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

Publication ,  Journal Article
Arloth, J; Bogdan, R; Weber, P; Frishman, G; Menke, A; Wagner, KV; Balsevich, G; Schmidt, MV; Karbalai, N; Czamara, D; Altmann, A; Trümbach, D ...
Published in: Neuron
June 2015

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.

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Published In

Neuron

DOI

EISSN

1097-4199

ISSN

0896-6273

Publication Date

June 2015

Volume

86

Issue

5

Start / End Page

1189 / 1202

Related Subject Headings

  • Transcriptome
  • Stress, Psychological
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Neurology & Neurosurgery
  • Mice, Inbred C57BL
  • Mice
  • Mental Disorders
  • Male
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Arloth, J., Bogdan, R., Weber, P., Frishman, G., Menke, A., Wagner, K. V., … Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium PGC, . (2015). Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders. Neuron, 86(5), 1189–1202. https://doi.org/10.1016/j.neuron.2015.05.034
Arloth, Janine, Ryan Bogdan, Peter Weber, Goar Frishman, Andreas Menke, Klaus V. Wagner, Georgia Balsevich, et al. “Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders.Neuron 86, no. 5 (June 2015): 1189–1202. https://doi.org/10.1016/j.neuron.2015.05.034.
Arloth J, Bogdan R, Weber P, Frishman G, Menke A, Wagner KV, et al. Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders. Neuron. 2015 Jun;86(5):1189–202.
Arloth, Janine, et al. “Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders.Neuron, vol. 86, no. 5, June 2015, pp. 1189–202. Epmc, doi:10.1016/j.neuron.2015.05.034.
Arloth J, Bogdan R, Weber P, Frishman G, Menke A, Wagner KV, Balsevich G, Schmidt MV, Karbalai N, Czamara D, Altmann A, Trümbach D, Wurst W, Mehta D, Uhr M, Klengel T, Erhardt A, Carey CE, Conley ED, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (PGC), Ruepp A, Müller-Myhsok B, Hariri AR, Binder EB, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium PGC. Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders. Neuron. 2015 Jun;86(5):1189–1202.
Journal cover image

Published In

Neuron

DOI

EISSN

1097-4199

ISSN

0896-6273

Publication Date

June 2015

Volume

86

Issue

5

Start / End Page

1189 / 1202

Related Subject Headings

  • Transcriptome
  • Stress, Psychological
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Neurology & Neurosurgery
  • Mice, Inbred C57BL
  • Mice
  • Mental Disorders
  • Male
  • Humans