Evidence of an association between the vasopressin V1b receptor gene (AVPR1B) and childhood-onset mood disorders

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 childhoodonset 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(3)(2)= 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.