Social network size and personality traits independently and prospectively predict distress disorders and suicidal behavior in U.S. Army soldiers.

BACKGROUND: Personality traits (e.g. neuroticism) and the social environment predict risk for internalizing disorders and suicidal behavior. Studying these characteristics together and prospectively within a population confronted with high stressor exposure (e.g. U.S. Army soldiers) has not been done, yet could uncover unique and interactive predictive effects that may inform prevention and early intervention efforts. METHODS: Five broad personality traits and social network size were assessed via self-administered questionnaires among experienced soldiers preparing for deployment (N = 4645) and new soldiers reporting for basic training (N = 6216). Predictive models examined associations of baseline personality and social network variables with recent distress disorders or suicidal behaviors assessed 3- and 9-months post-deployment and approximately 5 years following enlistment. RESULTS: Among the personality traits, elevated neuroticism was consistently associated with increased mental health risk following deployment. Small social networks were also associated with increased mental health risk following deployment, beyond the variance accounted for by personality. Limited support was found for social network size moderating the association between personality and mental health outcomes. Small social networks also predicted distress disorders and suicidal behavior 5 years following enlistment, whereas unique effects of personality traits on these more distal outcomes were rare. CONCLUSIONS: Heightened neuroticism and small social networks predict a greater risk for negative mental health sequelae, especially following deployment. Social ties may mitigate adverse impacts of personality traits on psychopathology in some contexts. Early identification and targeted intervention for these distinct, modifiable factors may decrease the risk of distress disorders and suicidal behavior.

Effects of prior deployments and perceived resilience on anger trajectories of combat-deployed soldiers.

BACKGROUND: Problematic anger is frequently reported by soldiers who have deployed to combat zones. However, evidence is lacking with respect to how anger changes over a deployment cycle, and which factors prospectively influence change in anger among combat-deployed soldiers. METHODS: Reports of problematic anger were obtained from 7298 US Army soldiers who deployed to Afghanistan in 2012. A series of mixed-effects growth models estimated linear trajectories of anger over a period of 1-2 months before deployment to 9 months post-deployment, and evaluated the effects of pre-deployment factors (prior deployments and perceived resilience) on average levels and growth of problematic anger. RESULTS: A model with random intercepts and slopes provided the best fit, indicating heterogeneity in soldiers' levels and trajectories of anger. First-time deployers reported the lowest anger overall, but the most growth in anger over time. Soldiers with multiple prior deployments displayed the highest anger overall, which remained relatively stable over time. Higher pre-deployment resilience was associated with lower reports of anger, but its protective effect diminished over time. First- and second-time deployers reporting low resilience displayed different anger trajectories (stable v. decreasing, respectively). CONCLUSIONS: Change in anger from pre- to post-deployment varies based on pre-deployment factors. The observed differences in anger trajectories suggest that efforts to detect and reduce problematic anger should be tailored for first-time v. repeat deployers. Ongoing screening is needed even for soldiers reporting high resilience before deployment, as the protective effect of pre-deployment resilience on anger erodes over time.

Associations of polygenic risk scores with posttraumatic stress symptom trajectories following combat deployment.

