Arloth, J, Major Depressive Disorder Working Group of the, Psychiatric Genomics Consortium, Jones, Lisa ORCID: https://orcid.org/0000-0002-5122-8334 and Binder, E.B. (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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Additional Information: | The full-text can be accessed via the Official URL. |
Uncontrolled Discrete 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: | College of Health, Life and Environmental Sciences > School of Allied Health and Community |
Related URLs: | |
Copyright Info: | Open Access journal article |
Depositing User: | Lisa Jones |
Date Deposited: | 07 Nov 2016 08:43 |
Last Modified: | 17 Jun 2020 17:14 |
URI: | https://eprints.worc.ac.uk/id/eprint/5045 |
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