Reduced serum levels of the pro-resolving lipid mediators resolvin D1 and lipoxin A4 in schizophrenia.

Schizophrenia is increasingly conceptualized as a disorder of chronic, unresolved neuroinflammation, yet why the inflammatory burden fails to resolve remains unclear. Specialized pro-resolving lipid mediators-including resolvin D1 (RvD1) and lipoxin A4 (LXA4)-actively terminate inflammation but have rarely been examined in schizophrenia. Because no previous study has measured LXA4 in schizophrenia or assessed both mediators concurrently, we compared serum RvD1 and LXA4 levels between patients and controls and assessed their association with illness severity. In this single-center case-control study, fasting serum RvD1 and LXA4 were measured by ELISA in 35 patients with schizophrenia (DSM-5) during an acute psychotic episode and 35 healthy controls of comparable age and sex; severity was rated with the PANSS and the Clinical Global Impression-Severity (CGI-S) scale. Both mediators were significantly lower in patients than controls (RvD1: 3372 ± 863 vs 3981 ± 382 ng/L, p < 0.001, Cohen's d = -0.91; LXA4: p = 0.002), and each remained independently associated with case status after adjustment for age, sex, and body mass index. Lower RvD1 correlated with higher CGI-S scores (ρ = -0.54, p = 0.001), whereas LXA4 did not. This provides preliminary evidence that circulating levels of these pro-resolving lipid mediators are reduced in schizophrenia, consistent with altered pro-resolving signalling rather than a demonstrated failure of the resolution process itself. Overall, they identify RvD1 as a candidate severity-related biomarker in patients during an acute psychotic episode, warranting confirmation in larger, longitudinal, mass spectrometry-based studies.