BACKGROUND: Identification of genetic risk factors may inform the prevention and treatment of posttraumatic stress disorder (PTSD). This study evaluates the associations of polygenic risk scores (PRS) with patterns of posttraumatic stress symptoms following combat deployment. METHOD: US Army soldiers of European ancestry (n = 4900) provided genomic data and ratings of posttraumatic stress symptoms before and after deployment to Afghanistan in 2012. Latent growth mixture modeling was used to model posttraumatic stress symptom trajectories among participants who provided post-deployment data (n = 4353). Multinomial logistic regression models tested independent associations between trajectory membership and PRS for PTSD, major depressive disorder (MDD), schizophrenia, neuroticism, alcohol use disorder, and suicide attempt, controlling for age, sex, ancestry, and exposure to potentially traumatic events, and weighted to account for uncertainty in trajectory classification and missing data. RESULTS: Participants were classified into low-severity (77.2%), increasing-severity (10.5%), decreasing-severity (8.0%), and high-severity (4.3%) posttraumatic stress symptom trajectories. Standardized PTSD-PRS and MDD-PRS were associated with greater odds of membership in the high-severity v. low-severity trajectory [adjusted odds ratios and 95% confidence intervals, 1.23 (1.06-1.43) and 1.18 (1.02-1.37), respectively] and the increasing-severity v. low-severity trajectory [1.12 (1.01-1.25) and 1.16 (1.04-1.28), respectively]. Additionally, MDD-PRS was associated with greater odds of membership in the decreasing-severity v. low-severity trajectory [1.16 (1.03-1.31)]. No other associations were statistically significant. CONCLUSIONS: Higher polygenic risk for PTSD or MDD is associated with more severe posttraumatic stress symptom trajectories following combat deployment. PRS may help stratify at-risk individuals, enabling more precise targeting of treatment and prevention programs.

Unit cohesion during deployment and post-deployment mental health: is cohesion an individual- or unit-level buffer for combat-exposed soldiers?

BACKGROUND: Unit cohesion may protect service member mental health by mitigating effects of combat exposure; however, questions remain about the origins of potential stress-buffering effects. We examined buffering effects associated with two forms of unit cohesion (peer-oriented horizontal cohesion and subordinate-leader vertical cohesion) defined as either individual-level or aggregated unit-level variables. METHODS: Longitudinal survey data from US Army soldiers who deployed to Afghanistan in 2012 were analyzed using mixed-effects regression. Models evaluated individual- and unit-level interaction effects of combat exposure and cohesion during deployment on symptoms of post-traumatic stress disorder (PTSD), depression, and suicidal ideation reported at 3 months post-deployment (model n's = 6684 to 6826). Given the small effective sample size (k = 89), the significance of unit-level interactions was evaluated at a 90% confidence level. RESULTS: At the individual-level, buffering effects of horizontal cohesion were found for PTSD symptoms [B = -0.11, 95% CI (-0.18 to -0.04), p < 0.01] and depressive symptoms [B = -0.06, 95% CI (-0.10 to -0.01), p < 0.05]; while a buffering effect of vertical cohesion was observed for PTSD symptoms only [B = -0.03, 95% CI (-0.06 to -0.0001), p < 0.05]. At the unit-level, buffering effects of horizontal (but not vertical) cohesion were observed for PTSD symptoms [B = -0.91, 90% CI (-1.70 to -0.11), p = 0.06], depressive symptoms [B = -0.83, 90% CI (-1.24 to -0.41), p < 0.01], and suicidal ideation [B = -0.32, 90% CI (-0.62 to -0.01), p = 0.08]. CONCLUSIONS: Policies and interventions that enhance horizontal cohesion may protect combat-exposed units against post-deployment mental health problems. Efforts to support individual soldiers who report low levels of horizontal or vertical cohesion may also yield mental health benefits.

Dissecting the heterogeneity of posttraumatic stress disorder: differences in polygenic risk, stress exposures, and course of PTSD subtypes.

BACKGROUND: Definition of disorder subtypes may facilitate precision treatment for posttraumatic stress disorder (PTSD). We aimed to identify PTSD subtypes and evaluate their associations with genetic risk factors, types of stress exposures, comorbidity, and course of PTSD. METHODS: Data came from a prospective study of three U.S. Army Brigade Combat Teams that deployed to Afghanistan in 2012. Soldiers with probable PTSD (PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition ≥31) at three months postdeployment comprised the sample (N = 423) for latent profile analysis using Gaussian mixture modeling and PTSD symptom ratings as indicators. PTSD profiles were compared on polygenic risk scores (derived from external genomewide association study summary statistics), experiences during deployment, comorbidity at three months postdeployment, and persistence of PTSD at nine months postdeployment. RESULTS: Latent profile analysis revealed profiles characterized by prominent intrusions, avoidance, and hyperarousal (threat-reactivity profile; n = 129), anhedonia and negative affect (dysphoric profile; n = 195), and high levels of all PTSD symptoms (high-symptom profile; n = 99). The threat-reactivity profile had the most combat exposure and the least comorbidity. The dysphoric profile had the highest polygenic risk for major depression, and more personal life stress and co-occurring major depression than the threat-reactivity profile. The high-symptom profile had the highest rates of concurrent mental disorders and persistence of PTSD. CONCLUSIONS: Genetic and trauma-related factors likely contribute to PTSD heterogeneity, which can be parsed into subtypes that differ in symptom expression, comorbidity, and course. Future studies should evaluate whether PTSD typology modifies treatment response and should clarify distinctions between the dysphoric profile and depressive disorders.

