title: Beta-1-adrenergic receptor gene in major depression: influence on antidepressant treatment response.
abstract: Noradrenergic dysfunction has been implicated in the development of affective disorders. beta-adrenergic receptors (betaARs) mediate the response to norephinephrine, are coupled to the cAMP signaling cascade, supposed to be altered in their density and/or sensitivity in depression, and down regulated in several brain regions after long term treatment with different but not all antidepressants. A recently identified functional polymorphism in the beta(1)-adrenergic receptor (G1165C) leading to the amino acid variation Gly389Arg was associated with an enhanced coupling to the stimulatory G(s)-protein and increased adenylyl cyclase activation, disturbances which are often observed in affective disorders. Therefore, we investigated whether this beta(1)AR polymorphism is associated with major depression or with the response to antidepressant treatment in a sample of 259 patients compared to 206 healthy controls. Although we could not detect an association between the beta(1)AR polymorphism and major depression we found a tendency for a relation between CC homozygosity and a better and even faster response to antidepressant treatment in those patients, which were treated with antidepressants affecting directly or indirectly the beta(1)AR system (tricyclic antidepressants, noradrenergic and serotonergic specific agents, selective noradrenaline reuptake inhibitors) determined by the HAMD and CGI score (P = 0.05). However, after correction for multiple testing (Bonferroni) these results did not remain significant. Nevertheless, these findings suggest that the presence of the C allele might be an indicator for antidepressant treatment response.
authors.affiliation: Psychiatric Hospital of the Ludwig-Maximilians-University, Munich, Germany. Peter.Zill@psy.med.uni-muenchen.de
authors.forename: Peter
authors.initials: P
authors.lastname: Zill
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Baghai
authors.forename: Rolf
authors.initials: R
authors.lastname: Engel
authors.forename: Peter
authors.initials: P
authors.lastname: Zwanzger
authors.forename: Cornelius
authors.initials: C
authors.lastname: Schüle
authors.forename: Christo
authors.initials: C
authors.lastname: Minov
authors.forename: Stefanie
authors.initials: S
authors.lastname: Behrens
authors.forename: Ronald
authors.initials: R
authors.lastname: Bottlender
authors.forename: Markus
authors.initials: M
authors.lastname: Jäger
authors.forename: Rainer
authors.initials: R
authors.lastname: Rupprecht
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Möller
authors.forename: Manfred
authors.initials: M
authors.lastname: Ackenheil
authors.forename: Brigitta
authors.initials: B
authors.lastname: Bondy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy* / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*
chemical_list: D000928:Antidepressive Agents; D018342:Receptors, Adrenergic, beta-1; D001569:Benzodiazepines