Abstract
INTRODUCTION: Neuroinflammation is increasingly recognized as a core pathophysiological mechanism in schizophrenia and can be indirectly assessed through peripheral inflammatory markers. Therefore, this pilot study investigated the impact of antipsychotic treatment on inflammation in patients with first-episode psychosis (FEP) who were antipsychotic-naive at study entry. METHODS: Thirty-three drug-naïve FEP patients provided blood samples upon admission (V0) and follow-up (V1), from which peripheral inflammatory markers-i.e., neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)-were calculated. Antipsychotic doses during continuous hospitalization between V0 and V1 (34 days, IQR: 21-49 days) were converted into cumulative chlorpromazine equivalents (cCPZ). RESULTS: In multiple regression models adjusting for sex, age, BMI, DUP, and clozapine use, cumulative antipsychotic exposure significantly predicted reductions in ΔNLR (p = 0.048), ΔMLR (p = 0.041), ΔPLR (p = 0.028), and ΔSII (p = 0.028). All associations remained significant following false discovery rate adjustment (pFDR = 0.048 for all outcomes). CONCLUSION: These findings suggest a consistent dose-dependent anti-inflammatory effect during early antipsychotic treatment in FEP. Given the exploratory nature of this study, larger studies are needed to confirm these findings.