A genome-wide gene-by-trauma interaction study of alcohol misuse in two independent cohorts identifies PRKG1 as a risk locus.

Traumatic life experiences are associated with alcohol use problems, an association that is likely to be moderated by genetic predisposition. To understand these interactions, we conducted a gene-by-environment genome-wide interaction study (GEWIS) of alcohol use problems in two independent samples, the Army STARRS (STARRS, N=16 361) and the Yale-Penn (N=8084) cohorts. Because the two cohorts were assessed using different instruments, we derived separate dimensional alcohol misuse scales and applied a proxy-phenotype study design. In African-American subjects, we identified an interaction of PRKG1 rs1729578 with trauma exposure in the STARRS cohort and replicated its interaction with trauma exposure in the Yale-Penn cohort (discovery-replication meta-analysis: z=5.64, P=1.69 × 10-8). PRKG1 encodes cyclic GMP-dependent protein kinase 1, which is involved in learning, memory and circadian rhythm regulation. Considering the loci identified in stage-1 that showed same effect directions in stage-2, the gene ontology (GO) enrichment analysis showed several significant results, including calcium-activated potassium channels (GO:0016286; P=2.30 × 10-5), cognition (GO:0050890; P=1.90 × 10-6), locomotion (GO:0040011; P=6.70 × 10-5) and Stat3 protein regulation (GO:0042517; P=6.4 × 10-5). To our knowledge, this is the largest GEWIS performed in psychiatric genetics, and the first GEWIS examining risk for alcohol misuse. Our results add to a growing body of literature highlighting the dynamic impact of experience on individual genetic risk.

Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability.

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

Predicting suicides after outpatient mental health visits in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS).

The 2013 US Veterans Administration/Department of Defense Clinical Practice Guidelines (VA/DoD CPG) require comprehensive suicide risk assessments for VA/DoD patients with mental disorders but provide minimal guidance on how to carry out these assessments. Given that clinician-based assessments are not known to be strong predictors of suicide, we investigated whether a precision medicine model using administrative data after outpatient mental health specialty visits could be developed to predict suicides among outpatients. We focused on male nondeployed Regular US Army soldiers because they account for the vast majority of such suicides. Four machine learning classifiers (naive Bayes, random forests, support vector regression and elastic net penalized regression) were explored. Of the Army suicides in 2004-2009, 41.5% occurred among 12.0% of soldiers seen as outpatient by mental health specialists, with risk especially high within 26 weeks of visits. An elastic net classifier with 10-14 predictors optimized sensitivity (45.6% of suicide deaths occurring after the 15% of visits with highest predicted risk). Good model stability was found for a model using 2004-2007 data to predict 2008-2009 suicides, although stability decreased in a model using 2008-2009 data to predict 2010-2012 suicides. The 5% of visits with highest risk included only 0.1% of soldiers (1047.1 suicides/100 000 person-years in the 5 weeks after the visit). This is a high enough concentration of risk to have implications for targeting preventive interventions. An even better model might be developed in the future by including the enriched information on clinician-evaluated suicide risk mandated by the VA/DoD CPG to be recorded.

Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers.

OBJECTIVE: To investigate whether trauma exposure moderates the genetic correlation between substance use disorders and psychiatric disorders, we tested whether trauma exposure modifies the association of genetic risks for mental disorders with alcohol misuse and nicotine dependence (ND) symptoms. METHODS: High-resolution polygenic risk scores (PRSs) were calculated for 10 732 US Army soldiers (8346 trauma-exposed and 2386 trauma-unexposed) based on genome-wide association studies of bipolar disorder (BD), major depressive disorder, and schizophrenia. RESULTS: The main finding was a significant BD PRS-by-trauma interaction with respect to alcohol misuse (P = 6.07 × 10-3 ). We observed a positive correlation between BD PRS and alcohol misuse in trauma-exposed soldiers (r = 0.029, P = 7.5 × 10-3 ) and a negative correlation in trauma-unexposed soldiers (r = -0.071, P = 5.61 × 10-4 ). Consistent (nominally significant) result with concordant effect, directions were observed in the schizophrenia PRS-by-trauma interaction analysis. The variants included in the BD PRS-by-trauma interaction showed significant enrichments for gene ontologies related to high voltage-gated calcium channel activity (GO:0008331, P = 1.51 × 10-5 ; GO:1990454, P = 4.49 × 10-6 ; GO:0030315, P = 2.07 × 10-6 ) and for Beta1/Beta2 adrenergic receptor signaling pathways (P = 2.61 × 10-4 ). CONCLUSIONS: These results indicate that the genetic overlap between alcohol misuse and BD is significantly moderated by trauma exposure. This provides molecular insight into the complex mechanisms that link substance abuse, psychiatric disorders, and trauma exposure.

