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- W4387496784 abstract "Psychosocial stress is a major precipitating factor in the development of psychiatric disorders, particularly mood and anxiety disorders. The neurobiological consequences of stress have been studied extensively in animal models, however similar molecular analyses in humans have proved challenging. Recent transcriptomic studies of human postmortem brains have focused on case/control status of stress-related disorders such as Post Traumatic Stress Disorder (PTSD) and major depressive disorder (MDD). However, fewer studies have addressed heterogeneity among these disorders. Using RNA-seq data from over 300 postmortem brain donors (dorsolateral prefrontal cortex (DLPFC), dorsal anterior cingulate cortex (dACC), medial amygdala (MeA) and basolateral amygdala (BLA)) with extensive trauma history information, we identified genes differentially expressed in association with trauma. Specifically, we examined gene expression associations with trauma exposure, accumulation of trauma over the lifespan, trauma specific to developmental time periods (ie. childhood trauma) and types of trauma. We found trauma signatures to be distinct from transcriptional signatures of PTSD and MDD. We identified 305 unique genes associated with at least one trauma measure; 102 were associated with 2 or more trauma measures or brain regions. Several genes such as ABCC9, FNDC7 and PTCH2 in the dACC and ACVR1 in the MeA were downregulated with multiple trauma measures. We also compared our transcriptomic signatures of trauma with that in mouse models of stress (chronic social defeat, chronic variable stress, and early life stress). We identified a significant correlation between transcriptional signatures of lifetime trauma accumulation and early life stress in male mice (Spearman rho = 0.254; p < 0.001) in the frontal cortex. Altogether, this study constitutes the first characterization of the gene expression associations with various aspects of trauma in the human postmortem brain. By furthering our understanding of the neurobiological consequences of stress in the brain, we aim to improve care for trauma-exposed individuals and identify interventions to prevent the development of psychiatric disorders." @default.
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- W4387496784 date "2023-10-01" @default.
- W4387496784 modified "2023-10-12" @default.
- W4387496784 title "29. GENE EXPRESSION ASSOCIATIONS WITH TRAUMA IN HUMAN POSTMORTEM BRAIN" @default.
- W4387496784 doi "https://doi.org/10.1016/j.euroneuro.2023.08.139" @default.
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