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

Davis, Michael C.; Horan, William P.; Nurmi, Erika L.; Rizzo, Shemra; Li, Wendy; Sugar, Catherine A.; Green, Michael F.

doi:10.1016/j.schres.2014.09.006

Cited by 36 publications

(30 citation statements)

References 49 publications

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“…Subsequently, Campbell et al (2011) used a narrow diagnosis of autism in an Autism Genetic Resource Exchange (AGRE) sample and found rs2268493T to be significantly associated with their diagnosis criteria. In schizophrenia, rs2268493T has also been associated with social cognition (Davis et al, 2014). Decreased activity in the mesolimbic reward circuitry during reward anticipation in typically-developed adults was associated with the T homozygotes of rs2268493 (Damiano et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…There is a growing literature about OT and AVP in a range of disorders including schizophrenia, COMD, bipolar disorder as well as neurodevelopmental disorders (Dempster et al, 2007; Leszczynska-Rodziewicz et al, 2012; Davis et al, 2014; Francis et al, 2014). There are currently many clinical trials exploring the therapeutic value of OT and AVP (e.g., in ASD, schizophrenia, major depressive disorder, and substance dependence).…”

Section: Discussionmentioning

confidence: 99%

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ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin—AVPR1A, AVPR1B, and OXTR

et al. 2016

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Background: There are limited treatments available for autism spectrum disorder (ASD). Studies have reported significant associations between the receptor genes of oxytocin (OT) and vasopressin (AVP) and ASD diagnosis, as well as ASD-related phenotypes. Researchers have also found the manipulation of these systems affects social and repetitive behaviors, core characteristics of ASD. Consequently, research involving the oxytocin/vasopressin pathways as intervention targets has increased. Therefore, further examination into the relationship between these neuropeptides and ASD was undertaken. In this study, we examined associations between variants in the receptor genes of vasopressin (AVPR1A, AVPR1B), oxytocin (OXTR), and ASD diagnosis along with related subphenotypes.Methods: Probands were assessed using Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, and clinical DSM-IV-TR criteria. Single nucleotide polymorphisms (SNPs) in AVPR1B and OXTR, and microsatellites in AVPR1A were genotyped in ~200 families with a proband with ASD. Family-based association testing (FBAT) was utilized to determine associations between variants and ASD. Haplotypes composed of OXTR SNPs (i.e., rs53576-rs2254298-rs2268493) were also analyzed due to previously published associations.Results: Using the additive inheritance model in FBAT we found associations between AVPR1B SNPs (rs28632197, p = 0.005, rs35369693, p = 0.025) and diagnosis. As in other studies, OXTR rs2268493 (p = 0.050) was associated with diagnosis. rs2268493 was also associated with ASD subphenotypes of social withdrawal (p = 0.013) and Insistence on Sameness (p = 0.039). Further analyses demonstrated that the haplotype, rs2254298–rs2268493 was found to be significantly associated with diagnosis (A-T; p = 0.026). FBAT was also used to analyze AVPR1A microsatellites (RS1 and RS3). Both length variants were found to be associated with restrictive, repetitive behaviors, but not overall diagnosis. Correction for multiple comparisons was performed for SNPs tested in each gene region, only AVPR1B SNPs remained significantly associated with ASD diagnosis.Conclusions: Autism is a heterogeneous disorder with many genes and pathways that contribute to its development. SNPs and microsatellites in the receptor genes of OT and AVP are associated with ASD diagnosis and measures of social behavior as well as restricted repetitive behaviors. We reported a novel association with ASD and AVPR1B SNPs. Understanding of genotype-phenotype relationships may be helpful in the development of pharmacological interventions for the OT/AVP system.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin—AVPR1A, AVPR1B, and OXTR

et al. 2016

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“…Recent evidence suggests that intranasal oxytocin may also improve general cognition in schizophrenia [12,13,14,15]. In addition, genetic variants of the oxytocin receptor gene ( OXTR) , which serves as the binding point for oxytocin action through second messenger systems in the brain, have been linked to a diagnosis of schizophrenia [16] and poorer cognitive performance in psychotic disorders [17,18]. Thus, the genetic regulation of oxytocin pathways via deoxyribonucleic acid (DNA) variation, and its relationship to cognition in schizophrenia continues to be an active area of research [for review, see [19]].…”

