Hypothalamic-pituitary-adrenocortical axis dysregulation in patients with major depression is influenced by the insertion/deletion polymorphism in the angiotensin I-converting enzyme gene.
The Dex/CRH test is one of the most reliable neuroendocrine function tests for hypothalamic-pituitary-adrenocortical (HPA) system dysregulation in depression. Persistent overdrive of HPA system activity after successful antidepressant treatment predicts an enhanced risk for relapse of a depressive episode. As the renin-angiotensin system has been shown to play a role in HPA system activity, we investigated the impact of the angiotensin converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism, which determines ACE plasma concentrations, on HPA system dysregulation. We performed repeated combined Dex/CRH tests in 115 patients suffering from major depression. Dex/CRH test results were related to the I/D polymorphism within the ACE gene, which was assessed by PCR. Genotype frequencies were comparable to those in the general population (I/I 16.8%, I/D 59.3%, D/D 23.9%). D/D genotypes showed a higher cortisol stimulation during the first Dex/CRH test after admission than homozygous I-allele carriers (repeated measurement ANOVA: P=0.034). Cortisol area under the curve values were highest in those with the D/D genotype (mean+/-SEM [nmol/l*75 min]: 12700+/-2220), intermediate in those with the I/D genotype (9570+/-1000), and lowest in those with the I/I genotype (5160+/-1000; ANOVA: P=0.04). After successful antidepressive treatment and attenuation of HPA system overdrive these differences were no more detectable. The HPA axis stimulating properties of higher ACE and consecutively higher AT-II and/or lower substance P concentrations may be crucial factors for the HPA system hyperactivity during major depressive episodes.
Baghai
Thomas C
TC
Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University of Munich, Nussbaumstrasse 7, D-80336, Munich, Germany. baghai@psy.med.uni-muenchen.de
Schule
Cornelius
C
Zwanzger
Peter
P
Minov
Christo
C
Zill
Peter
P
Ella
Robin
R
Eser
Daniela
D
Oezer
Sebnem
S
Bondy
Brigitta
B
Rupprecht
Rainer
R
D000302:Adrenal Cortex / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use; D003346:Corticotropin-Releasing Hormone; D004251:DNA Transposable Elements; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D003907:Dexamethasone; D005260:Female; D017353:Gene Deletion; D005938:Glucocorticoids; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011110:Polymorphism, Genetic
D000928:Antidepressive Agents; D004251:DNA Transposable Elements; D005938:Glucocorticoids; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D007703:Peptidyl-Dipeptidase A; D006854:Hydrocortisone