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

Emma L. Dempster, Irina Burcescu, Karen Wigg, Eniko Kiss, Ildiko Baji, Julia Gadoros, Zsuzsanna Tamás, James L. Kennedy, Ágnes Vetró, Maria Kovacs, Cathy L. Barr

Research output: Article

63 Citations (Scopus)

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: χ2=7.81, P=.005; S4: χ2=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 (χ3 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.

Original languageEnglish
Pages (from-to)1189-1195
Number of pages7
JournalArchives of General Psychiatry
Volume64
Issue number10
DOIs
Publication statusPublished - okt. 1 2007

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health

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