Transcriptome sequencing implicates dorsal striatum-specific gene network, immune response and energy metabolism pathways in bipolar disorder
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.
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Prior work has identified differential activation of glial and neural-immune processes in brains of patients with psychiatric disorders.
“Previous work has identified differential activation of glial and neural-immune processes in brain from patients with psychiatric disorders (16, 52, 57, 66–69)”
From Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder (2018) · cites this paper as [68]
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Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder
Gandal, M. J., Zhang, P., Hadjimichael, E., Walker, R. L., Chen, C., Liu, S., Won, H., van Bakel, H., Varghese, M., Wang, Y., et al. (2018) · Science · doi:10.1126/science.aat8127 · Cited by 1,247 · see citing works
- Authors
- Pacifico, R., & Davis, R. L.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Davis, R L
- Venue
- Molecular Psychiatry
- Published
- 2016-06-28
- Volume
- 22
- Issue
- 3
- Pages
- 441-449
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2467259862
- Cited by
- 61
- References
- 69
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 3 · 2023: 4 · 2022: 12 · 2021: 5 · 2020: 7 · 2019: 11 · 2018: 4 · 2017: 2 · 2016: 1
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- bipolar disorder, dorsal striatum, immune response genes, inflammation, oxidative phosphorylation, energy metabolism, medium spiny neurons, gene co-expression network, single nucleotide polymorphisms, NLRC5, S100A12, FCGBP
- MeSH terms
- Adult, Aged, Aged, 80 and over, Autopsy, Bipolar Disorder, Brain, Central Nervous System, Corpus Striatum, Energy Metabolism, Female, Humans, Immunity, Active, Male, Middle Aged, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Gene Expression Profiling, Gene Regulatory Networks, Genome-Wide Association Study, Transcriptome
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