OXT_AVP_PLC_fmridata

Witnessing social distress of others evokes social pain empathy. Although hypothalamic neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) are known to play roles in social function, their respective contributions to the process of social pain empathy have not been systematically understood. Here, we combined naturalistic fMRI with functional decoding, gene expression, and pharmacological modulation using intranasal administration of OXT (24 IU) or AVP (20IU) to explore their neurobiological mechanisms underlying social pain empathy in a cohort of 103 participants. Our findings indicated that both OXT and AVP significantly enhanced pain empathy compared to placebo, with overlapping and distinct modulations in neurofunctional circuits and gene expressions. Specially, both neuropeptides altered emotional processing in the regions such as insula, amygdala, and para-hippocampus. Additionally, OXT and AVP induced distinguishable effects on resting-state functional connectivity, their respective gene receptors, and their interactions with other genetic systems. Our work provides a comprehensive characterization of these two hypothalamic neuropeptides in social pain empathy and offers valuable insights for future translational research.