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

Abstract

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.