Document Type

Article

Publication Date

2025

Abstract

Systemic inflammation has been increasingly implicated in the pathophysiology of schizophrenia. The neutrophil-to-lymphocyte ratio (NLR), a readily available marker of systemic inflammation, has not been thoroughly investigated in large, demographically-matched schizophrenia cohorts. Using data from the All of Us Research Program, we analyzed participants with schizophrenia (n = 396) matched to controls (n = 396) by sex, race, and age. NLR was calculated as the ratio of each participant’s median neutrophil count to median lymphocyte count across all available measurements, excluding extreme values (NLR > 7). Distribution normality was assessed using the Shapiro–Wilk test, and group differences were evaluated with the Mann–Whitney U and Welch’s t-tests. Median NLR was significantly higher in schizophrenia compared to controls (2.07 vs. 1.83; Mann–Whitney U p = 0.0067, Welch’s t-test p = 0.0329), with both groups demonstrating non-normal distributions (Shapiro–Wilk p < 0.001). These findings indicate elevated systemic inflammation in schizophrenia and support the potential of NLR as a simple, scalable biomarker for immune dysregulation in the setting of acute psychosis, in addition to the broader course of the illness. Future work should explore NLR’s utility in tracking disease progression, treatment response, and relapse risk, ultimately bridging immune and psychiatric research toward more personalized care.

Comments

Preprint © 2025 the authors.

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