Childhood adversity, adult stress, and the risk of major depression or generalized anxiety disorder in US soldiers: a test of the stress sensitization hypothesis.

BACKGROUND: The stress sensitization theory hypothesizes that individuals exposed to childhood adversity will be more vulnerable to mental disorders from proximal stressors. We aimed to test this theory with respect to risk of 30-day major depressive episode (MDE) and generalized anxiety disorder (GAD) among new US Army soldiers. METHODS: The sample consisted of 30 436 new soldier recruits in the Army Study to Assess Risk and Resilience (Army STARRS). Generalized linear models were constructed, and additive interactions between childhood maltreatment profiles and level of 12-month stressful experiences on the risk of 30-day MDE and GAD were analyzed. RESULTS: Stress sensitization was observed in models of past 30-day MDE (χ2 8 = 17.6, p = 0.025) and GAD (χ2 8 = 26.8, p = 0.001). This sensitization only occurred at high (3+) levels of reported 12-month stressful experiences. In pairwise comparisons for the risk of 30-day MDE, the risk difference between 3+ stressful experiences and no stressful experiences was significantly greater for all maltreatment profiles relative to No Maltreatment. Similar results were found with the risk for 30-day GAD with the exception of the risk difference for Episodic Emotional and Sexual Abuse, which did not differ statistically from No Maltreatment. CONCLUSIONS: New soldiers are at an increased risk of 30-day MDE or GAD following recent stressful experiences if they were exposed to childhood maltreatment. Particularly in the military with an abundance of unique stressors, attempts to identify this population and improve stress management may be useful in the effort to reduce the risk of mental disorders.

Psychological autopsy study comparing suicide decedents, suicide ideators, and propensity score matched controls: results from the study to assess risk and resilience in service members (Army STARRS).

BACKGROUND: The suicide rate has increased significantly among US Army soldiers over the past decade. Here we report the first results from a large psychological autopsy study using two control groups designed to reveal risk factors for suicide death among soldiers beyond known sociodemographic factors and the presence of suicide ideation. METHODS: Informants were next-of-kin and Army supervisors for: 135 suicide cases, 137 control soldiers propensity-score-matched on known sociodemographic risk factors for suicide and Army history variables, and 118 control soldiers who reported suicide ideation in the past year. RESULTS: Results revealed that most (79.3%) soldiers who died by suicide have a prior mental disorder; mental disorders in the prior 30-days were especially strong risk factors for suicide death. Approximately half of suicide decedents tell someone that they are considering suicide. Virtually all of the risk factors identified in this study differed between suicide cases and propensity-score-matched controls, but did not significantly differ between suicide cases and suicide ideators. The most striking difference between suicides and ideators was the presence in the former of an internalizing disorder (especially depression) and multi-morbidity (i.e. 3+ disorders) in the past 30 days. CONCLUSIONS: Most soldiers who die by suicide have identifiable mental disorders shortly before their death and tell others about their suicidal thinking, suggesting that there are opportunities for prevention and intervention. However, few risk factors distinguish between suicide ideators and decedents, pointing to an important direction for future research.

Using self-report surveys at the beginning of service to develop multi-outcome risk models for new soldiers in the U.S. Army.

