Transcriptome profiling of the dorsomedial prefrontal cortex in suicide victims

Abstract

The default mode network (DMN) plays an outstanding role in psychiatric disorders. Still, gene expressional changes in its major component, the dorsomedial prefrontal cortex (DMPFC), have not been characterized. We used RNA-sequencing in postmortem DMPFC samples to investigate suicide victims compared to control subjects. Most of the data variance (79%) was associated with expression changes between suicide and control samples. 1400 genes differed using log2FC > ± 1 and adjusted p-value < 0.05 criteria between groups. Genes associated with depressive disorder, schizophrenia and impaired cognition were strongly overexpressed in top differentially expressed genes. Gene set enrichment and protein-protein interaction network analysis revealed that pathways related to cytokine receptor signaling were enriched in downregulated while glutamatergic synaptic signaling in upregulated genes in suicide individuals. A validated differentially expressed gene, which is known to be associated with mGluR5, was the N-terminal EF-hand calcium-binding proteins 2 (NECAB2). In situ hybridization histochemistry and immunohistochemistry proved that NECAB2 is expressed in 2 different types of inhibitory neurons located in layers II-IV and VI, respectively. Our results imply extensive gene expressional alterations in the DMPFC related to suicidal behavior. Some of these genes may contribute to the altered mental state and behavior of suicide victims.