Analysis of the immune microenvironment in multiple brain regions in bipolar disorder

Objective : In this study, immune microenvironment changes in the anterior cingulate cortex (AnCg), dorsolateral prefrontal cortex (DLPFC), and nucleus accumbens (nAcc) of BD patients will be characterized. Additionally, the relationship between BD and the immune system at the levels of immune cells, genes, and pathways will be systematically explored, and immunopathological features and their possible roles in disease mechanisms will be identified. Methods : Based on 141 samples from the Gene Expression Omnibus (GEO) database (GSE80655), including 24 BD patients and 24 controls, the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm was used to analyze immune cell proportions in the AnCg, DLPFC, and nAcc regions. Differentially expressed genes (DEGs) and immune-related DEGs were identified using the edgeR package. Spearman correlation analysis was performed to assess correlations between immune cells and between immune cells and genes. A protein-protein interaction (PPI) network was constructed to identify hub genes, and Gene Set Variation Analysis (GSVA) was used to evaluate differences in immune-related pathways. Results : In BD, the nAcc revealed higher levels of T cells CD8 (false discovery rate (FDR) < 0.05). The immune-related hub genes chitinase 3 like 1 ( CHI3L1 ), interleukin 1 receptor like 1 ( IL1RL1 ), and interleukin 4 receptor ( IL4R ) were among the genes that showed the greatest differential expression in the AnCg. Increased immune cell correlations in BD, especially in the AnCg, suggested that innate and adaptive immunity interact. The AnCg showed a significant change in chemokine signaling pathways (FDR < 0.05). Conclusions : Immune dysregulation varies by brain region in BD patients, with the most noticeable changes seen in the AnCg. These include chemokine signaling pathways and immune-related genes like CHI3L1 , IL1RL1 , and IL4R which are significantly dysregulated. These findings suggest that different immune regulatory mechanisms may play a role in the pathogenesis of disease in different parts of the brain.