Clinical correlates and cognitive associations of the neutrophil-to-lymphocyte ratio in first-episode psychosis and at-risk mental states.

Objective: Clinical high-risk for psychosis (CHR-P) and first-episode psychosis (FEP) individuals present immune alterations that precede treatment initiation. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a simple, accessible marker of systemic inflammation. This study investigates differences across CHR-P, FEP, and healthy control (HC) populations and explores peripheral associations between NLR and demographic, clinical, and cognitive variables. Methods: Data were collected from 63 FEP, 56 CHR-P, and 27 HC individuals from two early intervention services in Spain. Socio-demographic, clinical, and neurocognitive data were collected from all participants, along with peripheral blood samples for NLR calculation. Correlations between NLR and clinical and neurocognitive variables were analyzed using multivariate models to control for potential confounders. Results: No significant differences in NLR were observed between the FEP, CHR-P, and HC groups (F = 1.04; p=0.36). In the FEP population, NLR was positively correlated with higher levels of positive symptoms (β=0.035; p=0.01) and longer duration of untreated psychosis (β=0.003; p=0.04) after adjusting for sex and age. In CHR-P individuals, NLR was negatively correlated with antidepressant use (β=-0.664; p=0.02). No significant associations were found between NLR and neurocognitive performance or antipsychotic treatment in any clinical group. Conclusions: Our findings do not support the utility of NLR as a diagnostic biomarker in early psychosis. However, the observed association between elevated NLR and positive psychotic symptoms in FEP suggests that NLR could serve as a state biomarker, reflecting inflammatory status related to symptom severity. Further research is needed to explore NLR dynamics in larger samples and its potential role in monitoring clinical progression in psychosis.