Major depression in late life is associated with both hypo- and hypercortisolemia

Biol Psychiatry. 2007 Sep 1;62(5):479-86. doi: 10.1016/j.biopsych.2006.11.033. Epub 2007 May 3.


Background: In younger adults, depression has been associated with hypercortisolemia. In older depressed patients, however, both low and high cortisol levels have been reported. We examined the possibility of a U-shaped association between depression and cortisol in older people, suggesting both hypo- and hyperactivity of the hypothalamic-pituitary-adrenal axis. We also examined whether this might represent different depression subtypes.

Methods: This population-based study included 1185 subjects aged 65 and older. Depression was measured at both diagnostic (major depression) and symptomatic (subthreshold depression) levels of caseness. Plasma concentrations of cortisol (CORT) and corticosteroid binding globulin (CBG) were determined. From these (CORT/CBG), a free cortisol index (FCI) was computed.

Results: The association between cortisol and major depression was U-shaped (B CORT = -9.50 [SE 3.85] p = .014; B CORT(2) = .008 [SE .003] p = .021). Hypocortisolemic depression (lower cortisol tertile) was associated with female sex, joint diseases, and smoking. Hypercortisolemic (upper cortisol tertile) depression was associated with older age, male sex, cardiovascular diseases, nonsteroidal antiinflammatory use, and (borderline significant) cognitive impairment.

Conclusions: In older people, the association between cortisol and major depression is U-shaped. Hypo- and hypercortisolemic depression may represent different depression subtypes, requiring different clinical management.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Insufficiency / complications*
  • Adrenal Insufficiency / metabolism
  • Adrenocortical Hyperfunction / complications*
  • Adrenocortical Hyperfunction / metabolism
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Community Health Planning
  • Depressive Disorder, Major / classification
  • Depressive Disorder, Major / complications*
  • Depressive Disorder, Major / metabolism*
  • Female
  • Geriatric Assessment*
  • Humans
  • Hydrocortisone / blood*
  • Male
  • Psychiatric Status Rating Scales
  • Transcortin / metabolism


  • Transcortin
  • Hydrocortisone