Risk Factors for Suicidal Ideation Following Mild Traumatic Brain Injury: A TRACK-TBI Study.

OBJECTIVE: To identify risk factors for suicidal ideation (SI) following mild traumatic brain injury (mTBI). SETTING: Eleven US level 1 trauma centers. PARTICIPANTS: A total of 1158 emergency department patients with mTBI (Glasgow Coma Scale score = 13-15) enrolled in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study. DESIGN: Prospective observational study; weights-adjusted multivariable logistic regression models (n's = 727-883) estimated associations of baseline factors and post-TBI symptoms with SI at 2 weeks and 3, 6, and 12 months postinjury. MAIN MEASURES: Patient Health Questionnaire, Rivermead Post-Concussion Symptoms Questionnaire. RESULTS: Preinjury psychiatric history predicted SI at all follow-ups (adjusted odds ratios [AORs] = 2.26-6.33, P values <.05) and history of prior TBI predicted SI at 2 weeks (AOR = 2.36, 95% confidence interval [CI] = 1.16-4.81, P = .018), 3 months (AOR = 2.62, 95% CI = 1.33-5.16, P = .005), and 6 months postinjury (AOR = 2.54, 95% CI = 1.19-5.42, P = .016). Adjusting for these baseline factors, post-TBI symptoms were strongly associated with SI at concurrent (AORs = 1.91-2.88 per standard deviation unit increase in Rivermead Post-Concussion Symptoms Questionnaire score; P values <.0005) and subsequent follow-up visits (AORs = 1.68-2.53; P values <.005). Most of the associations between post-TBI symptoms and SI were statistically explained by co-occurring depression. CONCLUSION: Screening for psychiatric and prior TBI history may help identify patients at risk for SI following mTBI. Awareness of the strong associations of post-TBI symptoms with SI may facilitate interventions to prevent suicide-related outcomes in patients with mTBI.

Polygenic risk for major depression is associated with lifetime suicide attempt in US soldiers independent of personal and parental history of major depression.

Suicide is a major public health problem. The contribution of common genetic variants for major depressive disorder (MDD) independent of personal and parental history of MDD has not been established. Polygenic risk score (using PRS-CS) for MDD was calculated for US Army soldiers of European ancestry. Associations between polygenic risk for MDD and lifetime suicide attempt (SA) were tested in models that also included parental or personal history of MDD. Models were adjusted for age, sex, tranche (where applicable), and 10 principal components reflecting ancestry. In the first cohort, 417 (6.3%) of 6,573 soldiers reported a lifetime history of SA. In a multivariable model that included personal [OR = 3.83, 95% CI:3.09-4.75] and parental history of MDD [OR = 1.43, 95% CI:1.13-1.82 for one parent and OR = 1.64, 95% CI:1.20-2.26 for both parents), MDD PRS was significantly associated with SA (OR = 1.22 [95% CI:1.10-1.36]). In the second cohort, 204 (4.2%) of 4,900 soldiers reported a lifetime history of SA. In a multivariable model that included personal [OR = 3.82, 95% CI:2.77-5.26] and parental history of MDD [OR = 1.42, 95% CI:0.996-2.03 for one parent and OR = 2.21, 95% CI:1.33-3.69 for both parents) MDD PRS continued to be associated (at p = .0601) with SA (OR = 1.15 [95% CI:0.994-1.33]). A soldier's PRS for MDD conveys information about likelihood of a lifetime SA beyond that conveyed by two predictors readily obtainable by interview: personal or parental history of MDD. Results remain to be extended to prospective prediction of incident SA. These findings portend a role for PRS in risk stratification for suicide attempts.

