Gene expressional changes in the dorsomedial prefrontal cortex of suicide victims

Recent studies revealed that human cortical networks, especially the Default-mode Network (DMN), have an outstanding role in psychiatric disorders. However, expressional alterations related to depression and suicidal behavior have not been reported in the dorsomedial prefrontal cortex (DMPFC), one of the a major and functionally significant component of the DMN. We used RNA sequencing in microdissected DMPFC samples to investigate the molecular changes in suicide victims without any medication for chronic depression as compared to control subjects without identified psychiatric disorders. Between the 2 groups more than 1000 genes differed, and RT-PCR validated 15 of them. In order to identify patterns in the transcriptome data, gene set enrichment analysis was used and identified functional pathways enriched in up- and down-regulated genes. The glutamatergic synapse, growth factor receptor signaling and cytokine receptor pathways were over-represented in suicide victims suggesting that these processes are involved in suicidal behavior. One of the validated differentially expressed genes was the neuronal Ca(2+)-binding protein 2 (NECAB2). Since this gene may have great importance in modulating neuronal functions, and previously not fully characterized for its role in depression and suicide, we aimed to further characterize them by performing in situ hybridization and immunohistochemistry to describe its distribution in different cortical layers of the DMPFC. Together with a comparison to cell type-specific gene expressional data of the Allan Brain Atlas suggest that NECAB2 is located mainly in layer II-IV and VI inhibitory neurons. 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.