Association between neutrophil to lymphocyte ratio and inflammatory biomarkers in patients with a first episode of psychosis

Neutrophil to lymphocyte ratio (NLR) has been proposed as an emerging marker of the immune system alterations in psychotic disorders. However, it is not entirely clear whether NLR elevation is a characteristic of the psychotic disorder itself, which inflammatory pathways activation is detecting, or which possible confounding variables could alter its interpretation. We aimed 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 97 patients with a first episode of psychosis (FEP) and 77 matched healthy controls (HC). In the FEP group, NLR values presented a moderate, positive correlation with the pro-inflammatory mediator Prostaglandin E2 levels (r = 0.36, p < 0.001) and a small but significant, positive correlation with cannabis use (r = 0.25, p = 0.017). After controlling for cannabis use, the association between NLR and PGE2 remained significant (beta = 0.31, p = 0.012). In the HC group, NLR values negatively correlated with body mass index (BMI, r = -0.24, p = 0.035) and positively correlated with tobacco use (r = 0.25, p = 0.031). These findings support a relationship between the elevation of NLR values and an elevated expression of proinflammatory pathways related to stress response in patients with a FEP. In addition, our study highlights the importance of considering variables such as cannabis or tobacco consumption, and BMI when interpreting the results of studies aimed to establish a clinical use of NLR. These considerations may help future research to use NLR as a reliable biomarker to determine immune system status in this population.