The hypothalamic-pituitary-cortisol system in depression

The hypothalamic-pituitary-cortisol hypothesis of depression postulates that abnormalities in the cortisol response to stress may underlie depression. The blue arrows show that in response to stress, which is perceived by the brain cortex and the amygdala and transmitted to the hypothalamus, corticotropin-releasing hormone (CRH) is released, inducing the anterior pituitary gland to secrete corticotropin into the bloodstream. Corticotropin stimulates the adrenal cortexes to secrete the glucocorticoid hormone cortisol. The red arrows show that cortisol, in turn, induces feedback inhibition in the hypothalamus and the pituitary, suppressing the production of CRH and corticotropin, respectively. Findings in patients with depression that support the hypothalamic-pituitary-cortisol hypothesis include the following: cortisol levels may be elevated, suppression of cortisol by exogenous corticosteroids may be reduced, the size of the anterior pituitary and adrenal cortex is increased, and CRH levels in the cerebrospinal fluid and CRH expression in the limbic brain regions are increased. Hippocampal size and the numbers of neurons and glia are decreased, possibly reflecting reduced neurogenesis due to elevated cortisol levels or due to reduced brain-derived neurotrophic factor.