Immunophenotyping schizophrenia subtypes stratified by antipsychotic response

• DOI: 10.1016/j.bbi.2024.10.019
• Publication Date: 2024-10-14T06:24:30Z
• Authors: Yanhui Li; Jocelyn Wen Xin Ong; Yuen Mei See; Jie Yin Yee; Charmaine Tang; Shushan Zheng; Boon Tat Ng; Bernett Teck Kwon...; Olaf Rotzschke; Anand Kumar Andia...; Jimmy Lee
• Keywords: Immunophenotyping

Immune dysfunction has been proposed to play a role in the pathophysiology behind development and persistence of psychosis. Current immunophenotyping studies are limited by small sample sizes number immune markers investigated. Pharmacological subtypes schizophrenia based on antipsychotic response have proposed, but few investigated immunophenotypes treatment-resistant schizophrenia. In this study, we perform comprehensive 196 subjects comprising 147 patients stratified (49 antipsychotic-responsive, 70 clozapine-responsive, 28 clozapine-resistant) 49 healthy controls. We aim identify significant cell populations associated with increasing treatment resistance, as potential modulators underlying psychosis and/or response. Patients were recruited assessed Clinical Global Impression - Schizophrenia (CGI-SCH). Treatment was defined rating three (mild severity) or less CGI-SCH positive symptom item after at least 8 weeks adequate clozapine treatment. Peripheral blood mononuclear cells collected flow cytometry performed 66 populations. Differences population proportions compared between cases controls, across all 4 groups, post-hoc pairwise comparisons. Mucosal-associated invariant T (MAIT) (specifically CD8 + DN double-negative subsets), total, exhausted memory cells, VD1 ϒδ plasmablasts, IgG B conventional dendritic 2 (cDC2) among top downregulated observed increased downregulation resistance. Conversely, naïve CD4 CD4/CD8 ratio CCR5 CCR2 HLA DR Myeloid found be upregulated upregulation show immunophenotypic differences consistent trend varying degrees also examined not previously reported Future may explore identified biomarkers clarify relationship immunological changes pharmacological