Systemic inflammatory and oxidative stress alterations in recent-onset psychosis: findings from a non-smoking case-control sample

Background: Peripheral biomarkers of inflammation and oxidative stress have previously been implicated in psychosis. However, many studies do not account for cigarette smoking, despite its known impact on these pathways. Moreover, heterogeneous patient samples and limited consideration of clinical characteristics have made it difficult to disentangle which factors are truly related to the disease process. This study aimed to compare selected biomarkers between patients with recent-onset psychosis and matched controls in a non-smoking sample, and to explore associations with clinical characteristics. Methods: In this cross-sectional case-control study, 47 patients (mean age: 24.55 [3.80] years) with recent-onset psychosis (first episode less than 3 years ago) and 36 matched (on age, sex and ethnicity) controls were included. Plasma levels of free thiols, MMP-9, sCD163 and a panel of cytokines were measured. Group comparisons were conducted using the Wilcoxon rank-sum test. Associations with clinical and metabolic characteristics were examined using linear regression. Additional analyses were performed in the subgroup classified as having a schizophrenia spectrum disorder (SSD). Results: Patients with psychosis exhibited significantly higher MMP-9 levels than controls (p = 0.029, r = 0.28). Across groups, free thiol levels were negatively associated with waist circumference. IP-10 levels were associated with alcohol consumption, educational level and PANSS total score. In the SSD subgroup, additional associations emerged between free thiols and educational level, IP-10 and age, and TNF-α and glucose. Conclusions: MMP-9 levels are elevated in recent-onset psychosis, independent of smoking. Our findings underscore the importance of accounting for clinical and metabolic heterogeneity when interpreting peripheral biomarkers in psychosis.