How does oxytocin modulate human behavior?

While the highly evolutionarily conserved hypothalamic neuropeptide, oxytocin (OT) can influence cognitive, emotional and social functions, and may have therapeutic potential in disorders with social dysfunction, it is still unclear how it acts. Here, we review the most established findings in both animal model and human studies regarding stimuli which evoke OT release, its primary functional effects and the mechanisms whereby exogenous administration influences brain and behavior. We also review progress on whether OT administration can improve social symptoms in autism spectrum disorder and schizophrenia and consider possible impediments to translational success. Importantly, we emphasize that OT acting via its extensive central or peripheral receptors primarily influences behavior indirectly through neuromodulatory interactions with classical transmitters and other peptides which themselves can independently influence behavior. We also emphasize that exogenous administration studies increasingly demonstrate peripheral effects of OT may be of greater importance than originally thought, especially involving the vagus. Overall, we propose a hierarchical model whereby OT's neuromodulatory actions influence behavior across interconnected functional domains and ultimately help to promote survival, security and sociability. Initially, OT potently facilitates attention to salient social and other important stimuli and additionally modulates cognitive, emotional and reward processing in a person- and context-dependent manner to promote interpersonal social understanding, attraction and bonds on the one hand and social group cohesion through increased conformity, altruistic punishment and moral emotions on the other. OT also increases co-operation and protection across both social domains. We hope this review and model will promote further research and help aid future translation success.