DESCRIPTION:

Bipolar disorder a is highly heritable mental illness that has definable behavioral traits associated with it. Dorsal striatum is linked to impulsivity and risk-taking behavior. This brain structure was collected from human (postmortem) brain samples and was mapped using RNA sequencing, specifically DESeq2. 1468 genes were identified as differentially expressed at nominal significance between the BD striatal group vs. the control group.

LABEL:

DiffExp_Stri_BDxC

SCORE TYPE:

Q-Value

DATE ADDED:

2020-04-02

DATE UPDATED:

2020-12-02

SPECIES:

AUTHORS:

R Pacifico, R L Davis

TITLE:

Transcriptome sequencing implicates dorsal striatum-specific gene network, immune response and energy metabolism pathways in bipolar disorder.

JOURNAL:

Molecular psychiatry 03 2017, Vol 22, pp. 441-449

ABSTRACT:

Bipolar disorder (BD) is a highly heritable and heterogeneous mental illness whose manifestations often include impulsive and risk-taking behavior. This particular phenotype suggests that abnormal striatal function could be involved in BD etiology, yet most transcriptomic studies of this disorder have concentrated on cortical brain regions. We believe we report the first transcriptome sequencing of the postmortem human dorsal striatum comparing bipolar (18) and control (17) subjects. Fourteen genes were detected as differentially expressed at a 5% false discovery rate, including a few immune response genes such as NLRC5, S100A12, LILRA4 and FCGBP, as well as an assortment of non-protein coding genes. Functional pathway analysis found an enrichment of upregulated genes across many immune/inflammation pathways and an enrichment of downregulated genes among oxidative phosphorylation pathways. Co-expression network analysis revealed 20 modules of highly interconnected genes; two of the modules were significantly enriched for BD susceptibility single-nucleotide polymorphisms deriving from a large genome-wide association study data set. Remarkably, the module with the highest genetic association signal for BD, which contained many genes from signaling pathways, was also enriched in markers characteristic of gene expression in dorsal striatum medium spiny neurons-unlike most other modules, which showed no such regional and neuronal specificity. These findings draw a link between BD etiology at the gene level and a specific brain region, and highlight striatal signaling pathways as potential targets for the development of novel treatments to manage BD. PUBMED: 27350034
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