title: The angiotensin I converting enzyme insertion/deletion polymorphism influences therapeutic outcome in major depressed women, but not in men.
abstract: Angiotensin converting enzyme (ACE) is expressed in the central nervous system (CNS), where its primary function comprises degradation of neuropeptides including substance P (SP). Because of the possible antidepressant effects of SP antagonists, the influence of SP on both pathophysiology and mitigation of depression has been hypothesized. It was shown that ACE plasma concentration is determined by an insertion/deletion (I/D) polymorphism represented by the presence or absence of a 287 bp DNA fragment within the ACE gene. Because the D allele was associated with higher ACE levels this may have a positive impact on the therapeutic efficacy of antidepressant treatment. Thus, variations in CNS expression of ACE might influence the response to various antidepressant therapies. We could show a divergent clinical outcome in relation to different genotypes in 313 depressed patients who were treated with various antidepressants. A lower HAM-D17 score after 4 weeks of treatment in D/D and I/D in comparison to I/I genotypes was detected; the duration of hospitalization was shorter in D allele carriers. The D allele seems to be a predictor for a faster onset of different antidepressant therapies. The patients' gender influences these outcome effects significantly. After subdivision of the patients according to their gender only female patients contributed significantly to the genotype dependent therapeutic outcome. Our investigation gives the first hint that the speed of onset of antidepressant therapies may be dependent on both variants of the ACE genes and the gender of the patients.
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University of Munich, Nussbaumstrasse 7, D-80336 Munich, Germany. baghai@med.uni-muenchen.de
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Baghai
authors.forename: Cornelius
authors.initials: C
authors.lastname: Schule
authors.forename: Peter
authors.initials: P
authors.lastname: Zill
authors.forename: Tobias
authors.initials: T
authors.lastname: Deiml
authors.forename: Daniela
authors.initials: D
authors.lastname: Eser
authors.forename: Peter
authors.initials: P
authors.lastname: Zwanzger
authors.forename: Robin
authors.initials: R
authors.lastname: Ella
authors.forename: Rainer
authors.initials: R
authors.lastname: Rupprecht
authors.forename: Brigitta
authors.initials: B
authors.lastname: Bondy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000627:therapeutic use; D016009:Chi-Square Distribution; D002869:Chromosome Aberrations; D003865:Major Depressive Disorder / Q000235:genetics* / Q000628:therapy; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012727:Sex Characteristics; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D007703:Peptidyl-Dipeptidase A