Serum B-cell activating factor and delayed memory in first-episode drug-naïve schizophrenia: a case-control study

Cognitive impairment in schizophrenia has been linked to immune dysregulation, but the role of humoral immune regulators remains unclear. We examined serum B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) in 90 first-episode drug-naïve schizophrenia (FES) patients and 90 matched healthy controls (HCs). Cognitive performance was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS). Serum BAFF and APRIL were measured using Luminex technology. After adjustment for age, sex, education, BMI, and smoking status, serum BAFF and APRIL levels were significantly lower in FES patients than in HCs (BAFF: F = 131.935, P < 0.001; APRIL: F = 59.772, P < 0.001). In the hypothesis-driven primary analytic model focusing on RBANS delayed memory, the Group × BAFF interaction was significant ( F (1,171) = 13.524, P < 0.001), with a positive BAFF slope in HCs ( B = 0.015, P = 0.017) but a negative slope in FES patients ( B = -0.022). This interaction remained robust in sensitivity analyses. Exploratory analyses suggested a nominal Group × BAFF interaction for RBANS total score ( F = 5.866, P = 0.016, FDR-adjusted q = 0.082), which was interpreted cautiously. No analogous Group × APRIL interaction was observed, and BAFF/APRIL levels were not significantly associated with PANSS symptom dimensions. These cross-sectional findings identify peripheral BAFF as a hypothesis-generating correlate of delayed memory in early untreated schizophrenia, but do not establish temporality, causality, or central immune-cognitive mechanisms.