HPA-axis regulation at in-patient admission is associated with antidepressant therapy outcome in male but not in female depressed patients.
A concatenation of data implicates a hyperactivity of the hypothalamus pituitary adrenal (HPA)-axis in the pathogenesis of depression and its normalization as a necessary predecessor of clinical response to antidepressant drugs. In addition, regulation of the HPA-axis has been shown to be dependent on sex hormones. We therefore investigated gender differences in HPA-axis regulation in depression and its normalization during remission of clinical symptoms. We used the combined dexamethasone suppression/CRH stimulation (Dex-CRH) test to evaluate the degree of HPA-axis dysregulation in 194 in-patients with unipolar depression from the Munich Antidepressant Response Signature (MARS) study at both admission and discharge. The Hamilton Depression (HAM-D) Rating Scale was used to monitor clinical response to antidepressant treatment. For both genders, we observed a normalization of HPA-axis dysregulation in remitters but not in non-remitters, both after 5 weeks of treatment and at discharge. The pattern of HPA-axis normalization with remission of depressive symptoms, however, showed gender-specific differences. In male patients, remission after 5 weeks of in-patient treatment was associated with a significantly higher cortisol response in the Dex-CRH test at admission. In female patients, 5-week remitters and non-remitters had a comparable cortisol response at admission. Cortisol response at admission was not correlated with gonadal steroid levels at this time point and the results were similar for pre-menopausal women vs. post-menopausal women. Gender-associated biological characteristics, likely independent of circulating gonadal steroids, thus seem to influence HPA-axis regulation in depression. In male patients, a single measure of HPA-axis dysregulation at admission may serve as a predictor of response to antidepressant treatment in addition to the previously reported repeated measure of the Dex-CRH test.
Binder
E B
EB
Max-Planck Institute of Psychiatry, Kraepelinstrasse 2-10, D80804 Munich, Germany. binder@mpipsykl.mpg.de
Künzel
H E
HE
Nickel
T
T
Kern
N
N
Pfennig
A
A
Majer
M
M
Uhr
M
M
Ising
M
M
Holsboer
F
F
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D012727:Sex Characteristics; D016896:Treatment Outcome
D000928:Antidepressive Agents; D012739:Gonadal Steroid Hormones; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone