Methylation of OXT and OXTR genes, central oxytocin, and social behavior in female macaques

• Authors: Desirée De Leon, Emory University; Shota Nishitani, Emory University; Hasse Walum, Emory University; Kai McCormack, Emory University; Mark Wilson, Emory University; Alicia Smith, Emory University; Larry Young, Emory University; Maria Sanchez, Emory University
• Journal Title: HORMONES AND BEHAVIOR
• Volume: Volume 126
• Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE | 2020-11-01, Pages 104856-104856
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.yhbeh.2020.104856
• Subjects: Health Sciences, Obstetrics and Gynecology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Behavioral Sciences; Endocrinology & Metabolism; Epigenetics; Rhesus; Oxytocin receptor; DNA methylation; MT2 region; Nonhuman primates; RECEPTOR GENE; DNA METHYLATION; NEUROANATOMICAL DISTRIBUTION; RHESUS-MONKEYS; TISSUE; EXPRESSION; PROMOTER; BLOOD; INTRANASAL; AGGRESSION

Abstract

Oxytocin (OXT) and its receptor (OXTR) are encoded by OXT and OXTR, respectively. Variable methylation of these genes has been linked to variability in sociability and neuroendophenotypes. Here we examine whether OXTR or OXT methylation in blood predicts concentrations of OXT in cerebrospinal fluid (CSF) (n = 166) and social behavior (n = 207) in socially-housed female rhesus macaques. We report a similarity between human and rhesus CpG sites for OXT and OXTR and a putative negative association between methylation of two OXTR CpG units with aggressive behavior (both P = 0.003), though this finding does not survive the most stringent correction for multiple comparison testing. We did not detect a statistically significant association between methylation of any CpG sites and CSF OXT concentrations, either. Because none of the tested associations survived statistical corrections, if there is any relationship between blood-derived methylation of these genes and the behavioral and physiological outcomes measured here, the effect size is too small to be detected reliably with this sample size. These results do not support the hypothesis that blood methylation of OXT or OXTR is robustly associated with CSF OXT concentration or social behavior in rhesus. It is possible, though, that methylation of these loci in the brain or in cheek epithelia may be associated with central OXT release and behavior. Finally, we consider the limitations of this exploratory study in the context of statistical power.