Peripheral Blood RNA-seq analysis in Bipolar and Schizophrenia Spectrum Disorders: Modest Influence of Antipsychotic Treatment

Abstract

Introduction: Bipolar disorder (BP) and schizophrenia spectrum disorders (SSD) are chronic mental health conditions that share genetic risks. Despite extensive research, the biological mechanisms underlying these disorders are still not fully understood. Methods: In this study, we analyzed peripheral blood RNA-seq data from 64 patients with BP and SSD, both on and off antipsychotic treatment, and 92 healthy controls. We conducted differential gene expression analyses, pathway enrichment analyses, weighted gene co-expression network analysis (WGCNA), and clinical trait association analyses. Results: Patients showed distinct blood transcriptomic profiles compared to controls, with a core set of 1,278 differentially expressed genes shared between individuals with mental illness, both on and off antipsychotics. These common DEGs were enriched in immune processes, metabolic pathways, and cellular homeostasis functions. WGCNA identified a co-expression module that was strongly associated with mental illness status and not with metabolic traits. We also observed a significant group effect for total cholesterol, LDL cholesterol, systolic blood pressure, and diastolic blood pressure when comparing metabolic clinical features among MD, MD+APs, and HC. Conclusion: This transcriptomic study of BP and SSD in a Qatar-based cohort highlights dysregulated immune and metabolic pathways.