Bilirubin and Inflammatory Biomarkers in Substance-Induced Psychosis: a Real-World Pilot Study

Background: Substance-induced psychosis (SIP) has been associated with inflammatory and oxidative alterations, although the biological mechanisms underlying this condition remain incompletely understood. Peripheral biomarkers such as bilirubin, C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR) may provide preliminary insight into these processes in real-world psychotic populations with polysubstance use. Methods: This retrospective pilot study included 29 patients with SIP and polysubstance use, predominantly involving cannabis and cocaine. Associations between bilirubin, CRP, complete blood count–derived inflammatory ratios, duration of untreated psychosis (DUP), and symptom profiles were explored using Spearman’s correlation and Kruskal–Wallis analyses. Results: A strong positive correlation was observed between bilirubin and CRP levels (ρ = 0.87, p < 0.001). NLR showed a moderate positive association with DUP (ρ = 0.41, p = 0.039). Bilirubin levels also differed significantly across symptom clusters, with higher values observed in patients presenting predominantly disorganized symptoms (H = 7.032, p = 0.030). No significant associations emerged for other inflammatory ratios. Conclusions: These preliminary findings suggest possible associations between peripheral inflammatory markers, oxidative-related biomarkers, and clinical features in SIP. However, given the small retrospective sample, the exploratory nature of the analyses, and potential confounding factors related to polysubstance use and clinical heterogeneity, the findings should be interpreted cautiously. Further prospective studies with larger and better-characterized samples are needed to clarify the potential clinical relevance of bilirubin and related inflammatory biomarkers in SIP.