Clinical Relevance of Peripheral Interleukins in Drug-Naive First-Episode Psychosis: Symptom-Specific Associations from the PANSS Dimensions

<b>Background/Objectives</b>: Emerging evidence suggests a role of immune-inflammatory mechanisms in the pathophysiology of schizophrenia, particularly in the early stages of the illness. Cytokines, as key mediators of inflammation, may affect brain function and clinical presentation. Drug-naive patients with first-episode psychosis (FEDN) offer a unique opportunity to investigate these associations free from confounding pharmacological effects. <b>Methods</b>: This study included 38 patients with drug-naive first episode psychosis and 22 age- and sex-matched healthy controls. Serum concentrations of IL-1β, IL-2, IL-6, and IL-10 were measured using ELISA. Clinical symptoms were assessed using the PANSS scale. Statistical analyses included Mann-Whitney U tests, Spearman's correlations, and ROC curve analysis. <b>Results</b>: Significantly elevated serum levels of IL-1β, IL-2, and IL-10 were observed in the FEDN group compared to the controls (<i>p</i> < 0.01), while IL-6 levels did not differ significantly. IL-2 exhibited the highest discriminatory power in differentiating the patients from the controls (AUC = 0.917; 95% CI: 0.759-1000.0; <i>p</i> < 0.001). IL-1β levels positively correlated with negative and general psychopathology symptoms, including hostility and grandiosity. IL-10 was associated with volitional disturbance and overall PANSS severity. <b>Conclusions</b>: Our findings underscore the relevance of immune dysregulation in the early stages of psychosis and highlight the potential of specific cytokines, particularly IL-2 and IL-1β, as peripheral biomarkers. Their diagnostic utility and correlation with symptom dimensions suggest a promising role in the development of precision psychiatry approaches, including early detection strategies and individualised therapeutic targeting. Longitudinal studies are needed to validate these findings and to assess their prognostic significance.