A novel perspective on biomarkers of neurodegeneration and neuroinflammation in first episode psychosis: a cross-sectional study.

BACKGROUND: The biological distinction between first-episode psychosis (FEP) and chronic schizophrenia remains unclear. This study investigated a panel of non-canonical serum biomarkers related to neurodegeneration, neuroinflammation, and neurotrophic signaling across these clinical stages. METHODS: In a cross-sectional design, serum concentrations of 18 biomarkers were measured using multiplex immunoassay in 49 FEP patients, 80 patients with chronic schizophrenia (SCH), and 80 healthy controls (CON). Principal component analysis identified two major axes (neuroinflammatory-neurotrophic and synaptic), but the distributions of diagnostic groups overlapped substantially. RESULTS: A distinct biomarker profile was identified in FEP, characterized by significantly lower levels of YKL-40 and BDNF, elevated NCAM-1, decreased TDP-43, and a higher frequency of detectable Aβ1‑42 compared to both SCH and CON groups. In contrast, the SCH group did not differ from CON on most of these markers. Correlation analysis revealed a dense, interconnected biomarker network in SCH, centered on MIF and BDNF, while FEP exhibited a single strong correlation between TDP-43 and YKL-40. Principal component analysis identified two major axes (neuroinflammatory-neurotrophic and synaptic) but showed substantial overlap between diagnostic groups. CONCLUSION: The findings reveal a unique, stage-dependent biological signature in early psychosis, differentiating FEP from both health and the chronic phase of illness. This supports the view of FEP as a distinct pathophysiological state involving dysregulated neuroinflammation, synaptic plasticity, and protein homeostasis, rather than merely a prodromal stage of chronic schizophrenia. CLINICAL TRIAL NUMBER: Not applicable.