Circadian regulation of cortisol after hippocampal damage in humans

Biol Psychiatry. 2004 Nov 1;56(9):651-6. doi: 10.1016/j.biopsych.2004.08.014.


Background: There is substantial evidence that the hippocampus (HC) regulates the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis. Damage to the HC in animals produces a transient alteration in diurnal and stress-related HPA activity. This study was designed to examine the effects of HC damage on basal cortisol secretion in humans.

Methods: Salivary cortisol was measured in 22 patients with HC damage (12 with bilateral damage and 10 with unilateral damage), 7 brain-damaged comparison participants, 10 healthy, age-matched comparison participants, and 6 of the patients' caregivers. Salivary cortisol samples were taken immediately after awakening, 30 min after awakening, at 8:00 am, 11:00 am, 3:00 pm, 6:00 pm, and at bedtime on a single day. Brain-injured patients underwent a structural magnetic resonance imaging scan to examine quantitative volumes of the HC.

Results: Both bilateral and unilateral HC damage abolished the cortisol response to awakening documented in the comparison groups. Caregivers of bilateral HC patients showed a reduced response to awakening. The remainder of the circadian pattern was not affected in the HC patients; all groups showed a significant diurnal variation. There was no association between HC volume and cortisol secretion.

Conclusions: Hippocampal damage in humans abolishes the cortisol response to awakening, whereas the remainder of the diurnal cycle is unaffected in these patients. These data suggest a unique role of the HC in the control of basal cortisol secretion.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Brain Damage, Chronic / metabolism*
  • Caregivers
  • Case-Control Studies
  • Circadian Rhythm / physiology*
  • Demography
  • Female
  • Functional Laterality / physiology
  • Hippocampus / injuries
  • Hippocampus / metabolism*
  • Humans
  • Hydrocortisone / pharmacokinetics*
  • Male
  • Middle Aged
  • Reproducibility of Results
  • Saliva / metabolism
  • Time Factors


  • Hydrocortisone