Cortisol and depression: three questions for psychiatry

Psychol Med. 2013 Mar;43(3):449-69. doi: 10.1017/S0033291712000955. Epub 2012 May 8.


Background: Cortisol plays a multifaceted role in major depression disorder (MDD). Diurnal rhythms are disturbed, there is increased resistance to the feedback action of glucocorticoids, excess cortisol may induce MDD, basal levels may be higher and the post-awakening cortisol surge accentuated in those at risk for MDD. Does this suggest new avenues for studying MDD or its clinical management?

Method: The relevant literature was reviewed.

Results: Cortisol contributes to genetic variants for the risk for MDD and the way that environmental events amplify risk. The corticoids' influence begins prenatally, but continues into adulthood. The impact of cortisol at each phase depends not only on its interaction with other factors, such as psychological traits and genetic variants, but also on events that have, or have not, occurred previously.

Conclusions: This review suggests that the time is now right for serious consideration of the role of cortisol in a clinical context. Estimates of cortisol levels and the shape of the diurnal rhythm might well guide the understanding of subtypes of MDD and yield additional indicators for optimal treatment. Patients with disturbed cortisol rhythms might benefit from restitution of those rhythms; they may be distinct from those with more generally elevated levels, who might benefit from cortisol blockade. Higher levels of cortisol are a risk for subsequent depression. Should manipulation of cortisol or its receptors be considered as a preventive measure for some of those at very high risk of future MDD, or to reduce other cortisol-related consequences such as long-term cognitive decline?

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Brain / metabolism*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Brain-Derived Neurotrophic Factor / physiology
  • Chronobiology Disorders / metabolism
  • Chronobiology Disorders / physiopathology
  • Circadian Rhythm / physiology*
  • Corticotropin-Releasing Hormone / metabolism
  • Corticotropin-Releasing Hormone / physiology
  • Dehydroepiandrosterone / metabolism
  • Dehydroepiandrosterone / physiology
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / genetics
  • Depressive Disorder, Major / metabolism*
  • Disease Susceptibility
  • Gene Expression
  • Gene-Environment Interaction
  • Hormone Antagonists / therapeutic use
  • Humans
  • Hydrocortisone* / metabolism
  • Hydrocortisone* / physiology
  • Hypothalamo-Hypophyseal System / physiopathology
  • Mifepristone / therapeutic use
  • Neurogenesis / physiology
  • Pituitary-Adrenal System / physiopathology
  • Psychiatry*
  • Receptors, Glucocorticoid / antagonists & inhibitors
  • Risk Factors
  • Sex Characteristics
  • Stress, Psychological / metabolism*
  • Temperament
  • Treatment Outcome


  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Hormone Antagonists
  • Receptors, Glucocorticoid
  • hydrocortisone receptor
  • Mifepristone
  • Dehydroepiandrosterone
  • Corticotropin-Releasing Hormone
  • Hydrocortisone