Oxytocin Modulates Multiple Neural Circuits to Improve Negative Symptoms in Schizophrenia

Negative symptoms of schizophrenia, characterized by motivational deficits, diminished hedonic experience, and impaired affective expression, remain a major therapeutic challenge. Standard treatments often fall short for these debilitating symptoms. 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 these deficits, making it a compelling candidate to bridge this therapeutic gap.

This systematic review synthesized advances in understanding the physiological functions of the oxytocin system and its therapeutic potential for negative symptoms in schizophrenia. Based on the dimensional model of negative symptoms, the authors integrated findings to highlight multi-target neural mechanisms. They focused on how oxytocin modulates specific brain circuits to address motivational deficits, social reward processing, and affective expression, drawing from various research paradigms.

The review elucidated how oxytocin exerts its effects through coordinated modulation of multiple neural circuits.

It enhances mesolimbic dopamine pathway function, improving social reward processing, and facilitates motivation via the prefrontal-striatal circuit. Additionally, oxytocin stabilizes the amygdala-prefrontal emotional circuit and modulates the sensorimotor integration network and prefrontal motor pathway, thereby ameliorating deficits in affective expression. Current evidence underscores the therapeutic potential of oxytocin; however, clinical findings demonstrate marked heterogeneity, suggesting challenges in its translation to consistent patient outcomes.