Oxytocin is a neuropeptide that plays a crucial role in human physiology and social behavior. However, the neurobiological mechanisms underlying the influence of oxytocin pathway gene variations and intranasal oxytocin on neural structure and connectivity remain unclear. This thesis set out to explore these mechanisms, aiming to deepen our understanding of how oxytocin influences brain structure, resting-state functional connectivity, and social function.

Study I examined the associations between variations in ten single nucleotide polymorphisms (SNPs) within three oxytocin pathway genes and whole-brain gray matter volume using data from the UK Biobank (N ≈ 30,000 subjects of relevance for the current studies). The results indicated that carriers of the AA or AG genotypes of the oxytocin receptor gene rs237851 SNP had significantly larger hippocampal volumes compared to carriers of the GG genotype. These findings support a link between variations in the oxytocin receptor gene and hippocampal structure, which may have implications for social-cognitive functions, such as social recognition memory.

Study II investigated the relationship between variations in ten SNPs in oxytocin pathway genes and resting-state functional connectivity among 55 independent components, again using data from the UK Biobank (N ≈ 30,000 subjects of relevance for the current studies). Findings revealed that individuals with the GG genotype at rs4813627 within the oxytocin structural gene (OXT) exhibited weaker resting-state functional connectivity in the corticostriatal circuit compared to those with the GA/AA genotypes. The GG genotype has been empirically linked to a behavioral tendency of insensitivity to others, providing insight into the neural mechanisms by which oxytocin-related genetic factors influence social behavior.

Study III explored the effects of intranasal oxytocin on resting-state functional connectivity, focusing on regions densely populated with oxytocin receptors. The study tested whether connections between oxytocin receptor-enriched regions (e.g., thalamus, pallidum, caudate nucleus, putamen, and olfactory bulbs) and other brain regions responded to intranasal oxytocin administration, and whether these effects varied with age. Results showed age-dependent effects of intranasal oxytocin on resting-state functional connectivity. In young participants, oxytocin decreased connectivity density and strength in the thalamus, whereas in older participants, it increased connectivity density and strength in the caudate. These findings highlight the age-dependent mechanisms of exogenous oxytocin on brain function.

Overall, this thesis explores the potential neurobiological mechanisms by which oxytocin pathway gene variations and intranasal oxytocin may influence brain structure and resting-state functional connectivity. These studies provide preliminary evidence on how oxytocin might affect social functions, offering insights for future research in neuropsychology and potential directions for interventions targeting social cognitive disorders.