Hypothalamic-pituitary-adrenal axis and bipolar disorder

Psychiatr Clin North Am. 2005 Jun;28(2):469-80. doi: 10.1016/j.psc.2005.01.005.


There is robust evidence demonstrating abnormalities of the HPA axis in bipolar disorder. Hypercortisolism may be central to the pathogenesis of depressive symptoms and cognitive deficits, which may in turn result from neurocytotoxic effects of raised cortisol levels. Manic episodes may be preceded by increased ACTH and cortisol levels, leading to cognitive problems and functional impairments. Identification and effective treatment of mood and cognitive symptoms of mood disorders are clinical goals, but currently available treatments may fall short of this ideal. Manipulation of the HPA axis has been shown to have therapeutic effects in preclinical and clinical studies, and recent data suggest that direct antagonism of GRs maybe a future therapeutic strategy in the treatment of mood disorders.

Publication types

  • Review

MeSH terms

  • Antimanic Agents / therapeutic use
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / physiopathology*
  • Brain / drug effects
  • Brain / physiopathology
  • Feedback / physiology
  • Glucocorticoids / blood
  • Humans
  • Hydrocortisone / blood
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Lithium Carbonate / therapeutic use
  • Nerve Net / drug effects
  • Nerve Net / physiopathology
  • Neurons / drug effects
  • Neurons / physiology
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / physiopathology*
  • Receptors, Glucocorticoid / antagonists & inhibitors
  • Receptors, Glucocorticoid / physiology
  • Treatment Outcome


  • Antimanic Agents
  • Glucocorticoids
  • Receptors, Glucocorticoid
  • Lithium Carbonate
  • Hydrocortisone