Cortisol circadian rhythm alterations in psychotic major depression.
BACKGROUND
Increased hypothalamic-pituitary-adrenal axis activity is well described in psychotic depression with an emphasis on 24-hour, urinary free cortisol levels or dexamethasone suppression tests. There are limited data on cortisol levels during specific times of the day.


METHODS
Patients with depression with (PMD) and without (NPMD) psychosis and healthy control subjects were studied using rating scales of depression and psychosis and measures of HPA activity, including overnight cortisol and adrenocorticotropin levels. We used analysis of variance to determine group differences and regression analyses to assess contributions of specific measures to cortisol levels.


RESULTS
PMDs had higher cortisol during the evening hours than did NPMDs or control subjects, who did not differ from one another. Regression analyses suggest that depression and the combination of depressive and psychotic symptoms were important contributors to variance in evening cortisol.


CONCLUSIONS
PMD is associated with increased cortisol levels during the quiescent hours. Enhanced cortisol activity, particularly a higher nadir, was related to depression severity and the interaction of depressive and psychotic symptoms. This increase suggests a defect in the action of the circadian timing system and HPA axis, creating a hormonal milieu similarly seen in early Cushing's syndrome and potentially an (im)balance of mineralocorticoid and glucocorticoid receptor activity.
Keller
Jennifer
J
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305-5723, USA. jkeller@stanford.edu
Flores
Benjamin
B
Gomez
Rowena G
RG
Solvason
H Brent
HB
Kenna
Heather
H
Williams
Gordon H
GH
Schatzberg
Alan F
AF
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000704:Analysis of Variance; D021081:Chronobiology Disorders / Q000097:blood* / Q000150:complications / Q000523:psychology; D003865:Major Depressive Disorder / Q000097:blood* / Q000150:complications / Q000523:psychology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000097:blood* / Q000150:complications / Q000523:psychology; D012016:Reference Values; D012720:Severity of Illness Index; D013997:Time Factors
D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone