Phenotypic predictors of suicide subtypes from pre-to postdeployment in active duty military personnel.

Military service members are at increased risk for suicide, but there are few strategies for detecting those who are at highest risk after a deployment. Using all available data collected from 4119 Military service members before and after their deployment to Iraq for Operation Iraqi Freedom, we tested whether predeployment characteristics clustered together to predict postdeployment suicidal risk. Latent class analysis showed that three classes best characterized the sample at predeployment. Class 1 had significantly higher scores on PTSD severity pre- and postdeployment than Classes 2 and 3 (Ps < .001). At postdeployment, Class 1 also had a greater proportion of endorsement of lifetime and past year suicidal ideation than Classes 2 and 3 (Ps < .05) and a greater proportion of lifetime suicide attempts than Class 3 (P < .001). Class 1 also had a greater proportion of endorsement of past-30-days intention to act on suicidal thoughts than Classes 2 and 3 (Ps < .05) and past-30-days specific plan for suicide than Classes 2 and 3 (Ps < .05). The study showed that based only on predeployment data, it is possible to determine which service members might be at highest risk for suicidal ideation and behavior at postdeployment.

Identifying suicidal subtypes and dynamic indicators of increasing and decreasing suicide risk in active duty military personnel: Study protocol.

OBJECTIVES: Several recent studies have demonstrated that posttraumatic stress disorder (PTSD) and insomnia treatments are associated with significant reductions in suicidal ideation (SI) among service members. However, few investigations have evaluated the manner in which suicide risk changes over time among military personnel receiving PTSD or insomnia treatments. This paper describes the study protocol for a project with these aims: (1) explore potential genetic, clinical, and demographic subtypes of suicide risk in a large cohort of deployed service members; (2) explore subtype change in SI as a result of evidence-based psychotherapies for PTSD and insomnia; (3) evaluate the speed of change in suicide risk; and (4) identify predictors of higher- and lower-risk for suicide. METHODS: Active duty military personnel were recruited for four clinical trials (three for PTSD treatment and one for insomnia treatment) and a large prospective epidemiological study of deployed service members, all conducted through the South Texas Research Organizational Network Guiding Studies on Trauma and Resilience (STRONG STAR Consortium). Participants completed similar measures of demographic and clinical characteristics and subsets provided blood samples for genetic testing. The primary measures that we will analyze are the Beck Scale for Suicide Ideation, Beck Depression Inventory, and the PTSD Checklist for DSM-IV. DISCUSSION: Results from this study will offer new insights into the presence of discrete subtypes of suicide risk among active duty personnel, changes in risk over time among those subtypes, and predictors of subtypes. Findings will inform treatment development for military service members at risk for suicide.

Analysis of rare, exonic variation amongst subjects with autism spectrum disorders and population controls.

We report on results from whole-exome sequencing (WES) of 1,039 subjects diagnosed with autism spectrum disorders (ASD) and 870 controls selected from the NIMH repository to be of similar ancestry to cases. The WES data came from two centers using different methods to produce sequence and to call variants from it. Therefore, an initial goal was to ensure the distribution of rare variation was similar for data from different centers. This proved straightforward by filtering called variants by fraction of missing data, read depth, and balance of alternative to reference reads. Results were evaluated using seven samples sequenced at both centers and by results from the association study. Next we addressed how the data and/or results from the centers should be combined. Gene-based analyses of association was an obvious choice, but should statistics for association be combined across centers (meta-analysis) or should data be combined and then analyzed (mega-analysis)? Because of the nature of many gene-based tests, we showed by theory and simulations that mega-analysis has better power than meta-analysis. Finally, before analyzing the data for association, we explored the impact of population structure on rare variant analysis in these data. Like other recent studies, we found evidence that population structure can confound case-control studies by the clustering of rare variants in ancestry space; yet, unlike some recent studies, for these data we found that principal component-based analyses were sufficient to control for ancestry and produce test statistics with appropriate distributions. After using a variety of gene-based tests and both meta- and mega-analysis, we found no new risk genes for ASD in this sample. Our results suggest that standard gene-based tests will require much larger samples of cases and controls before being effective for gene discovery, even for a disorder like ASD.

Genotype-phenotype correlation in hereditary hemorrhagic telangiectasia: mutations and manifestations.

Hereditary hemorrhagic telangiectasia (HHT) is a genetically heterogeneous vascular dysplasia with multiple telangiectases and arteriovenous malformations and it is caused by mutations in endoglin gene (ENG) (HHT1) and activin A receptor type II-like 1 gene (ACVRL1) (HHT2). We evaluated 111 patients with HHT from 34 families by history, examination, screening for vascular malformations, and sequencing of both genes. We found mutations in 26 of the 34 kindreds (76%) analyzed-54% were in ENG and 46% were in ACVRL1. Mutations in ACVRL1 cluster largely in exons 7 and 8, but ENG mutations were widely distributed within that gene. We found that epistaxis had an earlier onset in patients with HHT1 than those with HHT2, but the severity by middle ages was similar. Pulmonary arteriovenous malformations were more frequent and on the average of larger size in HHT1. Hepatic vascular malformations were more common in patients with HHT2. Cerebral arteriovenous malformations were more common in patients with HHT1, but spinal arteriovenous malformations were seen only in patients with HHT2. Truncating mutations in ENG were associated with more affected organs and more severe hemorrhaging than were missense mutations. We conclude that HHT2 has a later onset than HHT1 and the former may disproportionately involve smaller vessels in tissues with more significant vascular remodeling.