BACKGROUND: The U.S. Army uses universal preventives interventions for several negative outcomes (e.g. suicide, violence, sexual assault) with especially high risks in the early years of service. More intensive interventions exist, but would be cost-effective only if targeted at high-risk soldiers. We report results of efforts to develop models for such targeting from self-report surveys administered at the beginning of Army service. METHODS: 21 832 new soldiers completed a self-administered questionnaire (SAQ) in 2011-2012 and consented to link administrative data to SAQ responses. Penalized regression models were developed for 12 administratively-recorded outcomes occurring by December 2013: suicide attempt, mental hospitalization, positive drug test, traumatic brain injury (TBI), other severe injury, several types of violence perpetration and victimization, demotion, and attrition. RESULTS: The best-performing models were for TBI (AUC = 0.80), major physical violence perpetration (AUC = 0.78), sexual assault perpetration (AUC = 0.78), and suicide attempt (AUC = 0.74). Although predicted risk scores were significantly correlated across outcomes, prediction was not improved by including risk scores for other outcomes in models. Of particular note: 40.5% of suicide attempts occurred among the 10% of new soldiers with highest predicted risk, 57.2% of male sexual assault perpetrations among the 15% with highest predicted risk, and 35.5% of female sexual assault victimizations among the 10% with highest predicted risk. CONCLUSIONS: Data collected at the beginning of service in self-report surveys could be used to develop risk models that define small proportions of new soldiers accounting for high proportions of negative outcomes over the first few years of service.

Inter-site and inter-scanner diffusion MRI data harmonization.

We propose a novel method to harmonize diffusion MRI data acquired from multiple sites and scanners, which is imperative for joint analysis of the data to significantly increase sample size and statistical power of neuroimaging studies. Our method incorporates the following main novelties: i) we take into account the scanner-dependent spatial variability of the diffusion signal in different parts of the brain; ii) our method is independent of compartmental modeling of diffusion (e.g., tensor, and intra/extra cellular compartments) and the acquired signal itself is corrected for scanner related differences; and iii) inter-subject variability as measured by the coefficient of variation is maintained at each site. We represent the signal in a basis of spherical harmonics and compute several rotation invariant spherical harmonic features to estimate a region and tissue specific linear mapping between the signal from different sites (and scanners). We validate our method on diffusion data acquired from seven different sites (including two GE, three Philips, and two Siemens scanners) on a group of age-matched healthy subjects. Since the extracted rotation invariant spherical harmonic features depend on the accuracy of the brain parcellation provided by Freesurfer, we propose a feature based refinement of the original parcellation such that it better characterizes the anatomy and provides robust linear mappings to harmonize the dMRI data. We demonstrate the efficacy of our method by statistically comparing diffusion measures such as fractional anisotropy, mean diffusivity and generalized fractional anisotropy across multiple sites before and after data harmonization. We also show results using tract-based spatial statistics before and after harmonization for independent validation of the proposed methodology. Our experimental results demonstrate that, for nearly identical acquisition protocol across sites, scanner-specific differences can be accurately removed using the proposed method.

Early life stress and the anxious brain: evidence for a neural mechanism linking childhood emotional maltreatment to anxiety in adulthood.

BACKGROUND: Childhood emotional maltreatment (CEM) increases the likelihood of developing an anxiety disorder in adulthood, but the neural processes underlying conferment of this risk have not been established. Here, we test the potential for neuroimaging the adult brain to inform understanding of the mechanism linking CEM to adult anxiety symptoms. METHOD: One hundred eighty-two adults (148 females, 34 males) with a normal-to-clinical range of anxiety symptoms underwent structural and functional magnetic resonance imaging while completing an emotion-processing paradigm with facial expressions of fear, anger, and happiness. Participants completed self-report measures of CEM and current anxiety symptoms. Voxelwise mediation analyses on gray-matter volumes and activation to each emotion condition were used to identify candidate brain mechanisms relating CEM to anxiety in adulthood. RESULTS: During processing of fear and anger faces, greater amygdala and less right dorsolateral prefrontal (dlPFC) activation partially mediated the positive relationship between CEM and anxiety symptoms. Greater right posterior insula activation to fear also partially mediated this relationship, as did greater ventral anterior cingulate (ACC) and less dorsal ACC activation to anger. Responses to happy faces in these regions did not mediate the CEM-anxiety relationship. Smaller right dlPFC gray-matter volumes also partially mediated the CEM-anxiety relationship. CONCLUSIONS: Activation patterns of the adult brain demonstrate the potential to inform mechanistic accounts of the CEM conferment of anxiety symptoms. Results support the hypothesis that exaggerated limbic activation to negative valence facial emotions links CEM to anxiety symptoms, which may be consequent to a breakdown of cortical regulatory processes.

Predicting non-familial major physical violent crime perpetration in the US Army from administrative data.

