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Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders

Arloth, J and Major Depressive Disorder Working Group, Psychiatric Genomics Consortium and Jones, Lisa and Binder, E (2015) Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders. Neuron, 86 (5). pp. 1189-1202. ISSN 0896-6273

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Abstract

Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain.

Item Type: Article
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Citation for this article:-
Arloth, J., Bogdan, R., Weber, P., Frishman, G., Menke, A., Wagner, K.V., Balsevich, G., Schmidt, M.V., Karbalai, N., Czamara, D. and Altmann, A., 2015. Genetic differences in the immediate transcriptome response to stress predict risk-related brain function and psychiatric disorders. Neuron, 86(5), pp.1189-1202.

Uncontrolled Keywords: genetics, transcriptome, stress, brain function, psychiatric disorders
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Academic Departments > Institute of Health and Society
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Copyright Info: Open Access journal article, Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)
Depositing User: Lisa Jones
Date Deposited: 07 Nov 2016 08:43
Last Modified: 07 Nov 2016 08:43
URI: https://eprints.worc.ac.uk/id/eprint/5045

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