scores in the validation sample showed that a number of these scales had comparable calibration (0.015-0.032) and AUC (0.984-0.994), but that one had consistently highest net benefit across a plausible range of decision thresholds. Conclusions The recommended 4-item integer-scored short-form PCL-5 generates diagnoses that closely parallel those of the full PCL-5, making it well-suited for screening.

Background Exposure therapy, a gold-standard treatment for anxiety disorders, is assumed to work via extinction learning, but this has never been tested. Anxious individuals demonstrate extinction learning deficits, likely related to less ventromedial prefrontal cortex (vmPFC) and more amygdala activation, but the relationship between these deficits and exposure outcome is unknown. We tested whether anxious individuals who demonstrate better extinction learning report greater anxiety reduction following brief exposure. Methods Twenty-four adults with public speaking anxiety completed (1) functional magnetic resonance imaging during a conditioning paradigm, (2) a speech exposure session, and (3) anxiety questionnaires before and two weeks postexposure. Extinction learning was assessed by comparing ratings to a conditioned stimulus (neutral image) that was previously paired with an aversive noise against a stimulus that had never been paired. Robust regression analyses examined whether brain activation during extinction learning predicted anxiety reduction two weeks postexposure. Results On average, the conditioning paradigm resulted in acquisition and extinction effects on stimulus ratings, and the exposure session resulted in reduced anxiety two weeks post-exposure. Consistent with our hypothesis, individuals with better extinction learning (less negative stimulus ratings), greater activation in vmPFC, and less activation in amygdala, insula, and periaqueductal gray reported greater anxiety reduction two weeks postexposure. Conclusion To our knowledge, this is the first time that the theoretical link between extinction learning and exposure outcome has been demonstrated. Future work should examine whether extinction learning can be used as a prognostic test to determine who is most likely to benefit from exposure therapy.

Background Many patients with anxiety disorders remain symptomatic after receiving evidence-based treatment, yet research on treatment-resistant anxiety is limited. We evaluated effects of cognitive behavioral therapy (CBT) on outcomes of patients with medication-resistant anxiety disorders using data from the Coordinated Anxiety Learning and Management (CALM) trial. Methods Primary care patients who met study entry criteria (including DSM-IV diagnosis of generalized anxiety disorder, panic disorder, posttraumatic stress disorder, or social anxiety disorder) despite ongoing pharmacotherapy of appropriate type, dose, and duration were classified as medication resistant (n = 227). Logistic regression was used to estimate effects of CALM's CBT program (CALM-CBT; chosen by 104 of 117 medication-resistant patients randomized to CALM) versus usual care (UC; n = 110) on response [≥ 50% reduction of 12-item Brief Symptom Inventory (BSI-12) anxiety and somatic symptom score] and remission (BSI-12 < 6) at 6, 12, and 18 months. Within-group analyses examined outcomes by treatment choice (CBT vs. CBT plus medication management) and CBT dose. Results Approximately 58% of medication-resistant CALM-CBT patients responded and 46% remitted during the study. Relative to UC, CALM-CBT was associated with greater response at 6 months (AOR = 3.78, 95% CI 2.02-7.07) and 12 months (AOR = 2.49, 95% CI 1.36-4.58) and remission at 6, 12, and 18 months (AORs = 2.44 to 3.18). Patients in CBT plus medication management fared no better than those in CBT only. Some evidence suggested higher CBT dose produced better outcomes. Conclusions CBT can improve outcomes for patients whose anxiety symptoms are resistant to standard pharmacotherapy.

OBJECTIVE: This study examined cross-sectional and longitudinal relationships between educational attainment and psychiatric disorders (i.e., mood, anxiety, substance use, and personality disorders) using a nationally representative survey of US adults. METHOD: We used data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (N = 34,653). Bivariate and multiple logistic regressions examined cross-sectional and longitudinal associations between educational attainment and a variety of past-year and incident anxiety, mood, and substance use disorders, controlling for sociodemographics and psychiatric disorder comorbidity. RESULTS: Adjusted cross-sectional data indicated that educational attainment below a graduate or professional degree at Wave 2 was associated with significantly higher odds of substance use and/or dependence disorders (adjusted odds ratio range (AORR = 1.55-2.55, P CONCLUSION: Findings lend support to other published research demonstrating that educational attainment is protective against developing a spectrum of psychiatric disorders. Mechanisms underlying this relationship are speculative and in need of additional research.© 2016 Wiley Periodicals, Inc. Language: en

BACKGROUND: Prior investigations have found negative associations between military unit cohesion and posttraumatic stress disorder (PTSD); however, most relied on cross-sectional data and few examined relationships of unit cohesion to other mental disorders. This study evaluates prospective associations of perceived unit cohesion with a range of mental health outcomes following combat deployment. METHODS: US Army soldiers were surveyed approximately 1–2 months before deployment to Afghanistan (T0); and 1 month (T1), 3 months (T2), and 9 months (T3) after return from deployment. Logistic regression was performed to estimate associations of perceived unit cohesion at T0 with risk of PTSD, major depressive episode (MDE), generalized anxiety disorder (GAD), alcohol or substance use disorder (AUD/SUD), and suicidal ideation at T2 or T3 among soldiers who completed all study assessments (N=4,645). Models adjusted for socio-demographic and Army service characteristics, pre-deployment history of the index outcome, and deployment stress exposure. RESULTS: Higher perceived unit cohesion at T0 was associated with lower risk of PTSD, MDE, GAD, AUD/SUD, and suicidal ideation at T2 or T3 (AORs=0.72 to 0.85 per standard score increase in unit cohesion; ps

Background Most people with suicide ideation (SI) do not attempt suicide (SA). Understanding the transition from current/recent SI to SA is important for mental health care. Our objective was to identify characteristics that differentiate SA from 30-day SI among representative U.S. Army soldiers. Methods Using a unique case-control design, soldiers recently hospitalized for SA (n = 132) and representative soldiers from the same four communities (n = 10,193) were administered the same questionnaire. We systematically identified variables that differentiated suicide attempters from the total population, then examined whether those same variables differentiated all 30-day ideators (n = 257) from the total population and attempters from nonattempting 30-day ideators. Results In univariable analyses, 20 of 23 predictors were associated with SA in the total population (0.05 level). The best multivariable model included eight significant predictors: interpersonal violence, relationship problems, major depressive disorder, posttraumatic stress disorder (PTSD), and substance use disorder (all having positive associations), as well as past 12-month combat trauma, intermittent explosive disorder (IED), and any college education (all having negative associations). Six of these differentiated 30-day ideators from the population. Three differentiated attempters from ideators: past 30-day PTSD (OR = 6.7 [95% CI = 1.1-39.4]), past 30-day IED (OR = 0.2 [95% CI = 0.1-0.5]), and any college education (OR = 0.1 [95% CI = 0.0-0.6]). The 5% of ideators with highest predicted risk in this final model included 20.9% of attempters, a four-fold concentration of risk. Conclusions Prospective army research examining transition from SI to SA should consider PTSD, IED, and education. Combat exposure did not differentiate attempters from ideators. Many SA risk factors in the Army population are actually risk factors for SI.