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Recently developed measures of genetic liability to suicide attempt may convey unique information regarding an individuals risk of suicidal behavior. We calculated a polygenic risk score for suicide attempt (SA-PRS) for soldiers of European ancestry who participated in the Army STARRS New Soldier Study (NSS; n = 6573) or Pre/Post Deployment Study (PPDS; n = 4900). Multivariable logistic regression models were fit within each sample to estimate the association of SA-PRS with lifetime suicide attempt (LSA), and to examine whether SA-PRS displayed additive or interactive effects with environmental and behavioral risk/protective factors (lifetime trauma burden, childhood maltreatment, negative urgency impulsivity, social network size, perceived mattering, and dispositional optimism). Age, sex, and within-ancestry variation were included as covariates. Observed prevalence of LSA was 6.3% and 4.2% in the NSS and PPDS samples, respectively. In the NSS model, SA-PRS and environmental/behavioral factors displayed strictly additive effects on odds of LSA. Results indicated an estimated 21% increase in odds of LSA per 1 SD increase in SA-PRS [adjusted odds ratio (AOR; 95% CI) = 1.21 (1.09-1.35)]. In PPDS, the effect of SA-PRS varied by reports of optimism [AOR = 0.85 (0.74-0.98) for SA-PRS x optimism effect]. Individuals reporting low and average optimism had 37% and 16% increased odds of LSA per 1 SD increase in SA-PRS, respectively, whereas SA-PRS was not associated with LSA in those reporting high optimism. Overall, results suggested the SA-PRS had predictive value over and above several environmental and behavioral risk factors for LSA. Moreover, elevated SA-PRS may be more concerning in the presence of environmental and behavioral risk factors (e.g., high trauma burden; low optimism). Given the relatively small effect magnitudes, the cost and incremental benefits of utilizing SA-PRS for risk targeting must also be considered in future work.

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.

BACKGROUND: The combination of unhealthy alcohol use and depression is associated with adverse outcomes including higher rates of alcohol use disorder and poorer depression course. Therefore, addressing alcohol use among individuals with depression may have a substantial public health impact. We compared the effectiveness of a brief intervention (BI) for unhealthy alcohol use among patients with and without depression. METHOD: This observational study included 312,056 adult primary care patients at Kaiser Permanente Northern California who screened positive for unhealthy drinking between 2014 and 2017. Approximately half (48%) received a BI for alcohol use and 9% had depression. We examined 12-month changes in heavy drinking days in the previous three months, drinking days per week, drinks per drinking day, and drinks per week. Machine learning was used to estimate BI propensity, follow-up participation, and alcohol outcomes for an augmented inverse probability weighting (AIPW) estimator of the average treatment (BI) effect. This approach does not depend on the strong parametric assumptions of traditional logistic regression, making it more robust to model misspecification. RESULTS: BI had a significant effect on each alcohol use outcome in the non-depressed subgroup (-0.41 to -0.05, all ps  .28). However, differences between subgroups were nonsignificant (0.00 to 0.11, all ps > .44). CONCLUSION: On average, BI is an effective approach to reducing unhealthy drinking, but more research is necessary to understand its impact on patients with depression. AIPW with machine learning provides a robust method for comparing intervention effectiveness across subgroups.

We conducted a systematic review and network meta-analyses (NMA) of psychotherapy and pharmacologic treatments for individuals with co-occurring posttraumatic stress disorder (PTSD) and alcohol or other drug use disorder (AOD). A comprehensive search spanning 1995–2019 yielded a pool of 39 studies for systematic review, including 24 randomized controlled trials for the NMA. Study interventions were grouped by target of treatment (PTSD + AOD, PTSD-only, and AOD-only) and approach (psychotherapy or medication). Standardized mean differences (SMD) from the NMA yielded evidence that at the end of treatment, integrated, trauma-focused therapy for PTSD + AOD was more effective at reducing PTSD symptoms than integrated, non-trauma-focused therapy (SMD = −0.30), AOD-focused psychotherapy (SMD = −0.29), and other control psychotherapies (SMD = −0.43). End-of-treatment alcohol use severity was less for AOD medication compared to placebo medication (SMD = −0.36) and trauma-focused therapy for PTSD + placebo medication (SMD = −0.67), and less for trauma-focused psychotherapy + AOD medication compared to PTSD medication (SMD = −0.53), placebo medication (SMD = −0.50), and trauma-focused psychotherapy + placebo medication (SMD = −0.81). Key limitations include the small number of studies in the NMA for pharmacologic treatments and the lack of demographic diversity apparent in the existing literature. Findings suggest room for new studies that can address limitations in study sample composition, sample sizes, retention, and apply new techniques for conducting comparative effectiveness in PTSD + AOD treatment. Public Significance Statement: Roughly half of individuals with posttraumatic stress disorder (PTSD) also meet the criteria for an alcohol and other drug use disorder (AOD) with numerous and costly public health consequences. A systematic review and network meta-analysis characterized the evidence base of psychotherapy and pharmacological interventions for PTSD and AOD. Integrated, trauma-focused interventions targeting both PTSD and AOD were more effective at reducing PTSD symptoms than integrated non-trauma-focused, AOD-focused psychotherapy, and other control psychotherapies. AOD medications with and without trauma-focused therapies were more effective in reducing alcohol use severity than placebo controls. Few treatment studies reported adverse events for any intervention outcomes. [ABSTRACT FROM AUTHOR]