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


METHODS
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.


METHODS
Twenty-three mental health facilities in Hungary.


METHODS
The sample was composed of 382 Hungarian nuclear families ascertained through affected probands with a diagnosis of childhood-onset mood disorder.


METHODS
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.
Dempster
Emma L
EL
Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario, Canada.
Burcescu
Irina
I
Wigg
Karen
K
Kiss
Eniko
E
Baji
Ildiko
I
Gadoros
Julia
J
Tamás
Zsuzsanna
Z
Kennedy
James L
JL
Vetró
Agnes
A
Kovacs
Maria
M
Barr
Cathy L
CL
D017668:Age of Onset; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D018562:Disease Transmission, Infectious; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D015810:Linkage Disequilibrium / Q000235:genetics; D019964:Mood Disorders / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D009679:Nuclear Family; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D017483:Receptors, Vasopressin / Q000235:genetics*; D012737:Sex Factors
D005819:Genetic Markers; D017483:Receptors, Vasopressin