A narrative review on oxytocin at the intersection of sleep, stress, and social behavior

Sleep, stress regulation, and circadian rhythms form an interdependent network that shapes cognition, emotion, and social behavior. Disruption of any component can amplify stress sensitivity and impair emotional regulation, leading to neurobehavioral instability. This review discusses evidence from human and animal studies to illustrate how oxytocin (OT) may function at multiple brain regions to modulate sleep regulation, stress physiology, and social interaction. We discuss mechanisms by which sleep deficiency heightens hypothalamic-pituitary-adrenal (HPA) axis activity and stress-related behavioral reactivity and impulsivity, and how OT signaling is thought to counteract these effects by reducing HPA output and stress-induced behavioral responses. Furthermore, converging evidence from preclinical and emerging human studies suggests that OT release may contribute to non-rapid eye movement (NREM) and rapid eye movement (REM) sleep stability potentially via modulation of hippocampal-amygdalar circuits and thalamocortical network activity, including sleep spindle-related dynamics, thereby enhancing emotional processing and social memory. Social isolation, a potent stressor, reduces OT signaling and disrupts sleep-wake dynamics, suggesting a mechanistic link between positive social interaction and sleep maintenance. Collectively, we propose OT as a key neuromodulatory regulator at the intersection of sleep, stress resilience, and social behavior, providing new insights into the neuroendocrine pathways that underlie adaptive emotional regulation and identifying potential therapeutic targets for stress-related sleep disturbances.