Section: Introductionmentioning

confidence: 99%

Oxytocin Receptor <b><i>(OXTR)</i></b> Methylation and Cognition in Psychotic Disorders

et al. 2016

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Previous reports have identified an association between cognitive impairment and genetic variation in psychotic disorders. In particular, this association may be related to abnormal regulation of genes responsible for broad cognitive functions such as the oxytocin receptor (OXTR). Within psychotic disorders, it is unknown if OXTR methylation, which can have important implications for gene regulation, is related to cognitive function. The current study examined peripheral blood OXTR methylation and general cognition in people with schizophrenia, schizoaffective disorder, and psychotic disorder not otherwise specified (N = 101). Using hierarchical multiple regression analysis, methylation at the Chr3:8767638 site was significantly associated with composite cognitive performance independent of demographic and medication factors while controlling for multiple testing in this combined diagnostic sample (adjusted p = 0.023).

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“…Adjunctive exogenous OT administration can improve social cognition in schizophrenia (15-19). Preliminary data suggests that social cognitive deficits in schizophrenia have been linked to OXTR polymorphisms (20, 21). However to date, no studies have examined epigenetic regulation of the OXTR and its relation to OT levels in psychotic disorders, social cognition or neuroanatomical structures important for social cognition including temporal-limbic regions where OXTR concentrations are high (22).…”

mentioning

confidence: 99%

Sex and Diagnosis-Specific Associations Between DNA Methylation of the Oxytocin Receptor Gene With Emotion Processing and Temporal-Limbic and Prefrontal Brain Volumes in Psychotic Disorders

Rubin

Connelly

Reilly

et al. 2016

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

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Background The oxytocin (OT) system, including receptor epigenetic mechanisms, has been shown to influence emotion processing, especially in females. Whether OT receptor (OXTR) epigenetic alterations occur across psychotic disorders in relation to illness-related disturbances in social cognition and brain anatomy is unknown. Methods Participants with affective and nonaffective psychotic disorders (92 women, 75 men) and healthy controls (38 women, 37 men) from the Chicago site of the BSNIP study completed the Penn Emotion Recognition Test (ER-40), a facial emotion recognition task. We measured cytosine methylation at site -934 upstream of the OXTR start codon in DNA from whole blood, and for the first time their relationship with plasma OT levels assessed by enzyme-immunoassay. Volumes of brain regions supporting social cognition were measured from MRI scans using FreeSurfer. Results Patients with prototypic schizophrenia features showed higher levels of DNA methylation than those with prototypic bipolar features. Methylation was higher in women than men, and was associated with poorer emotion recognition only in female patients and controls. Greater methylation was associated with smaller volumes in temporal-limbic and prefrontal regions associated previously with social cognition, but only in healthy women and females with schizophrenia. Conclusion DNA methylation of the OXTR site -934 was higher in schizophrenia spectrum than bipolar patients. Among patients, it was linked to behavioral deficits in social cognition and neuroanatomic structures known to support emotion processing only in schizophrenia spectrum individuals.

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

Cited by 36 publications

References 49 publications

ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin—AVPR1A, AVPR1B, and OXTR

ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin—AVPR1A, AVPR1B, and OXTR

Oxytocin Receptor <b><i>(OXTR)</i></b> Methylation and Cognition in Psychotic Disorders

Sex and Diagnosis-Specific Associations Between DNA Methylation of the Oxytocin Receptor Gene With Emotion Processing and Temporal-Limbic and Prefrontal Brain Volumes in Psychotic Disorders

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