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Title: Evidence of an association between the vasopressin V1b receptor gene (AVPR1B) and childhood-onset mood disorders. Author: Dempster EL, Burcescu I, Wigg K, Kiss E, Baji I, Gadoros J, Tamás Z, Kennedy JL, Vetró A, Kovacs M, Barr CL. Journal: Arch Gen Psychiatry; 2007 Oct; 64(10):1189-95. PubMed ID: 17909131. Abstract: CONTEXT: Disturbances in stress hormones have been implicated in mood disorders, in particular in the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Arginine vasopressin (AVP) plays a crucial role in modulating the HPA axis under stress and does so through a G protein-coupled receptor, vasopressin V1b receptor (AVPR1b). OBJECTIVE: To determine if genetic variation in AVPR1B could be contributing to vulnerability to mood disorders. DESIGN: We genotyped single nucleotide polymorphisms (SNPs) across the AVPR1B gene in a family-based sample with childhood-onset mood disorders. Six SNPs were genotyped; 2 were novel nonsynonymous polymorphisms, and the other 4 were constituents of a haplotype that was previously shown to be protective against depression. SETTING: Twenty-three mental health facilities in Hungary. PARTICIPANTS: The sample was composed of 382 Hungarian nuclear families ascertained through affected probands with a diagnosis of childhood-onset mood disorder. MAIN OUTCOME MEASURES: Association with childhood-onset mood disorders was tested using the transmission disequilibrium test, which measures the transmission frequency of alleles, or haplotypes, from parents to affected offspring. RESULTS: Two of the AVPR1B SNPs showed association individually (Lys65Asn: chi(2) = 7.81, P = .005; S4: chi(2) = 4.58, P = .03); of particular interest is Lys65Asn, which causes an amino acid change in an intracellular protein domain. Haplotype analysis demonstrated significant overtransmission of the most frequent haplotype (chi(2)(3) = 22.42, P <.001). Furthermore, stratifying the sample by sex established that the association was predominantly in affected females, which is consistent with previous observations. CONCLUSIONS: We have found evidence to implicate the AVPR1B gene in the etiology of mood disorders, particularly in females. Antagonists of AVPR1b exhibit antidepressant qualities; hence, genetic variation in AVPR1B may have implications in HPA axis dysregulation in mood disorders.[Abstract] [Full Text] [Related] [New Search]