BACKGROUND: Although interventions exist to reduce violent crime, optimal implementation requires accurate targeting. We report the results of an attempt to develop an actuarial model using machine learning methods to predict future violent crimes among US Army soldiers. METHOD: A consolidated administrative database for all 975 057 soldiers in the US Army in 2004-2009 was created in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). Of these soldiers, 5771 committed a first founded major physical violent crime (murder-manslaughter, kidnapping, aggravated arson, aggravated assault, robbery) over that time period. Temporally prior administrative records measuring socio-demographic, Army career, criminal justice, medical/pharmacy, and contextual variables were used to build an actuarial model for these crimes separately among men and women using machine learning methods (cross-validated stepwise regression, random forests, penalized regressions). The model was then validated in an independent 2011-2013 sample. RESULTS: Key predictors were indicators of disadvantaged social/socioeconomic status, early career stage, prior crime, and mental disorder treatment. Area under the receiver-operating characteristic curve was 0.80-0.82 in 2004-2009 and 0.77 in the 2011-2013 validation sample. Of all administratively recorded crimes, 36.2-33.1% (male-female) were committed by the 5% of soldiers having the highest predicted risk in 2004-2009 and an even higher proportion (50.5%) in the 2011-2013 validation sample. CONCLUSIONS: Although these results suggest that the models could be used to target soldiers at high risk of violent crime perpetration for preventive interventions, final implementation decisions would require further validation and weighing of predicted effectiveness against intervention costs and competing risks.

Telephone Problem-Solving Treatment Improves Sleep Quality in Service Members With Combat-Related Mild Traumatic Brain Injury: Results From a Randomized Clinical Trial.

OBJECTIVE: Evaluate sleep quality, its correlates, and the effect of telephone-based problem-solving treatment (PST) in active duty postdeployment service members with mild traumatic brain injury (mTBI) SETTING:: Randomized clinical trial. PARTICIPANTS: Active duty service members with combat-related mTBI. STUDY DESIGN: Education-only (EO) and PST groups (N = 178 each) received printed study materials and 12 educational brochures. The PST group additionally received up to 12 PST telephone calls addressing participant-selected issues. Outcomes were evaluated postintervention (6 months) and at 12 months. MAIN MEASURE: Pittsburgh Sleep Quality Index. RESULTS: Sleep quality was manifestly poor in both groups at baseline (Pittsburgh Sleep Quality Index = 12.5 ± 4). Overall sleep quality was significantly different between the PST and EO groups at 6 months (P = .003) but not at 12 months. Longitudinally, PST significantly improved sleep quality at 6 months (P = .001) but not over the follow-up. Low sleep quality was associated with concussion symptoms, pain, depression, and posttraumatic stress disorder at all time points (P < .0001). CONCLUSIONS: Sleep disorders, common in postdeployment service members with mTBI, are strongly associated with the presence of pain, posttraumatic stress disorder, and depression. Telephone-based PST may be an effective therapeutic approach for reducing sleep disorders in this population. Research should focus on maintenance of treatment gains.

An examination of the bidirectional relationship between functioning and symptom levels in patients with anxiety disorders in the CALM study.

BACKGROUND: Patients with anxiety disorders suffer marked functional impairment in their activities of daily living. Many studies have documented that improvements in anxiety symptom severity predict functioning improvements. However, no studies have investigated how improvements in functioning simultaneously predict symptom reduction. We hypothesized that symptom levels at a given time point will predict functioning at the subsequent time point, and simultaneously that functioning at a given time point will predict symptom levels at a subsequent time point. METHOD: Patients were recruited from primary-care centers for the Coordinated Anxiety Learning and Management (CALM) study and were randomized to receive either computer-assisted cognitive-behavioral therapy and/or medication management (ITV) or usual care (UC). A cross-lagged panel design examined the relationship between functional impairment and anxiety and depression symptom severity at baseline, 6-, 12-, and 18-month follow-up assessments. RESULTS: Prospective prediction of functioning from symptoms and symptoms from functioning were both important in modeling these associations. Anxiety and depression predicted functioning as strongly as functioning predicted anxiety and depression. There were some differences in these associations between UC and ITV. Where differences emerged, the UC group was best modeled with prospective paths predicting functioning from symptoms, whereas symptoms and functioning were both important predictors in the ITV group. CONCLUSIONS: Treatment outcome is best captured by measures of functional impairment as well as symptom severity. Implications for treatment are discussed, as well as future directions of research.

Understanding the elevated suicide risk of female soldiers during deployments.

