Systematically characterizing dysfunctional long intergenic non-coding RNAs in multiple brain regions of major psychosis

Schizophrenia (SZ) and bipolar disorder (BD) are severe neuropsychiatric disorders with serious impact on patients, together termed “major psychosis”. Recently, long intergenic non-coding RNAs (lincRNAs) were reported to play important roles in mental diseases. However, little was known about their molecular mechanism in pathogenesis of SZ and BD.

Here, researchers from Harbin Medical University performed RNA sequencing on 82 post-mortem brain tissues from three brain regions (orbitofrontal cortex (BA11), anterior cingulate cortex (BA24) and dorsolateral prefrontal cortex (BA9)) of patients with SZ and BD and control subjects, generating over one billion reads. They characterized lincRNA transcriptome in the three brain regions and identified 20 differentially expressed lincRNAs (DELincRNAs) in BA11 for BD, 34 and 1 in BA24 and BA9 for SZ, respectively. The results showed that these DELincRNAs exhibited brain region-specific patterns. Applying weighted gene co-expression network analysis, the researchers revealed that DELincRNAs together with other genes can function as modules to perform different functions in different brain regions, such as immune system development in BA24 and oligodendrocyte differentiation in BA9. Additionally, they found that DNA methylation alteration could partly explain the dysregulation of lincRNAs, some of which could function as enhancers in the pathogenesis of major psychosis.

Differential analyses of lincRNAs in three brain regions for BD and SZ

A. Statistics of differentially expressed lincRNAs and PCGs. B. MA-plots for comparisons between BD or SZ cases and controls in corresponding brain regions. Blue circles, red triangles and violet rectangles denote differentially expressed (DE) PCGs, known and novel lincRNAs, respectively. C. Heatmap representing normalized expression levels of differentially expressed lincRNAs (DELincRNAs) in three brain regions of corresponding disease state. D. Heatmap representing normalized JS scores of the DELincRNAs across 16 tissues. E.–G. GSEA plots for enrichment of brain-specific lincRNAs in all DELincRNAs (E), DELincRNAs in BA11_BD (F), and DELincRNAs in BA24_SZ (G).