Prospective study of polygenic risk, protective factors, and incident depression following combat deployment in US Army soldiers.

BACKGROUND: Whereas genetic susceptibility increases the risk for major depressive disorder (MDD), non-genetic protective factors may mitigate this risk. In a large-scale prospective study of US Army soldiers, we examined whether trait resilience and/or unit cohesion could protect against the onset of MDD following combat deployment, even in soldiers at high polygenic risk. METHODS: Data were analyzed from 3079 soldiers of European ancestry assessed before and after their deployment to Afghanistan. Incident MDD was defined as no MDD episode at pre-deployment, followed by a MDD episode following deployment. Polygenic risk scores were constructed from a large-scale genome-wide association study of major depression. We first examined the main effects of the MDD PRS and each protective factor on incident MDD. We then tested the effects of each protective factor on incident MDD across strata of polygenic risk. RESULTS: Polygenic risk showed a dose-response relationship to depression, such that soldiers at high polygenic risk had greatest odds for incident MDD. Both unit cohesion and trait resilience were prospectively associated with reduced risk for incident MDD. Notably, the protective effect of unit cohesion persisted even in soldiers at highest polygenic risk. CONCLUSIONS: Polygenic risk was associated with new-onset MDD in deployed soldiers. However, unit cohesion - an index of perceived support and morale - was protective against incident MDD even among those at highest genetic risk, and may represent a potent target for promoting resilience in vulnerable soldiers. Findings illustrate the value of combining genomic and environmental data in a prospective design to identify robust protective factors for mental health.

The Association of Lifetime and Deployment-Acquired Traumatic Brain Injury With Postdeployment Binge and Heavy Drinking.

OBJECTIVE: To investigate associations of lifetime traumatic brain injury (LT-TBI) prior to an index deployment, and/or deployment-acquired TBI (DA-TBI), with postdeployment binge and heavy drinking. SETTING: Soldiers from 3 Brigade Combat Teams deployed to Afghanistan in 2012. PARTICIPANTS: A total of 4645 soldiers who participated in the Army STARRS Pre/Post Deployment Study and completed 4 assessments: T0 (1-2 months predeployment), T1 (upon return to United States), T2 (3 months postdeployment), and T3 (9 months postdeployment). DESIGN: Prospective, longitudinal study controlling for baseline binge drinking. MAIN MEASURES: Self-reported past month binge drinking (5+ alcoholic beverages on the same day) and past month heavy drinking (binge drinking at least weekly) at T2 and T3. RESULTS: In total, 34.3% screened positive for LT-TBI, and 19.2% screened positive for DA-TBI. At T2 only, LT-TBI, but not DA-TBI, was associated with increased odds of binge drinking (adjusted odds ratio [AOR] = 1.39, 95% confidence interval [CI]: 1.20-1.60, P < .001) and heavy drinking (AOR = 1.28, 95% CI: 1.09-1.49, P = .007). Among the subgroup with LT-TBI, also having DA-TBI was associated with increased risk of heavy drinking at T3 (AOR = 1.42, 95% CI: 1.03-1.95, P = .047). CONCLUSION: Routine screening for LT-TBI may help target efforts to prevent alcohol misuse among military members.

Associations of Lifetime Traumatic Brain Injury Characteristics With Prospective Suicide Attempt Among Deployed US Army Soldiers.

