301. OXYTOCIN AS A POTENTIAL BIOMARKER FOR METABOLIC SYNDROME IN SCHIZOPHRENIA

Abstract Background The rising prevalence of metabolic syndrome (MetS) and its associated morbidity in schizophrenia has spurred research into shared pathophysiological mechanisms. Overlapping features, such as cognitive dysfunction, autonomic dysregulation, altered resting-state networks, and genetic predispositions, point to oxytocin system dysfunction as a potential link between schizophrenia and MetS. Additionally, early-life adversity, particularly childhood trauma, may have lasting effects on stress-response systems, reducing oxytocin levels and increasing metabolic vulnerability. Understanding these interactions could illuminate neuroendocrine pathways and guide preventive strategies. Aims & Objectives We aimed to explore the relationships among childhood trauma, plasma oxytocin levels, and MetS in persons with schizophrenia, with a focus on whether these factors predict MetS progression. Additionally, it examined the potential mediating role of plasma oxytocin in the link between childhood trauma and metabolic risk. Method This 24-month prospective cohort study enrolled 90 persons with schizophrenia on stable monotherapy and 60 age- and gender-matched healthy controls. Data on anthropometric measures, metabolic parameters, and plasma oxytocin levels were collected at baseline and follow-up. Childhood trauma was retrospectively evaluated using the Childhood Trauma Questionnaire-Short Form (CTQ-SF). Results At baseline, plasma oxytocin levels were significantly lower in persons with schizophrenia compared to healthy controls (p < .001), and this difference remained significant after 24 months. Among persons with schizophrenia, higher levels of childhood trauma were associated with lower baseline oxytocin levels (p = .001), higher BMI (p < .001), and more metabolic risk factors (, p = .009). Over 24 months, the incidence of metabolic syndrome was higher in persons with schizophrenia than in healthy controls (0.253 vs. 0.117; p = .043). Persons with schizophrenia also showed significant increases in BMI, systolic and diastolic blood pressure, waist circumference, triglycerides, and fasting glucose (all p < .05), whereas only HDL levels decreased significantly in healthy controls (p = .035). The GEE analysis revealed that the odds of developing MetS increased by 48% over 24 months compared to baseline (OR = 1.48, p < .001). Plasma oxytocin levels were negatively associated with MetS risk, reducing the odds by 73% (p = .009). The interaction between CTQ-SF and oxytocin was significant (OR = 0.95, p = .018), indicating that higher oxytocin levels mitigated the effect of childhood trauma on MetS risk, after adjusting for sex, age of onset, duration of treatment, and antipsychotic medication type. Discussion & Conclusions These findings suggest that childhood trauma may contribute to long-term metabolic vulnerability in schizophrenia through oxytocin dysregulation. Specifically, persons with schizophrenia exhibited lower baseline oxytocin levels and a greater increase in metabolic risk over time compared to healthy controls. The negative association between childhood trauma and plasma oxytocin levels, combined with the observed interaction effect—where higher oxytocin levels mitigated the impact of trauma on metabolic risk—supports the hypothesis that oxytocin may serve as a protective factor against trauma-related metabolic dysfunction. This highlights the potential role of oxytocin as an endophenotypic marker of trauma-related metabolic susceptibility and underscores its therapeutic potential. Future studies should investigate the mechanisms underlying this interaction and explore interventions aimed at enhancing oxytocin function to reduce metabolic risk.