As discussion of stress and stress-related disorders rapidly extends beyond the brain, gut microbiota have emerged as a promising contributor to individual differences in the risk of illness, disease course, and treatment response. Here, we employed chronic mild social defeat stress and 16S rRNA gene metagenomic sequencing to investigate the role of microbial composition in mediating anxiety- and depressive-like behavior. In socially defeated animals, we found significant reductions in the overall diversity and relative abundances of numerous bacterial genera, including Akkermansia spp., that positively correlated with behavioral metrics of both anxiety and depression. Functional analyses predicted a reduced frequency of signaling molecule pathways, including G-protein-coupled receptors, in defeated animals. Collectively, our data suggest that shifts in microbial composition may play a role in the pathogenesis of anxiety and depression.

Background: Alcohol use has been reliably associated with smaller subcortical and cortical regional gray matter volumes (GMVs). Whether these associations reflect shared predisposing risk factors and/or causal consequences of alcohol use remains poorly understood.Methods: Data came from 3 neuroimaging samples (total n=2,423), spanning childhood/adolescence to middle age, with prospective or family-based data. First, we identified replicable GMV correlates of alcohol use. Next, we used family-based and longitudinal data to test whether these associations may plausibly reflect a predispositional liability for alcohol use, and/or a causal consequence of alcohol use. Finally, we evaluated whether GWAS-defined genomic risk for alcohol consumption is enriched for genes preferentially expressed in regions identified in our neuroimaging analyses, using heritability and gene-set enrichment, and transcriptome-wide association study (TWAS) approaches.Results: Smaller right dorsolateral prefrontal cortex (DLPFC; i.e., middle and superior frontal gyri) and insula GMVs were associated with increased alcohol use across samples. Family-based and prospective longitudinal data suggest these associations are genetically conferred and that DLPFC GMV prospectively predicts future use and initiation. Genomic risk for alcohol use was enriched in gene-sets preferentially expressed in the DLPFC and associated with differential expression of C16orf93, CWF19L1, and C18orf8 in the DLPFC.Conclusions: These data suggest that smaller DLPFC and insula GMV plausibly represent predispositional risk factors for, as opposed to consequences of, alcohol use. Alcohol use, particularly when heavy, may potentiate these predispositional risk factors. DLPFC and insula .

There is robust evidence that early poverty is associated with poor developmental outcomes, including impaired emotion regulation and depression. However, the specific mechanisms that mediate this risk are less clear. Here we test the hypothesis that one pathway involves hormone mechanisms (testosterone and DHEA) that contribute to disruption of hippocampal brain development, which in turn contributes to perturbed emotion regulation and subsequent risk for depression. To do so, we used data from 167 children participating in the Preschool Depression Study, a longitudinal study that followed children from preschool (ages 3 to 5 y) to late adolescence, and which includes prospective assessments of poverty in preschool, measures of testosterone, DHEA, and hippocampal volume across school age and adolescence, and measures of emotion regulation and depression in adolescence. Using multilevel modeling and linear regression, we found that early poverty predicted shallower increases of testosterone, but not DHEA, across development, which in turn predicted shallower trajectories of hippocampal development. Further, we found that early poverty predicted both impaired emotion regulation and depression. The relationship between early poverty and self-reported depression in adolescence was explained by serial mediation through testosterone to hippocampus to emotion dysregulation. There were no significant interactions with sex. These results provide evidence about a hormonal pathway by which early poverty may contribute to disrupted brain development and risk for mental health problems later in life. Identification of such pathways provide evidence for potential points of intervention that might help mitigate the impact of early adversity on brain development.

On behalf of the STRONG STAR ConsortiumObjective: Using Stein et al.'s (2012) categorization scheme for typing Criterion A events (i.e., Life Threat to Self, Life Threat to Other, Aftermath of Violence, Traumatic Loss, Moral Injury by Self, and Moral Injury by Other) and extending Litz et al.'s (2018) prior work, we investigated the prevalence of trauma types, prevalence of posttraumatic stress disorder within each trauma type, and associations between trauma types and behavioral and mental health outcomes for an epidemiological sample of service members. Method: Criterion A events coded by independent raters (kappas ϭ .85-1.00) were used to determine prevalence rates and to conduct two path models examining all trauma types in relation to mental health outcomes. Results: Consistent with prior research, we found events containing Life Threat to Self (51.1%) and Life Threat to Other (30.8%) to be most prevalent, and a majority of events (62.9%) were coded with one trauma type. Although least prevalent, Aftermath of Violence (12.0%) and Moral Injury by Self (4.8%) were most frequently and strongly associated with worse mental health outcomes. Path models predicted a very small amount of variance in continuous outcomes, thus limiting the interpretation of findings. Conclusion: More epidemiological research is needed to understand the role of trauma type in relation to mental health among nontreatment-seeking service members.

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Adolescents on a trajectory of early alcohol use initiation have higher levels of stress, have increased threat-related amygdala activity, are more likely to consume a full standard alcoholic drink, are more likely to experience early intoxication, and are at a heightened risk for the onset of an alcohol use disorder.

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Background: Adolescence represents a critical developmental period during which the initial onset of depression emerges. Family risk for depression is a salient risk factor for the initial onset of Major Depressive Disorder (MDD). We examined the effects of familial risk, stress, and behavior on the risk of developing first-onset depression.Methods: Adolescents aged 12 to 15 with high (n = 166) or low (n = 159) familial risk for depression were assessed annually for up to five years. Stress was assessed using the Stressful Life Events Schedule and Childhood Trauma Questionnaire. The Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version was administered to the adolescents and their parents to assess lifetime psychiatric conditions and diagnose MDD onset. Survival and path analyses were used in tandem to determine the risk for first-onset depression as well as the contributions of additional direct and indirect pathways to onset.Results: High-risk adolescents were eight times more likely to develop first-onset depression compared with low-risk adolescents. The path analyses revealed that the presence of maternal behavioral disorders and increased recent life stress directly predicted an initial onset of MDD in high-risk adolescents. Limitations:The small samples used in this study limit the generalizability of these findings.