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Emma L. Dempster, PhD; Irina Burcescu, MSc; Karen Wigg, BSc; Eniko Kiss, MD; Ildiko Baji, MD; Julia Gadoros, MD; Zsuzsanna Tamás, MD; James L. Kennedy, MD, MSc; Ágnes Vetró, MD; Maria Kovacs, PhD; Cathy L. Barr, PhD; for the International Consortium for Childhood-Onset Mood Disorders

Arch Gen Psychiatry. 2007;64(10):1189-1195.

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: ² = 7.81, P = .005; S4: 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 (²₃ = 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.

Author Affiliations: Genetics and Development Division, Toronto Western Research Institute, University Health Network (Drs Dempster and Barr and Mss Burcescu and Wigg), Neurogenetics Section, Centre for Addiction and Mental Health (Dr Kennedy), and Program in Neurosciences and Mental Health, The Hospital for Sick Children (Dr Barr), Toronto, Ontario, Canada; Department of Child and Adolescent Psychiatry, Szeged University, Szeged, Hungary (Drs Kiss and Vetró); Vadaskert Hospital, Budapest, Hungary (Drs Baji, Gadoros, and Tamás); and University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (Dr Kovacs).