Identification of shared pathophysiological molecules of major psychiatric disorders: A comprehensive analysis of serum immune complex antigens before and after electroconvulsive therapy

Abstract

Recent studies indicate common inflammatory findings have been identified in peripheral blood in patients with major psychiatric disorders, including schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). Electroconvulsive therapy (ECT) frequently improves both severe symptoms and inflammatory markers in these conditions. However, the shared inflammatory mechanisms underlying these disorders, and thus, reliable biomarkers remain unclear. We hypothesized that the activation of immune complexes (ICs) contributes to inflammatory pathogenesis of these disorders. Using immune complexome analysis, we examined antigens forming ICs (IC-antigens) in the serum of patients with SCZ, BD, and MDD (n = 60) before and after ECT. Our analysis showed that although the overall quantity of ICs did not change before and after ECT, four proteins significantly decreased following ECT. These proteins were DENN domain-containing protein 1C (DENND1C), double-stranded RNA-specific editase 1 (ADARB1), perilipin-4, and coagulation factor XI, which were all consistently detected as IC-antigens across patient groups. Notably, DENND1C, ADARB1, and perilipin-4 were specific to psychiatric patients and absent in healthy controls. The abundance of these IC-antigens significantly correlated with psychiatric symptom scores, with DENND1C showing a particularly strong correlation with total symptom scores across all three disorders. These findings suggest that DENND1C may contribute to the shared pathophysiology of SCZ, BD, and MDD through antigenization or IC formation. This highlights its potential as a biomarker for ECT treatment availability and diagnostic/treatment efficacy monitoring.