OBJECTIVE: To estimate associations of lifetime traumatic brain injury (TBI) characteristics with prospective suicide attempt among US Army soldiers. METHOD: The Army STARRS (Study to Assess Risk and Resilience in Servicemembers) Pre/Post Deployment Study surveyed 3 Brigade Combat Teams that were deployed to Afghanistan in 2012. Lifetime TBI and past-month postconcussive/post-TBI symptoms were evaluated at predeployment baseline. Recency and number of TBIs were quantified, and TBI severity was classified on the basis of reports of alteration/loss of consciousness and memory lapse. Suicide attempt data came from administrative records and surveys administered after return from deployment. Logistic regression models estimated associations of TBI characteristics with prospective suicide attempt among baseline respondents who were deployed (n = 7677), adjusting for other risk factors including lifetime mental disorder. RESULTS: One hundred three soldiers made a suicide attempt over a median follow-up period of 30 months (weighted prevalence = 1.31% [0.14%]). In the final model estimating joint associations of TBI severity/recency and past-month postconcussive/post-TBI symptoms, only postconcussive/post-TBI symptoms were associated with a higher risk of suicide attempt (per standard score increase: AOR [adjusted odds ratio] = 1.31; 95% CI, 1.05-1.63; P = .012). CONCLUSIONS: Among the lifetime TBI characteristics evaluated at predeployment baseline, only past-month postconcussive/post-TBI symptoms were prospectively associated with an increased risk of suicide attempt following deployment. Detection of postconcussive/post-TBI symptoms could facilitate targeting of Army suicide prevention programs.

Prospective associations of perceived unit cohesion with postdeployment mental health outcomes.

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: U.S. 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 were adjusted for sociodemographic and Army service characteristics, predeployment 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; P-values < 0.05). Models of incidence of mental disorders and suicidal ideation among soldiers without these problems predeployment yielded similar results, except that perceived unit cohesion was not associated with incident AUD/SUD. CONCLUSIONS: Soldiers who reported strong unit cohesion before deployment had lower risk of postdeployment mental disorders and suicidal ideation. Awareness of associations of perceived unit cohesion with postdeployment mental health may facilitate targeting of prevention programs.

Genome-wide analyses of psychological resilience in U.S. Army soldiers.

Though a growing body of preclinical and translational research is illuminating a biological basis for resilience to stress, little is known about the genetic basis of psychological resilience in humans. We conducted genome-wide association studies (GWASs) of self-assessed (by questionnaire) and outcome-based (incident mental disorders from predeployment to postdeployment) resilience among European (EUR) ancestry soldiers in the Army study to assess risk and resilience in servicemembers. Self-assessed resilience (N = 11,492) was found to have significant common-variant heritability (h2 = 0.162, se = 0.050, p = 5.37 × 10-4 ), and to be significantly negatively genetically correlated with neuroticism (rg = -0.388, p = .0092). GWAS results from the EUR soldiers revealed a genome-wide significant locus on an intergenic region on Chr 4 upstream from doublecortin-like kinase 2 (DCLK2) (four single nucleotide polymorphisms (SNPs) in LD; top SNP: rs4260523 [p = 5.65 × 10-9 ] is an eQTL in frontal cortex), a member of the doublecortin family of kinases that promote survival and regeneration of injured neurons. A second gene, kelch-like family member 36 (KLHL36) was detected at gene-wise genome-wide significance [p = 1.89 × 10-6 ]. A polygenic risk score derived from the self-assessed resilience GWAS was not significantly associated with outcome-based resilience. In very preliminary results, genome-wide significant association with outcome-based resilience was found for one locus (top SNP: rs12580015 [p = 2.37 × 10-8 ]) on Chr 12 downstream from solute carrier family 15 member 5 (SLC15A5) in subjects (N = 581) exposed to the highest level of deployment stress. The further study of genetic determinants of resilience has the potential to illuminate the molecular bases of stress-related psychopathology and point to new avenues for therapeutic intervention.

Prospective risk factors for post-deployment heavy drinking and alcohol or substance use disorder among US Army soldiers.

