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Further genetic evidence implicates the vasopressin system in childhood‐onset mood disorders
Author(s) -
Dempster Emma L.,
Burcescu Irina,
Wigg Karen,
Kiss Eniko,
Baji Ildiko,
Gadoros Julia,
Tamás Zsuzsanna,
Kapornai Krisztina,
Daróczy Gabriella,
Kennedy James L.,
Vetró Agnes,
Kovacs Maria,
Barr Cathy L.
Publication year - 2009
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2009.06930.x
Subject(s) - vasopressin , mood disorders , mood , psychology , neuroscience , clinical psychology , developmental psychology , medicine , psychiatry , anxiety
Studies in both animals and humans advocate a role for the vasopressin (AVP) system in the aetiology of depressive symptoms. Attention has particularly focused on the role of AVP in the overactivation of the hypothalamic‐pituitary‐adrenal (HPA)‐axis in mood disorders. Elevated AVP plasma levels have been found in mood disorder patients, which are often positively correlated with the severity of symptoms. We recently reported an association between childhood‐onset mood disorders (COMD) and polymorphisms in the receptor responsible for the AVP‐mediated activation of the HPA‐axis ( AVPR1B ). As genetic variation in the vasopressinergic system could provide a mechanism to explain the endocrine alterations observed in mood disorders, we investigated other genes in this system. The gene encoding AVP is the strongest candidate, particularly as genetic variation in this gene in rodents is associated with anxiety‐related behaviours. Six single‐nucleotide polymorphisms (SNPs) were genotyped across the AVP gene in a sample comprised of 586 Hungarian nuclear families ascertained through affected probands with a diagnosis of COMD. In addition, AVP coding and putative regulatory regions were screened for mutations using denaturing high‐performance liquid chromatography. One SNP, 3′ to the AVP, gene reached significance ( P = 0.03), as did the overtransmission of a five‐marker haplotype with a frequency of 22% ( P = 0.0001). The subsequent mutation screen failed to identify any putative functional polymorphisms. The outcome of this study, combined with our previous association between COMD and AVPR1B , implicates genetic variation in vasopressinergic genes in mediating vulnerability to COMD.