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Contribution of oxytocin receptor polymorphisms to amygdala activation in schizophrenia spectrum disorders.

ABSTRACT: BACKGROUND:Oxytocin has been proposed to mediate amygdala dysfunction associated with altered emotion processing in schizophrenia, but the contribution of oxytocin pathway genes is yet to be investigated. AIMS:To identify potential different contributions of three oxytocin receptor polymorphisms (rs53576, rs237902 and rs2254298) between patients with schizophrenia spectrum disorders (SCZ), affective spectrum disorders (AD) and healthy controls (HC). METHOD:In a total of 346 participants (104 with SCZ, 100 with AD, and 142 HC) underwent genotyping and functional magnetic resonance imaging (fMRI) during an emotional faces matching paradigm. Genetic association analyses were performed to test the possible effects on task-induced BOLD amygdala response to fearful/angry faces. RESULTS:In participants with SCZ, the rs237902 G allele was associated with low amygdala activation (left hemisphere: b=-4.99, Bonferroni corrected P=0.04) and interaction analyses showed that this association was disorder specific (left hemisphere: Bonferroni corrected P=0.003; right hemisphere: Bonferroni corrected P=0.03). There were no associations between oxytocin polymorphisms and amygdala activation in the total sample, among AD patients or HC. CONCLUSIONS:Rs237902 was associated with amygdala activation in response to fearful/angry faces only in patients with SCZ. Our findings indicate that the endogenous oxytocin system could serve as a contributing factor in biological underpinnings of emotion processing and that this contribution is disorder specific. DECLARATION OF INTEREST:O.A.A. received speaker's honoraria from GSK, Otsuka, Lundbeck. COPYRIGHT AND USAGE:© The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

SUBMITTER: Haram M

PROVIDER: S-EPMC5099986 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Contribution of oxytocin receptor polymorphisms to amygdala activation in schizophrenia spectrum disorders.

Haram Marit M Bettella Francesco F Brandt Christine Lycke CL Quintana Daniel S DS Nerhus Mari M Bjella Thomas T Djurovic Srdjan S Westlye Lars T LT Andreassen Ole A OA Melle Ingrid I Tesli Martin M

BJPsych open 20161103 6

<h4>Background</h4>Oxytocin has been proposed to mediate amygdala dysfunction associated with altered emotion processing in schizophrenia, but the contribution of oxytocin pathway genes is yet to be investigated.<h4>Aims</h4>To identify potential different contributions of three oxytocin receptor polymorphisms (rs53576, rs237902 and rs2254298) between patients with schizophrenia spectrum disorders (SCZ), affective spectrum disorders (AD) and healthy controls (HC).<h4>Method</h4>In a total of 346 ...[more]

PMID: 27847593

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Project description:Background and aimsOxytocin, a nine amino acid peptide synthesised in the hypothalamus, has been widely recognised for its role in anxiolysis, bonding, sociality, and appetite. It binds to the oxytocin receptor (OXTR)-a G-protein coupled receptor-that is stimulated by the actions of oestrogen both peripherally and centrally. Studies have implicated OXTR genotypes in conferring either a risk or protective effect in autism, schizophrenia, and eating disorders (ED). There are numerous DNA variations of this receptor, with the most common DNA variation being in the form of the single nucleotide polymorphisms (SNPs). Two OXTR SNPs have been most studied in relation to ED: rs53576 and rs2254298. Each SNP has the same allelic variant that produces genotypes AA, AG, and GG. In this critical review we will evaluate the putative role of rs53576 and rs2254298 SNPs in ED. Additionally, this narrative review will consider the role of gene-environment interactions in the development of ED pathology.FindingsThe OXTR SNPs rs53576 and rs2254298 show independent associations between the A allele and restrictive eating behaviours. Conversely, the G allele of the OXTR rs53576 SNP is associated with binging behaviours, findings that were also evident in neuroanatomy. One study found the A allele of both OXTR SNPs to confer risk for more severe ED symptomatology while the G allele conferred some protective effect. An interaction between poor maternal care and rs2254298 AG/AA genotype conferred increased risk for binge eating and purging in women.ConclusionsIndividual OXTR SNP are unlikely in themselves to explain complex eating disorders but may affect the expression of and/or effectiveness of the OXTR. A growing body of G x E work is indicating that rs53576G homozygosity becomes disadvantageous for later mental health under early adverse conditions but further research to extend these findings to eating pathology is needed. The GWAS approach would benefit this area of knowledge.

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Contribution of oxytocin receptor polymorphisms to amygdala activation in schizophrenia spectrum disorders.

Publications

Contribution of oxytocin receptor polymorphisms to amygdala activation in schizophrenia spectrum disorders.

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