BACKGROUND: The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) has found that the proportional elevation in the US Army enlisted soldier suicide rate during deployment (compared with the never-deployed or previously deployed) is significantly higher among women than men, raising the possibility of gender differences in the adverse psychological effects of deployment. METHOD: Person-month survival models based on a consolidated administrative database for active duty enlisted Regular Army soldiers in 2004-2009 (n = 975,057) were used to characterize the gender × deployment interaction predicting suicide. Four explanatory hypotheses were explored involving the proportion of females in each soldier's occupation, the proportion of same-gender soldiers in each soldier's unit, whether the soldier reported sexual assault victimization in the previous 12 months, and the soldier's pre-deployment history of treated mental/behavioral disorders. RESULTS: The suicide rate of currently deployed women (14.0/100,000 person-years) was 3.1-3.5 times the rates of other (i.e. never-deployed/previously deployed) women. The suicide rate of currently deployed men (22.6/100,000 person-years) was 0.9-1.2 times the rates of other men. The adjusted (for time trends, sociodemographics, and Army career variables) female:male odds ratio comparing the suicide rates of currently deployed v. other women v. men was 2.8 (95% confidence interval 1.1-6.8), became 2.4 after excluding soldiers with Direct Combat Arms occupations, and remained elevated (in the range 1.9-2.8) after adjusting for the hypothesized explanatory variables. CONCLUSIONS: These results are valuable in excluding otherwise plausible hypotheses for the elevated suicide rate of deployed women and point to the importance of expanding future research on the psychological challenges of deployment for women.

Occupational differences in US Army suicide rates.

BACKGROUND: Civilian suicide rates vary by occupation in ways related to occupational stress exposure. Comparable military research finds suicide rates elevated in combat arms occupations. However, no research has evaluated variation in this pattern by deployment history, the indicator of occupation stress widely considered responsible for the recent rise in the military suicide rate. METHOD: The joint associations of Army occupation and deployment history in predicting suicides were analysed in an administrative dataset for the 729 337 male enlisted Regular Army soldiers in the US Army between 2004 and 2009. RESULTS: There were 496 suicides over the study period (22.4/100 000 person-years). Only two occupational categories, both in combat arms, had significantly elevated suicide rates: infantrymen (37.2/100 000 person-years) and combat engineers (38.2/100 000 person-years). However, the suicide rates in these two categories were significantly lower when currently deployed (30.6/100 000 person-years) than never deployed or previously deployed (41.2-39.1/100 000 person-years), whereas the suicide rate of other soldiers was significantly higher when currently deployed and previously deployed (20.2-22.4/100 000 person-years) than never deployed (14.5/100 000 person-years), resulting in the adjusted suicide rate of infantrymen and combat engineers being most elevated when never deployed [odds ratio (OR) 2.9, 95% confidence interval (CI) 2.1-4.1], less so when previously deployed (OR 1.6, 95% CI 1.1-2.1), and not at all when currently deployed (OR 1.2, 95% CI 0.8-1.8). Adjustment for a differential 'healthy warrior effect' cannot explain this variation in the relative suicide rates of never-deployed infantrymen and combat engineers by deployment status. CONCLUSIONS: Efforts are needed to elucidate the causal mechanisms underlying this interaction to guide preventive interventions for soldiers at high suicide risk.

Sociodemographic and career history predictors of suicide mortality in the United States Army 2004-2009.

BACKGROUND: The US Army suicide rate has increased sharply in recent years. Identifying significant predictors of Army suicides in Army and Department of Defense (DoD) administrative records might help focus prevention efforts and guide intervention content. Previous studies of administrative data, although documenting significant predictors, were based on limited samples and models. A career history perspective is used here to develop more textured models. METHOD: The analysis was carried out as part of the Historical Administrative Data Study (HADS) of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). De-identified data were combined across numerous Army and DoD administrative data systems for all Regular Army soldiers on active duty in 2004-2009. Multivariate associations of sociodemographics and Army career variables with suicide were examined in subgroups defined by time in service, rank and deployment history. RESULTS: Several novel results were found that could have intervention implications. The most notable of these were significantly elevated suicide rates (69.6-80.0 suicides per 100 000 person-years compared with 18.5 suicides per 100 000 person-years in the total Army) among enlisted soldiers deployed either during their first year of service or with less than expected (based on time in service) junior enlisted rank; a substantially greater rise in suicide among women than men during deployment; and a protective effect of marriage against suicide only during deployment. CONCLUSIONS: A career history approach produces several actionable insights missed in less textured analyses of administrative data predictors. Expansion of analyses to a richer set of predictors might help refine understanding of intervention implications.

