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

Mol Psychiatry. 2010 Jun;15(6):574-88. doi: 10.1038/mp.2009.141. Epub 2009 Dec 15.


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 CRF(1) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anxiety Disorders / genetics*
  • Corticotropin-Releasing Hormone / genetics*
  • Depression / genetics*
  • Genetic Association Studies
  • Genetic Variation
  • Humans
  • Models, Biological
  • Receptors, Corticotropin-Releasing Hormone / genetics*
  • Signal Transduction / genetics
  • Stress, Psychological / genetics*


  • Receptors, Corticotropin-Releasing Hormone
  • CRF receptor type 1
  • Corticotropin-Releasing Hormone