BACKGROUND: Investigations of drinking behavior across military deployment cycles are scarce, and few prospective studies have examined risk factors for post-deployment alcohol misuse. METHODS: Prevalence of alcohol misuse was estimated among 4645 US Army soldiers who participated in a longitudinal survey. Assessment occurred 1-2 months before soldiers deployed to Afghanistan in 2012 (T0), upon their return to the USA (T1), 3 months later (T2), and 9 months later (T3). Weights-adjusted logistic regression was used to evaluate associations of hypothesized risk factors with post-deployment incidence and persistence of heavy drinking (HD) (consuming 5 + alcoholic drinks at least 1-2×/week) and alcohol or substance use disorder (AUD/SUD). RESULTS: Prevalence of past-month HD at T0, T2, and T3 was 23.3% (s.e. = 0.7%), 26.1% (s.e. = 0.8%), and 22.3% (s.e. = 0.7%); corresponding estimates for any binge drinking (BD) were 52.5% (s.e. = 1.0%), 52.5% (s.e. = 1.0%), and 41.3% (s.e. = 0.9%). Greater personal life stress during deployment (e.g., relationship, family, or financial problems) - but not combat stress - was associated with new onset of HD at T2 [per standard score increase: adjusted odds ratio (AOR) = 1.20, 95% CI 1.06-1.35, p = 0.003]; incidence of AUD/SUD at T2 (AOR = 1.54, 95% CI 1.25-1.89, p < 0.0005); and persistence of AUD/SUD at T2 and T3 (AOR = 1.30, 95% CI 1.08-1.56, p = 0.005). Any BD pre-deployment was associated with post-deployment onset of HD (AOR = 3.21, 95% CI 2.57-4.02, p < 0.0005) and AUD/SUD (AOR = 1.85, 95% CI 1.27-2.70, p = 0.001). CONCLUSIONS: Alcohol misuse is common during the months preceding and following deployment. Timely intervention aimed at alleviating/managing personal stressors or curbing risky drinking might reduce risk of alcohol-related problems post-deployment.

Predictive validity and correlates of self-assessed resilience among U.S. Army soldiers.

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.

Attention Deficit Hyperactivity Disorder and Risk of Posttraumatic Stress and Related Disorders: A Prospective Longitudinal Evaluation in U.S. Army Soldiers.

Cross-sectional associations between attention deficit hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) have been observed, but longitudinal studies assessing this association are lacking. This prospective study evaluated the association between predeployment ADHD and postdeployment PTSD among U.S. Army soldiers. Soldiers who deployed to Afghanistan were surveyed before deployment (T0) and approximately 1 month (T1), 3 months (T2), and 9 months (T3) after their return. Logistic regression was performed to estimate the association between predeployment ADHD and postdeployment (T2 or T3) PTSD among 4,612 soldiers with data at all waves and no record of stimulant medication treatment during the study. To evaluate specificity of the ADHD-PTSD association, we examined associations among predeployment ADHD, postdeployment major depressive episode (MDE), generalized anxiety disorder (GAD), and suicidal ideation. Weighted prevalence of ADHD predeployment was 6.1% (SE = 0.4%). Adjusting for other risk factors, predeployment ADHD was associated with risk of postdeployment PTSD, adjusted odds ratio (AOR) = 2.13, 95% CI [1.51, 3.00], p < .001, including incidence among soldiers with no predeployment history of PTSD, AOR = 2.50, 95% CI [1.69, 3.69], p < .001. ADHD was associated with postdeployment MDE, AOR = 2.80, 95% CI [2.01, 3.91], p < .001, and GAD, AOR = 3.04, 95% CI [2.10, 4.42], p < .001, but not suicidal ideation. Recognition of associations between predeployment ADHD and postdeployment PTSD, MDE, and GAD may inform targeted prevention efforts. Future research should examine whether treatment of ADHD is protective against PTSD and related disorders in trauma-exposed individuals.

Alcohol Misuse and Co-Occurring Mental Disorders Among New Soldiers in the U.S. Army.

