Translational pathways of oxytocin therapy in schizophrenia: bridging negative symptom domains and neural mechanisms.

Negative symptoms of schizophrenia, characterized by motivational deficits, diminished hedonic experience, and impaired affective expression, remain a major therapeutic challenge. Oxytocin, a neuropeptide with central nervous system activity, has emerged as a promising therapeutic target due to the close alignment of its functions with the pathophysiological mechanisms underlying negative symptoms. Based in the dimensional model of negative symptoms, this review systematically synthesizes advances in understanding the physiological functions of the oxytocin system and its therapeutic potential for negative symptoms in schizophrenia, with a focus on its multi-target neural mechanisms. Oxytocin exerts its effects through coordinated modulation of multiple neural circuits: enhancing mesolimbic dopamine pathway function to improve social reward processing and facilitating motivation via the prefrontal-striatal circuit, while stabilizing the amygdala-prefrontal emotional circuit and modulating the sensorimotor integration network and prefrontal motor pathway to ameliorate affective expression deficits. Current evidence highlights the therapeutic potential of oxytocin; however, clinical findings demonstrate marked heterogeneity, suggesting that its translation still requires overcoming multiple challenges. Future research should integrate genetic, neuroimaging, and behavioral paradigms to identify oxytocin-sensitive subtypes, optimize administration strategies, and coordinate behavioral interventions, thereby advancing the translation of oxytocin toward precision psychiatry in schizophrenia.