Despite significant advances in the field, many aspects of the pathophysiology of schizophrenia and related psychotic disorders remain unknown (Jauhar et al., 2022). An accumulation of scientific evidence supports the hypothesis that several processes involving inflammatory pathways and consequent oxidative/nitrosative stress are implicated, pointing to a persistent low-grade, pro-inflammatory state (Jauhar et al., 2022; Leza et al., 2015). This state appears both centrally and peripherally, starting from the initial phases of psychotic disorders (Fraguas et al., 2019; García-Bueno et al., 2014).

Neutrophil to lymphocyte ratio (NLR), calculated as a simple ratio between the neutrophil and lymphocyte counts measured in peripheral blood, has emerged as a potential marker of the intricate interplay between the immune system and a vast spectrum of diseases, including cancer, infections, and cardiovascular diseases (Buonacera et al., 2022; Li et al., 2018). Its accessibility and low cost make it an attractive option. Furthermore, it conjugates two faces of the immune system: the innate immune response, mainly due to neutrophils, and adaptive immunity, supported by lymphocytes (Buonacera et al., 2022; Song et al., 2021).

Two metanalysis have showed increased NLR values both in first episode of psychosis (FEP) and in multi-episodic schizophrenia (Karageorgiou et al., 2019; Mazza et al., 2020). Our group replicated these results in a FEP cohort, revealing that NLR differences between cases and control subjects increased over a 24-month follow-up period (Bioque et al., 2022). Notably, higher NLR values were associated to not achieving remission by the end of the study. A different metanalysis reported that neutrophils and monocytes were significantly increased in subjects with a FEP compared with controls (Jackson and Miller, 2020). Interestingly, we have also reported a connection between this systemic parameter and structural brain changes, associating isolated neutrophil count with reduced grey matter and enlarged ventricles in FEP (Núñez et al., 2019).

However, it is not entirely clear whether NLR elevation represents a primary characteristic of the psychotic disorder itself, or if treatment or metabolic changes could influence this value, or its relation with specific inflammatory pathways (Karageorgiou et al., 2019). Moreover, several major variables and conditions could determine a “false” increase in NLR values, including age, obesity, infections, diabetes, and emotional stress among others (Buonacera et al., 2022). Thus, the FEP population is of great interest since it could mitigate the impact of some of these confounding variables (Bernardo et al., 2013).

In this context, the current study aims to analyze the relationship of NLR values with a panel of inflammatory and oxidative/nitrosative stress biomarkers and main potential confounding factors in a well-characterized cohort of patients with a FEP and a matched control group.