Impact of atypical antipsychotics on cytokine profiles in schizophrenia: An 8-week longitudinal study

Schizophrenia has traditionally been conceptualized through dopaminergic and glutamatergic frameworks. In recent years, attention has increasingly focused on the role of immune dysregulation in its pathophysiology, although conclusive evidence remains limited. In this context, the present study aimed to investigate alterations in cytokine profiles and their association with clinical symptomatology following treatment with atypical antipsychotics for 8 weeks.

Thirty patients aged 18-65 years, diagnosed with schizophrenia as per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, were enrolled. Participants received atypical antipsychotic therapy as clinically indicated. Symptom severity was assessed using the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS). Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), and regulated upon activation, normal T-cell expressed and secreted (RANTES) were measured at baseline and after 8 weeks of therapy.

Median SAPS and SANS scores significantly decreased from 39 to 30.5 (P < 0.001) and from 30 to 28 (P < 0.001), respectively. Correspondingly, median serum TNF-α levels declined from 28.55 (6.51-227) to 19.98 (4.56-145) pg/mL (P = 0.033). Reductions were also observed for IL-8 (62.2-50.25 pg/mL; P = 0.171) and RANTES (520-500 pg/mL; P = 0.758).

Treatment with atypical antipsychotics significantly attenuated both positive and negative symptoms and reduced TNF-α levels in patients with schizophrenia. The concomitant decline in cytokine concentrations suggests a potential immunomodulatory effect of treatment, highlighting TNF-α, IL-8, and RANTES as possible prognostic biomarkers.