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 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.