Abstract
Epidemiologic and genetic studies suggest common environmental and genetic risk factors for a number of psychiatric disorders, including depression, bipolar disorder, and schizophrenia. Genetic and environmental factors, especially adverse life events, not only have main effects on disease development but also may interact to shape risk and resilience. Such gene by adversity interactions have been described for FKBP5, an endogenous regulator of the stress-neuroendocrine system, conferring risk for a number of psychiatric disorders. In this review, we present a molecular and cellular model of the consequences of FKBP5 by early adversity interactions. We illustrate how altered genetic and epigenetic regulation of FKBP5 may contribute to disease risk by covering evidence from clinical and preclinical studies of FKBP5 dysregulation, known cell-type and tissue-type expression patterns of FKBP5 in humans and animals, and the role of FKBP5 as a stress-responsive molecular hub modulating many cellular pathways. FKBP5 presents the possibility to better understand the molecular and cellular factors contributing to a disease-relevant gene by environment interaction, with implications for the development of biomarkers and interventions for psychiatric disorders.
| Original language | English |
|---|---|
| Pages (from-to) | 821-830 |
| Number of pages | 10 |
| Journal | Biological Psychiatry |
| Volume | 83 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 15 May 2018 |
Bibliographical note
Funding Information:This work was supported by the European Research Council Starting Grant under the Seventh Research Framework Programme (Grant No. 281338 to EBB) and Australian National Health and Medical Research Council Early Career Fellowship (Grant No. #1105445 to NM).
Funding Information:
This review includes data from the Genotype-Tissue Expression Project, which was supported by the Common Fund of the Office of the Director of the National Institutes of Health and by the National Cancer Institute, National Human Genome Research Institute, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, National Institute of Mental Health, and National Institute of Neurological Disorders and Stroke. The data used for the analyses described in this article were obtained from Munich via the Genotype-Tissue Expression Portal on March 19, 2017.
Funding Information:
This work was supported by the European Research Council Starting Grant under the Seventh Research Framework Programme (Grant No. 281338 to EBB) and Australian National Health and Medical Research Council Early Career Fellowship (Grant No. #1105445 to NM).
Publisher Copyright:
© 2018 Society of Biological Psychiatry
Other keywords
- Epigenetics
- FKBP5
- FKBP51
- Gene by environment
- Psychiatric disorders
- Stress