Prefrontal dysfunction during emotion regulation in generalized anxiety and panic disorders.

BACKGROUND: The mechanisms that contribute to emotion dysregulation in anxiety disorders are not well understood. Two common disorders, generalized anxiety disorder (GAD) and panic disorder (PD), were examined to test the hypothesis that both disorders are characterized by hypo-activation in prefrontal cortex (PFC) during emotion regulation. A competing hypothesis that GAD in particular is characterized by PFC hyper-activation during emotion regulation (reflecting overactive top-down control) was also evaluated. Method Twenty-two medication-free healthy control (HC), 23 GAD, and 18 PD participants underwent functional magnetic resonance imaging (fMRI) during a task that required them to reappraise (i.e. reduce) or maintain emotional responses to negative images. RESULTS: GAD participants reported the least reappraisal use in daily life, and reappraisal use was inversely associated with anxiety severity and functional impairment in these participants. During fMRI, HCs demonstrated greater activation during both reappraisal and maintenance than either GAD or PD participants (who did not differ) in brain areas important for emotion regulation (e.g. dorsolateral and dorsomedial PFC). Furthermore, across all anxious participants, activation during reappraisal in dorsolateral and dorsomedial PFC was inversely associated with anxiety severity and functional impairment. CONCLUSIONS: Emotion dysregulation in GAD and PD may be the consequence of PFC hypo-activation during emotion regulation, consistent with insufficient top-down control. The relationship between PFC hypo-activation and functional impairment suggests that the failure to engage PFC during emotion regulation may be part of the critical transition from dispositionally high anxiety to an anxiety disorder.

Adverse childhood experiences in relation to mood and anxiety disorders in a population-based sample of active military personnel.

BACKGROUND: Although it has been posited that exposure to adverse childhood experiences (ACEs) increases vulnerability to deployment stress, previous literature in this area has demonstrated conflicting results. Using a cross-sectional population-based sample of active military personnel, the present study examined the relationship between ACEs, deployment related stressors and mood and anxiety disorders. METHOD: Data were analyzed from the 2002 Canadian Community Health Survey-Canadian Forces Supplement (CCHS-CFS; n = 8340, age 18-54 years, response rate 81%). The following ACEs were self-reported retrospectively: childhood physical abuse, childhood sexual abuse, economic deprivation, exposure to domestic violence, parental divorce/separation, parental substance abuse problems, hospitalization as a child, and apprehension by a child protection service. DSM-IV mood and anxiety disorders [major depressive disorder, post-traumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic attacks/disorder and social phobia] were assessed using the composite international diagnostic interview (CIDI). RESULTS: Even after adjusting for the effects of deployment-related traumatic exposures (DRTEs), exposure to ACEs was significantly associated with past-year mood or anxiety disorder among men [adjusted odds ratio (aOR) 1.34, 99% confidence interval (CI) 1.03-1.73, p < 0.01] and women [aOR 1.37, 99% CI 1.00-1.89, p = 0.01]. Participants exposed to both ACEs and DRTEs had the highest prevalence of past-year mood or anxiety disorder in comparison to those who were exposed to either ACEs alone, DRTEs alone, or no exposure. CONCLUSIONS: ACEs are associated with several mood and anxiety disorders among active military personnel. Intervention strategies to prevent mental health problems should consider the utility of targeting soldiers with exposure to ACEs.

Common mental disorder diagnosis and need for treatment are not the same: findings from a population-based longitudinal survey.

