Circadian regulation of cortisol after hippocampal damage in humans.
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.
Buchanan
Tony W
TW
Department of Neurology, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA. tony-buchanan@uiowa.edu
Kern
Simone
S
Allen
John S
JS
Tranel
Daniel
D
Kirschbaum
Clemens
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001925:Brain Damage, Chronic / Q000378:metabolism*; D017028:Caregivers; D016022:Case-Control Studies; D002940:Circadian Rhythm / Q000502:physiology*; D003710:Demography; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006624:Hippocampus / Q000293:injuries / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012463:Saliva / Q000378:metabolism; D013997:Time Factors
D006854:Hydrocortisone