Abstract
Brain Behav Immun Health. 2025 Nov 4;50:101134. doi: 10.1016/j.bbih.2025.101134. eCollection 2025 Dec.
ABSTRACT
BACKGROUND: Early diagnosis of psychosis is crucial, and biomarker detection may provide insights into the pathophysiology of psychosis and the potential for the development of early diagnostic tools. In particular, blood-based proteomic profiling has yielded promising results for psychiatric disorders because of the use of novel high-throughput techniques and the feasibility of performing blood extractions in routine clinical practice.
STUDY DESIGN AND METHODOLOGY: Here, we studied 182 participants (33.3 % females, X ‾ age = 24.66 ± 5.05), comprising 50 healthy controls (HCs), 37 patients with an at-risk mental state (ARMS) and 95 patients with a first episode of psychosis (FEP). We used a panel of 92 neurology-related proteins in a multiplex immunoassay to identify the plasma protein profiles of each group, their coexpression patterns and biological relevance, and their associations with psychotic symptoms and cognitive performance.
RESULTS: CPA2 was overexpressed in both ARMS participants (β = 0.876, adj. p = 0.009) and FEP participants (β = 0.568, adj. p = 0.011) compared with HCs. In FEP participants, in addition to CPA2, 31 other proteins were overexpressed, with GFRA1 being the most differentially expressed protein (β = 1.159, adj. p < 0.001). Coexpression clusters in FEP patients were involved in several biological processes, such as the regulation of myelination, cell adhesion, multicellular organismal processes and axon guidance. In ARMS patients, THY1 expression was inversely correlated with symptom severity (ρ = -0.640, adj. p = 0.039), and IL12 expression was correlated with cognitive performance (ρ = 0.707, adj. p = 0.007); however, no further correlations were found after the false discovery rate adjustment.
CONCLUSIONS: Our findings suggest the involvement of CPA2, GFRA1 and IL12, among other neurology-related proteins, in the early phases of psychosis, which, if confirmed, could become promising biomarkers for diagnosis, psychotic symptom development and psychosis-associated cognitive impairment. However, future studies with larger samples, a longitudinal design, and more extensive proteomic panels are needed to validate these biomarkers and refine their clinical applicability.
PMID:41311686 | PMC:PMC12648619 | DOI:10.1016/j.bbih.2025.101134
UK DRI Authors
