Associations between oxytocin receptor genotypes and social cognitive performance in individuals with schizophrenia

Abstract

Individuals with schizophrenia often show substantial deficits in social cognitive abilities, which are strongly associated with social functioning. To advance our understanding of the genetic variation that is associated with social cognitive deficits in schizophrenia, we genotyped 74 schizophrenia outpatients who completed social cognitive performance measures assessing mentalizing, social perception, and emotional intelligence, as well as clinical symptoms. We assessed seven single nucleotide polymorphisms (SNPs) of the oxytocin receptor (OXTR) previously found to show replicable associations with socio-emotional processes. For one of the seven SNPs, rs2268493, the ‘T’ allele was significantly associated with poorer performance on a composite social cognition index, as well as specific tests of mentalizing and social perception. None of the SNPs were associated with clinical symptoms. Though the sample size is small, these findings provide initial support for the involvement of genetic variants of the OXTR in social cognitive impairments in schizophrenia.

Introduction

Individuals with schizophrenia often show marked deficits in social cognitive abilities, and these deficits are predictive of poor functioning (Fett et al., 2011, Horan et al., 2012). However, the mechanisms underlying impaired social cognition and its variability across patients are largely unknown. One possible contributor is the oxytocin system, which plays an important role in social cognition and behaviors in humans and other animals (Meyer-Lindenberg et al., 2011). This system is of particular interest in schizophrenia, given several recent studies suggesting potential use of intranasal oxytocin as a therapeutic agent (MacDonald and Feifel, 2012).

Many genetic studies have investigated the role of the oxytocin system in social processes, primarily in healthy individuals, and most have focused on genetic variation of the oxytocin receptor (OXTR) (Ebstein et al., 2012). The two most widely studied single nucleotide polymorphisms (SNPs) of the OXTR are rs53576 and rs2254298. These SNPs have frequently shown associations with empathy and various pro-social behaviors, though not all studies have supported such links (Bakermans-Kranenburg and van Ijzendoorn, 2014). Other OXTR SNPs have also shown replicable associations with similar pro-social behaviors (Kumsta and Heinrichs, 2013).

In schizophrenia research, several OXTR SNPs have shown initial associations with the schizophrenia diagnosis in case–control studies (Souza et al., 2010b, Watanabe et al., 2012, Montag et al., 2013b), as well as with symptom severity and response to clozapine therapy (Souza et al., 2010a, Montag et al., 2012, Montag et al., 2013b). Very little is known about the relationship of OXTR in schizophrenia and social cognition. Only one previous report examined this connection and used a self-report measure of empathy. That study found schizophrenia patients with an ‘A’ allele of rs2254298 scored higher on one subscale (i.e., Empathic Concern) than those with the ‘GG’ genotype (Montag et al., 2012).

Given the potential importance of genetic variation in the OXTR and the limited knowledge of its role in schizophrenia, we genotyped seven OXTR SNPs in schizophrenia patients who had been characterized on social cognitive performance measures. The seven SNPs were chosen based on their replicated associations with socio-emotional processing variables in prior studies. Considering the relatively small sample size, we view these findings as hypothesis-generating for future larger studies.