BACKGROUND: Problem drinking that predates enlistment into military service may contribute to the overall burden of alcohol misuse in the Armed Forces; however, evidence bearing on this issue is limited. This study examines prevalence and correlates of alcohol misuse among new U.S. Army soldiers. METHODS: Cross-sectional survey data were collected from soldiers reporting for basic combat training. The survey retrospectively assessed lifetime alcohol consumption and substance abuse/dependence, enabling estimation of the prevalence of lifetime binge drinking and heavy drinking in a sample of 30,583 soldiers and of probable alcohol use disorder (AUD) among 26,754 soldiers with no/minimal lifetime use of other drugs. Co-occurrence of mental disorders and other adverse outcomes with binge drinking, heavy drinking, and AUD was examined. Discrete-time survival analysis, with person-year the unit of analysis and a logistic link function, was used to estimate associations of AUD with subsequent onset of mental disorders and vice versa. RESULTS: Weighted prevalence of lifetime binge drinking was 27.2% (SE = 0.4) among males and 18.9% (SE = 0.7) among females; respective estimates for heavy drinking were 13.9% (SE = 0.3) and 9.4% (SE = 0.4). Among soldiers with no/minimal drug use, 9.5% (SE = 0.2) of males and 7.2% (SE = 0.5) of females had lifetime AUD. Relative to no alcohol misuse, binge drinking, heavy drinking, and AUD were associated with increased odds of all mental disorders and other adverse outcomes under consideration (adjusted odds ratios [AORs] = 1.5 to 4.6; ps < 0.001). Prior mental disorders and suicidal ideation were associated with onset of AUD (AORs = 2.3 to 2.8; ps < 0.001), and prior AUD was associated with onset of mental disorders and suicidal ideation (AORs = 2.0 to 3.2, ps < 0.005). CONCLUSIONS: Strong bidirectional associations between alcohol misuse and mental disorders were observed in a cohort of soldiers beginning Army service. Conjoint recognition of alcohol misuse and mental disorders upon enlistment may provide opportunities for risk mitigation early in a soldier's career.

Associations of childhood bullying victimization with lifetime suicidal behaviors among new U.S. Army soldiers.

BACKGROUND: Prior studies have documented associations of childhood bullying victimization with suicidal behaviors. However, many failed to adjust for concomitant risk factors and none investigated this relationship in military personnel. This study aimed to estimate independent associations of childhood bullying victimization with suicidal behaviors among U.S. Army soldiers. METHODS: Soldiers reporting for basic training completed a cross-sectional survey assessing mental disorders, suicidal behaviors, and childhood adversities including two types of bullying victimization: (1) Physical Assault/Theft and (2) Bullying Comments/Behaviors. Associations of childhood bullying experiences with suicidal behaviors were estimated using discrete-time survival analysis of person-year data from 30,436 soldiers. Models adjusted for sociodemographic factors, childhood maltreatment by adults, and mental disorders. RESULTS: After comprehensive adjustment for other risk factors, more frequent Physical Assault/Theft by peers during childhood was associated with increased odds of lifetime suicidal ideation (adjusted odds ratio [AOR] = 1.18, 95% CI: 1.11-1.26, P < .001) and attempt (AOR = 1.30, 95% CI: 1.13-1.50, P < .001). More frequent Bullying Comments/Behaviors were associated with increased risk of ideation (AOR = 1.30, 95% CI: 1.26-1.35, P < .001), plan (AOR = 1.44, 95% CI: 1.35-1.54, P < .001), attempt (AOR = 1.24, 95% CI: 1.15-1.33, P < .001), and onset of plan among ideators (AOR = 1.09, 95% CI: 1.03-1.15, P = .002). Relative to no bullying victimization, exposure to the most persistent bullying was associated with two- to fourfold increase in risk for suicidal behaviors. CONCLUSIONS: Childhood bullying victimization is associated with lifetime suicidal behaviors among new soldiers. Exposure to Bullying Comments/Behaviors during childhood is associated with progression from suicidal ideation to plan. Improved recognition of these relationships may inform risk mitigation interventions for soldiers.

