Neuropeptide Y Levels Are Elevated in First-Episode Schizophrenia, but the Link to Symptoms Differs by Sex

Serum NPY levels were significantly higher in first-episode schizophrenia patients than controls (p<0.001). In males, NPY positively correlated with PANSS symptom scores at baseline (p<0.01) and changes in NPY tracked with symptom changes during risperidone treatment (p<0.05). No such correlations were found in females. The NPY × sex interaction was highly significant (p<0.001).

Case-control cohort study with 115 first-episode schizophrenia patients and 58 matched healthy controls. Serum NPY measured at baseline and after 10 weeks of risperidone treatment in patients. Symptoms assessed with the Positive and Negative Syndrome Scale (PANSS). 95 patients completed the full study protocol.

Understanding sex differences in schizophrenia has been a long-standing challenge. This study provides concrete biological evidence that neuropeptide Y — a molecule involved in stress response and brain signaling — behaves differently in male versus female schizophrenia patients. This could eventually lead to sex-specific treatment approaches.

Schizophrenia affects men and women differently in onset, symptom profiles, and treatment response, but the biological reasons remain unclear. NPY's sex-specific role in symptom severity adds to growing evidence that schizophrenia may involve partially different biological pathways in males and females, which has implications for developing more targeted treatments.

Moderate sample size with only 95 completing follow-up. All patients were treated with risperidone, so findings may not generalize to other antipsychotics. Serum NPY may not fully reflect brain NPY levels. The study didn't control for potential confounders like hormonal status in female patients. First-episode patients may differ from chronic schizophrenia populations.