The cortisol awakening response in bipolar illness: a pilot study.
OBJECTIVE
A growing body of data suggests that a significantly enhanced salivary cortisol response to waking may indicate an enduring tendency to abnormal cortisol regulation. Our objective was to apply the response test to a population already known to have long-term hypothalamo-pituitary-adrenocortical (HPA) axis dysregulation. We hypothesized that the free cortisol response to waking, believed to be genetically influenced, would be elevated in a significant percentage of cases, regardless of the afternoon Dexamethasone Suppression Test (DST) value.


METHODS
Using the free cortisol response to waking and the short daytime profile, we tested 18 clinically stable, lithium-responsive subjects from our long-term naturalistic follow-up of monthly DSTs. These tests include salivary testing every 15 minutes during the first hour of waking, followed by samples taken at 3:00 PM and 8:00 PM.


RESULTS
While clinically stable on lithium prophylaxis, patients with bipolar disorder (BD) showed a significantly enhanced salivary cortisol response to waking, compared with control subjects (P < 0.03). Cortisol levels 30 minutes after waking significantly exceeded those in the large normative data provided in the literature (P < 0.001).


CONCLUSIONS
Our observations support the hypothesis that the free cortisol response to waking can reflect relatively enduring HPA dysregulation, even when lithium-responsive BD patients are clinically well and their DSTs are normal. Because the test is easy to administer, the free cortisol response to waking may hold promise as a marker in studies of high-risk families predisposed to, or at risk for, mood disorders.
Deshauer
Dorian
D
Department of Psychiatry, University of Ottawa, Ottawa, Ontario. deshauer1@sympatico.ca
Duffy
Anne
A
Alda
Martin
M
Grof
Eva
E
Albuquerque
Joy
J
Grof
Paul
P
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D003907:Dexamethasone; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology*; D018020:Lithium Compounds / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology*; D012463:Saliva / Q000378:metabolism; D055502:Secondary Prevention; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*
D018020:Lithium Compounds; D003907:Dexamethasone; D006854:Hydrocortisone