The cerebello-hypothalamic-pituitary-adrenal axis dysregulation hypothesis in depressive disorder

Med Hypotheses. 2012 Dec;79(6):779-83. doi: 10.1016/j.mehy.2012.08.027. Epub 2012 Sep 20.


Depressive disorder can be viewed as an adaptive defense mechanism in response to excessive stress that has gone awry. The hypothalamic-pituitary-adrenal (HPA) axis is an important node in the brain's stress circuit and suggested to play a role in several subtypes of depression. While the hippocampus, amygdala and prefrontal cortex are considered important regions implicated in stress regulation and depressive disorder, the existence of reciprocal monosynaptic cerebello-hypothalamic connections and the presence of dense glucocorticoid binding sites point towards the view that the cerebellum plays a functional role in the regulation of HPA-axis as well. The present hypothesis may further contribute to contemporary neurobiological views on stress regulation and depressive disorder, and may offer a potential biological basis for developing novel neurosomatic treatment protocols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cerebellum / physiopathology*
  • Depressive Disorder / physiopathology*
  • Humans
  • Hypothalamo-Hypophyseal System*
  • Models, Theoretical
  • Pituitary-Adrenal System*