Decoding the transcriptomic signatures of psychological trauma in human cortex and amygdala
Year: 2024
Type: preprint
Study design: Observational Study
Abstract: Psychological trauma has profound effects on brain function and precipitates psychiatric disorders in vulnerable individuals, however, the molecular mechanisms linking trauma with psychiatric risk remain incompletely understood. Using RNA-seq data postmortem brain tissue of a cohort of 304 donors (N=136 with trauma exposure), we investigated transcriptional signatures of trauma exposures in two cortical regions (dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex) and two amygdala regions (medial amygdala and basolateral amygdala) associated with stress processing and regulation. We focused on dissecting heterogeneity of traumatic experiences in these transcriptional signatures by investigating exposure to several trauma types (childhood, adulthood, complex, single acute, combat, and interpersonal traumas) and interactions with sex. Overall, amygdala regions were more vulnerable to childhood traumas, whereas cortical regions were more vulnerable to adulthood trauma (regardless of childhood experience). Using cell-type-specific expression imputation, we identified a strong transcriptional response of medial amygdala excitatory neurons to childhood trauma, which coincided with dysregulation observed in a human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons exposed to hydrocortisone. We resolved multiscale coexpression networks for each brain region and identified modules enriched in trauma signatures and whose connectivity was altered with trauma. Trauma-associated coexpression modules provide insight into coordinated functional dysregulation with different traumas and point to potential gene targets for further dissection. Together, these data provide a characterization of the long-lasting human encoding of traumatic experiences in corticolimbic regions of human brain.
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: green
Awards: Predicting the multi-omic impact of psychiatric GWAS associations, Modeling the interaction of physiological and environmental stressors on common variants to psychiatric traits, 3/7 Psychiatric Genomics Consortium: Advancing Discovery and Impact, 1/3 Eating Disorders Genetics Initiative 2 (EDGI2), High-throughput in vivo and in vitro functional and multi-omics screens of neuropsychiatric and neurodevelopmental disorder risk genes, Cross-Population Working Group on Genes and Environment in Major Depression (POP-GEM): Advancing the Understating of Etiology through Diversity, Epigenetic Mechanisms of Chronic Stress Action, Modeling gene x environment interactions in post-traumatic stress disorder.
OpenAlex ID: W4403669962