BACKGROUND: Controversy exists regarding whether people in the community who meet criteria for a non-psychotic mental disorder diagnosis are necessarily in need of treatment. Some have argued that these individuals require treatment and that policy makers need to develop outreach programs for them, whereas others have argued that the current epidemiologic studies may be diagnosing symptoms of distress that in many cases are self-limiting and likely to remit without treatment. All prior studies that have addressed this issue have been cross-sectional. We examined the longitudinal outcomes of individuals with depressive, anxiety and substance use (DAS) disorder(s) who had not previously received any treatment. Method Data came from a nationally representative US sample. A total of 34 653 non-institutionalized adults (age ≥20 years) were interviewed at two time points, 3 years apart. DAS disorders, mental health service use and quality of life (QoL) were assessed at both time points. RESULTS: Individuals with a DAS disorder who had not previously received any treatment were significantly more likely than those who had been previously treated to have remission of their index disorder(s) without subsequent treatment, to be free of co-morbid disorder(s) and not to have attempted suicide during the 3-year follow-up period (50.7% v. 33.0% respectively, p < 0.05). At wave 2, multiple linear regression demonstrated that people with a remission of their baseline DAS disorder(s) had levels of functioning similar to those without a DAS disorder. CONCLUSIONS: Individuals with an untreated DAS disorder at baseline have a substantial likelihood of remission without any subsequent intervention.

Composite International Diagnostic Interview screening scales for DSM-IV anxiety and mood disorders.

BACKGROUND: Lack of coordination between screening studies for common mental disorders in primary care and community epidemiological samples impedes progress in clinical epidemiology. Short screening scales based on the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI), the diagnostic interview used in community epidemiological surveys throughout the world, were developed to address this problem. METHOD: Expert reviews and cognitive interviews generated CIDI screening scale (CIDI-SC) item pools for 30-day DSM-IV-TR major depressive episode (MDE), generalized anxiety disorder (GAD), panic disorder (PD) and bipolar disorder (BPD). These items were administered to 3058 unselected patients in 29 US primary care offices. Blinded SCID clinical reinterviews were administered to 206 of these patients, oversampling screened positives. RESULTS: Stepwise regression selected optimal screening items to predict clinical diagnoses. Excellent concordance [area under the receiver operating characteristic curve (AUC)] was found between continuous CIDI-SC and DSM-IV/SCID diagnoses of 30-day MDE (0.93), GAD (0.88), PD (0.90) and BPD (0.97), with only 9-38 questions needed to administer all scales. CIDI-SC versus SCID prevalence differences are insignificant at the optimal CIDI-SC diagnostic thresholds (χ2 1 = 0.0-2.9, p = 0.09-0.94). Individual-level diagnostic concordance at these thresholds is substantial (AUC 0.81-0.86, sensitivity 68.0-80.2%, specificity 90.1-98.8%). Likelihood ratio positive (LR+) exceeds 10 and LR- is 0.1 or less at informative thresholds for all diagnoses. CONCLUSIONS: CIDI-SC operating characteristics are equivalent (MDE, GAD) or superior (PD, BPD) to those of the best alternative screening scales. CIDI-SC results can be compared directly to general population CIDI survey results or used to target and streamline second-stage CIDIs.

Incremental benefits and cost of coordinated anxiety learning and management for anxiety treatment in primary care.

BACKGROUND: Improving the quality of mental health care requires integrating successful research interventions into 'real-world' practice settings. Coordinated Anxiety Learning and Management (CALM) is a treatment-delivery model for anxiety disorders encountered in primary care. CALM offers cognitive behavioral therapy (CBT), medication, or both; non-expert care managers assisting primary care clinicians with adherence promotion and medication optimization; computer-assisted CBT delivery; and outcome monitoring. This study describes incremental benefits, costs and net benefits of CALM versus usual care (UC). METHOD: The CALM randomized, controlled effectiveness trial was conducted in 17 primary care clinics in four US cities from 2006 to 2009. Of 1062 eligible patients, 1004 English- or Spanish-speaking patients aged 18-75 years with panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD) and/or post-traumatic stress disorder (PTSD) with or without major depression were randomized. Anxiety-free days (AFDs), quality-adjusted life years (QALYs) and expenditures for out-patient visits, emergency room (ER) visits, in-patient stays and psychiatric medications were estimated based on blinded telephone assessments at baseline, 6, 12 and 18 months. RESULTS: Over 18 months, CALM participants, on average, experienced 57.1 more AFDs [95% confidence interval (CI) 31-83] and $245 additional medical expenses (95% CI $-733 to $1223). The mean incremental net benefit (INB) of CALM versus UC was positive when an AFD was valued ≥$4. For QALYs based on the Short-Form Health Survey-12 (SF-12) and the EuroQol EQ-5D, the mean INB was positive at ≥$5000. CONCLUSIONS: Compared with UC, CALM provides significant benefits with modest increases in health-care expenditures.