¹Peking University Sixth Hospital, Clinical Research Department, Beijing, China, ²Nanjing Brain Hospital affiliated to Nanjing Medical University, Department of Psychiatry, Nanjing, China

Background: Autoimmune dysfunction plays a crucial role in the pathogenesis of schizophrenia, with abnormalities in peptide antigen-related IgG levels observed in patients, significantly differing from those in healthy individuals. Although previous studies have suggested a correlation between peptide antigen-related IgGs and the symptoms of schizophrenia, research on the relationship between these IgGs and treatment outcomes in first-episode schizophrenia (FES) patients remains insufficient.

Aims & Objectives: This study examined the relationship between changes in peptide antigen-related IgG levels and one-year treatment outcomes in FES patients.

Method: Sixteen peptide antigen-related IgGs from proteins encoded by schizophrenia-related genes were selected on the basis of several selection criteria from a 2022 genomewide association study. Novel peptide antigen-related IgG levels were measured in drug-naïve FES patients at baseline (n = 155). At the one-year follow-up, 57 patients completed both symptom and autoantibody assessments. Statistical analyses included t tests, Pearson correlation analysis, linear mixed-effects models, and simple slope analysis.

Results: At the one-year follow-up, MOB4 IgG levels were negatively associated with PANSS item P2 scores (r = −0.54, Bonferroni-adjusted P = .029) and item P5 scores (r = −0.65, Bonferroni-adjusted P < .001). Anti-MAD1L1 IgG levels were significantly higher in the remission group compared to the non-remission group (B = −0.14, P = .017), with no notable changes over time. Anti-FURIN IgG levels exhibited divergent trends between the remission and non-remission groups (interaction: B = −0.06, P = .049). Anti-MAPK3 IgG levels were lower in the remission group (B = 0.11, P = .032) but showed a more pronounced rate of increase over time in this group (interaction: B = −0.08, P = .012). Similarly, anti-ACTR1B IgG levels increased significantly in the remission group (interaction: B = −0.07, P = .048).

Discussion & Conclusions: This study underscores the potential of peptide antigen-related IgGs as biomarkers for predicting antipsychotic drug(APD) treatment outcomes in drug-naïve FES patients. Our study observed decreased levels, possibly reflecting APD effects and disease state differences. Changes in antibody levels over one year were correlated with treatment outcomes, highlighting APD-induced immune modulation.