Improving outcomes for patients with medication-resistant anxiety: effects of collaborative care with cognitive behavioral 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.

Polygenic risk for suicide attempt is associated with lifetime suicide attempt in US soldiers independent of parental risk.

BACKGROUND: Suicide is a leading cause of death worldwide. Whereas some studies have suggested that a direct measure of common genetic liability for suicide attempts (SA), captured by a polygenic risk score for SA (SA-PRS), explains risk independent of parental history, further confirmation would be useful. Even more unsettled is the extent to which SA-PRS is associated with lifetime non-suicidal self-injury (NSSI). METHODS: We used summary statistics from the largest available GWAS study of SA to generate SA-PRS for two non-overlapping cohorts of soldiers of European ancestry. These were tested in multivariable models that included parental major depressive disorder (MDD) and parental SA. RESULTS: In the first cohort, 417 (6.3 %) of 6573 soldiers reported lifetime SA and 1195 (18.2 %) reported lifetime NSSI. In a multivariable model that included parental history of MDD and parental history of SA, SA-PRS remained significantly associated with lifetime SA [aOR = 1.26, 95%CI:1.13-1.39, p < 0.001] per standardized unit SA-PRS]. In the second cohort, 204 (4.2 %) of 4900 soldiers reported lifetime SA, and 299 (6.1 %) reported lifetime NSSI. In a multivariable model that included parental history of MDD and parental history of SA, SA-PRS remained significantly associated with lifetime SA [aOR = 1.20, 95%CI:1.04-1.38, p = 0.014]. A combined analysis of both cohorts yielded similar results. In neither cohort or in the combined analysis was SA-PRS significantly associated with NSSI. CONCLUSIONS: PRS for SA conveys information about likelihood of lifetime SA (but not NSSI, demonstrating specificity), independent of self-reported parental history of MDD and parental history of SA. LIMITATIONS: At present, the magnitude of effects is small and would not be immediately useful for clinical decision-making or risk-stratified prevention initiatives, but this may be expected to improve with further iterations. Also critical will be the extension of these findings to more diverse populations.

Effects of medical comorbidity on anxiety treatment outcomes in primary care.

OBJECTIVE: To evaluate the effects of medical comorbidity on anxiety treatment outcomes. METHODS: Data were analyzed from 1004 primary care patients enrolled in a trial of a collaborative care intervention for anxiety. Linear-mixed models accounting for baseline characteristics were used to evaluate the effects of overall medical comorbidity (two or more chronic medical conditions [CMCs] versus fewer than two CMCs) and specific CMCs (migraine, asthma, and gastrointestinal disease) on anxiety treatment outcomes at 6, 12, and 18 months. RESULTS: At baseline, patients with two or more CMCs (n = 582; 58.0%) reported more severe anxiety symptoms (10.5 [95% confidence interval {CI} = 10.1-10.9] versus 9.5 [95% CI = 9.0-10.0], p = .003) and anxiety-related disability (17.6 [95% CI = 17.0-18.2] versus 16.0 [95% CI = 15.3-16.7], p = .001). However, their clinical improvement was comparable to that of patients with one or zero CMCs (predicted change in anxiety symptoms = -3.9 versus -4.1 at 6 months, -4.6 versus -4.4 at 12 months, -4.9 versus -5.0 at 18 months; predicted change in anxiety-related disability = -6.4 versus -6.9 at 6 months, -6.9 versus -7.3 at 12 months, -7.3 versus -7.5 at 18 months). The only specific CMC with a detrimental effect was migraine, which was associated with less improvement in anxiety symptoms at 18 months (predicted change = -4.1 versus -5.3). CONCLUSIONS: Effectiveness of the anxiety intervention was not significantly affected by the presence of multiple CMCs; however, patients with migraine displayed less improvement at long-term follow-up. Trial Registration ClinicalTrials.com Identifier: NCT00347269.