Stress dynamically regulates co-expression networks of glucocorticoid receptor-dependent MDD and SCZ risk genes View Full Text


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Article Info

DATE

2019-12

AUTHORS

Christoph A. Zimmermann, Janine Arloth, Sara Santarelli, Anne Löschner, Peter Weber, Mathias V. Schmidt, Dietmar Spengler, Elisabeth B. Binder

ABSTRACT

Early-life adversity is an important risk factor for major depressive disorder (MDD) and schizophrenia (SCZ) that interacts with genetic factors to confer disease risk through mechanisms that are still insufficiently understood. One downstream effect of early-life adversity is the activation of glucocorticoid receptor (GR)-dependent gene networks that drive acute and long-term adaptive behavioral and cellular responses to stress. We have previously shown that genetic variants that moderate GR-induced gene transcription (GR-response eSNPs) are significantly enriched among risk variants from genome-wide association studies (GWASs) for MDD and SCZ. Here, we show that the 63 transcripts regulated by these disease-associated functional genetic variants form a tight glucocorticoid-responsive co-expression network (termed GCN). We hypothesized that changes in the correlation structure of this GCN may contribute to early-life adversity-associated disease risk. Therefore, we analyzed the effects of different qualities of social support and stress throughout life on GCN formation across distinct brain regions using a translational mouse model. We observed that different qualities of social experience substantially affect GCN structure in a highly brain region-specific manner. GCN changes were predominantly found in two functionally interconnected regions, the ventral hippocampus and the hypothalamus, two brain regions previously shown to be of relevance for the stress response, as well as psychiatric disorders. Overall, our results support the hypothesis that a subset of genetic variants may contribute to risk for MDD and SCZ by altering circuit-level effects of early and adult social experiences on GCN formation and structure. More... »

PAGES

41

References to SciGraph publications

  • 2010-11-11. The environment and schizophrenia in NATURE
  • 2015-10. Mechanisms of stress in the brain in NATURE NEUROSCIENCE
  • 2010. Systems Biology Approaches and Tools for Analysis of Interactomes and Multi-target Drugs in SYSTEMS BIOLOGY IN DRUG DISCOVERY AND DEVELOPMENT
  • 2013-12. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool in BMC BIOINFORMATICS
  • 2010-11-11. From maps to mechanisms through neuroimaging of schizophrenia in NATURE
  • 2016-09. Consistently altered expression of gene sets in postmortem brains of individuals with major psychiatric disorders in TRANSLATIONAL PSYCHIATRY
  • 2012-05. Social influences on neuroplasticity: stress and interventions to promote well-being in NATURE NEUROSCIENCE
  • 2015-11-12. Schizophrenia in NATURE REVIEWS DISEASE PRIMERS
  • 2014-12. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 in GENOME BIOLOGY
  • 2011-03. Chromatin accessibility pre-determines glucocorticoid receptor binding patterns in NATURE GENETICS
  • 2016-01. The role of inflammation in depression: from evolutionary imperative to modern treatment target in NATURE REVIEWS IMMUNOLOGY
  • 2017-10-26. Genetic insights into the neurodevelopmental origins of schizophrenia in NATURE REVIEWS NEUROSCIENCE
  • 2015-02. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways in NATURE NEUROSCIENCE
  • 2008-11. Ubiquitin, the proteasome and protein degradation in neuronal function and dysfunction in NATURE REVIEWS NEUROSCIENCE
  • 2015. Mechanisms of Glucocorticoid-Regulated Gene Transcription in GLUCOCORTICOID SIGNALING
  • 2015-04. The role of regulatory variation in complex traits and disease in NATURE REVIEWS GENETICS
  • 2007-09. Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic in NATURE NEUROSCIENCE
  • 2017-09. Sex-specific transcriptional signatures in human depression in NATURE MEDICINE
  • 2009-06. Effects of stress throughout the lifespan on the brain, behaviour and cognition in NATURE REVIEWS NEUROSCIENCE
  • 2015-10. Reduced protein synthesis in schizophrenia patient-derived olfactory cells in TRANSLATIONAL PSYCHIATRY
  • 2015-10. Increased abundance of translation machinery in stem cell–derived neural progenitor cells from four schizophrenia patients in TRANSLATIONAL PSYCHIATRY
  • 2011-10. Spatio-temporal transcriptome of the human brain in NATURE
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    URI

    http://scigraph.springernature.com/pub.10.1038/s41398-019-0373-1

    DOI

    http://dx.doi.org/10.1038/s41398-019-0373-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111747609

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30696808


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