Unknown,Transcriptomics,Genomics,Proteomics

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Investigating the first genomic response to stress – insights into the etiology and pathophysiology of major depression


ABSTRACT: While exposure to adverse life events and subsequent dysregulation of the stress hormone response broadly confer risk for depression, the specific molecular mechanisms mediating this risk are poorly understood. Through pharmacologic activation of the stress hormone response in blood cells we demonstrate that common genetic variants in long-range enhancer elements moderate the immediate transcriptome response to stress, and that these genetic differences are associated with increased risk for depression in the context of early adversity. Using imaging genetics we then link these common risk variants with dysregulated amygdala reactivity, an important trigger of the stress hormone response. The transcripts regulated by these risk variants in peripheral blood were also responsive to stress and stress hormone receptor activation in murine brain. Network modeling approaches suggest that these differences in transcriptional activation may mediate stress-related risk for depression by altering a functional gene network related to proteasome degradation and synaptic plasticity. A Dexamethasone Suppression Test was performed in 160 male subjects. Baseline and stimulated (3 hours after 1.5 mg dexamethasone p.o.) whole blood samples were analyzed using Illumina Human HT-12 v3 arrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Janine Arloth 

PROVIDER: E-GEOD-46743 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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