¹Yonsei University College of Medicine, Yongin Severance Hospital, Department of Psychiatry, Yongin, Korea, Republic of, ²Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Section of Self, Affect and Neuroscience, Seoul, Korea, Republic of, ³Yonsei University College of Medicine, Severance Hospital, Department of Psychiatry, Seoul, Korea, Republic of, ⁴Yonseialways Psychiatry Clinic, Department of Psychiatry, Seoul, Korea, Republic of

Background: Social cognition encompasses a wide range of abilities, from recognizing social cues to performing complex inferential reasoning, and is influenced by both environmental factors and epigenetic modifications. Prior research has shown that methylation changes in stress-responsive genes, such as brain-derived neurotrophic factor (BDNF) and the oxytocin receptor (OXTR), are associated with variations in social cognitive performance and demonstrate sex-specific patterns. This study explores the influence of these methylation differences on social cognition across sexes, considering both perceptual and inferential cognitive domains.

Aims & Objectives: This study investigates whether DNA methylation in stress-related genes like BDNF and OXTR is associated with social cognition at perceptual and inferential levels and how these relationships differ by sex. By exploring these interactions, the research aims to clarify the mechanisms through which sex influences the epigenetic modulation of social cognitive processes.

Method: Social cognition was evaluated using two measures: the Korean version of the Reading the Mind in the Eyes Test (K-RMET) for perceptual social cognition and Brune’s Theory of Mind Picture Stories Test (ToM-PST) for inferential social cognition. DNA methylation in BDNF and OXTR genes was analyzed, and statistical models tested the moderating role of sex in the association between methylation levels and social cognitive performance in a cohort comprising both male and female participants.

Results: While no significant correlations between DNA methylation and social cognition were observed across the entire sample, analysis revealed sex-specific associations. Specifically, higher BDNF methylation levels were linked to lower K-RMET scores in males, whereas increased OXTR methylation was negatively associated with ToM-PST scores in females.

Discussion & Conclusions: These findings highlight the nuanced relationship between epigenetic modifications and social cognitive functions, emphasizing sex-specific differences. The study underscores the importance of incorporating sex as a critical factor in epigenetic research on social cognition and suggests potential implications for developing tailored, sex-specific therapeutic strategies.