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The CRF system, stress, depression and anxiety—insights from human genetic studies

Abstract

A concatenation of findings from preclinical and clinical studies support a preeminent function for the corticotropin-releasing factor (CRF) system in mediating the physiological response to external stressors and in the pathophysiology of anxiety and depression. Recently, human genetic studies have provided considerable support to several long-standing hypotheses of mood and anxiety disorders, including the CRF hypothesis. These data, reviewed in this report, are congruent with the hypothesis that this system is of paramount importance in mediating stress-related psychopathology. More specifically, variants in the gene encoding the CRF1 receptor interact with adverse environmental factors to predict risk for stress-related psychiatric disorders. In-depth characterization of these variants will likely be important in furthering our understanding of the long-term consequences of adverse experience.

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Acknowledgements

Support was received from NIH grants MH-42088, MH-69056, MH-58922 and RR-25008. Dr Binder is supported by a Doris Duke Clinical Scientist Development Award.

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Currently, Dr Nemeroff serves on the Scientific Advisory Board for the American Foundation for Suicide Prevention; AstraZeneca; NARSAD, PharmaNeuroboost and CeNeRx. He serves on the Board of Directors of American Foundation for Suicide Prevention; George West Mental Health Foundation; NovaDel Pharma, Mt Cook Pharma, Inc. He owns equity or is stock holder in Corcept; Revaax; NovaDel Pharma; CeNeRx, PharmaNeuroboost, Mt Cook Pharma. He is inventor on the following patents: method and devices for transdermal delivery of lithium (US 6,375,990 B1) and method to estimate serotonin and norepinephrine transporter occupancy after drug treatment using patient or animal serum (provisional filing April, 2001). Currently, Dr Binder receives grant support from NIMH and the Doris Duke charitable foundation.

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Binder, E., Nemeroff, C. The CRF system, stress, depression and anxiety—insights from human genetic studies. Mol Psychiatry 15, 574–588 (2010). https://doi.org/10.1038/mp.2009.141

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Keywords

  • CRF
  • CRH
  • receptor
  • genetic
  • depression
  • anxiety

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