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Bipolar disorder link to striatum brain region

Bipolar disorder is one of the most-studied neurological disorders. The Greeks noticed symptoms of the disease in the first century. Science has now recognized a possible brain region for its source - the striatum.


Bipolar disorder (BD) is a mental illness that affects about 2.6 percent of the U.S. adult population — some 5.7 million Americans — with a sizable majority of these cases classified as severe. The disease runs in families, and more than two-thirds of people with bipolar disorder have at least one close relative with the illness or with unipolar major depression, according to the National Institute of Mental Health.

Childhood bipolar disorder, or pediatric bipolar disorder, is a form of bipolar disorder that can occur in children. Although its existence is still a matter of academic debate and disagreement, there is a growing body of evidence suggesting bipolar disorder can exist in children.

In this new research in adults, tissue samples from 35 bipolar and non-bipolar control subjects were analyzed. The number of genes differentially expressed turned out surprisingly small — just 14 in all tissue samples from both groups.

Most modern studies of BD concentrate on the cortex of the brain, the largest part of our brain associated with higher-level thought and action. But for the first time, scientists from the Florida campus of The Scripps Research Institute (TSRI) show that genes within the striatum could be involved in Bipolar disorder (BD). The striatum coordinates many aspects of behavior such as motivation, perception of reward and how we plan responses.

The striatum is divided into dorsal (top) and ventral (bottom) regions, with a small degree of overlap between the two. The ventral striatum primarily defines the rewarding stimuli that reinforces motivation. While the dorsal striatum primarily defines motor response to stimuli, such as: attention control, inhibition control, working memory, flexibility in thinking, reasoning, problem solving and planning. Or simply put, the dorsal striatum coordinates motor stimulus-response to learning. 


"This is the first real study of gene expression in the striatum for bipolar disorder. We now have a snapshot of genes and proteins expressed in that region."

Ron Davis PhD, Chair, Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL, USA and leader of the study


The study is published in the journal Molecular Psychiatry.

Analysis reveals two groups of interconnected genes enriched with gene markers characteristic of dorsal striatum medium spiny neurons are expressed. One of these two particularly stood out, as it seemed highly specific to the striatum.

These findings not only draw a link between BD etiology at the gene level and in specific brain regions, but highlight striatal signaling pathways as potential targets for treatments to manage BD.


"Our finding of a link between bipolar disorder and striatum at the molecular level, complements studies implicating the same brain region in bipolar disorder at the anatomical level.

"Functional imaging studies show altered activity in the striatum of bipolar subjects in tasks involving balancing reward and risk."


Rodrigo Pacifico PhD, Research Associate, Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL, USA and first author of the study.


Analyzing reactions to risk is important as bipolar patients can act impulsively, engaging in high-risk activities during periods of mania.

Pathway analysis also found changes in genes linked to the immune system (the body's inflammatory response) and a cells' energy metabolism.


"We don't know if these changes are a cause of the disease or the result of it. But they provide additional gene markers in bipolar disorder that could potentially lead to development of diagnostics or treatments."

Ron Davis PhD


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.

The study, "Transcriptome Sequencing Implicates Dorsal Striatum-Specific Gene Network, Immune Response and Energy Metabolism Pathways in Bipolar Disorder," was supported by funding from the State of Florida.

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Jul 12, 2016   Fetal Timeline   Maternal Timeline   News   News Archive   



The stiatum - ORANGE. This study is the first to identify the striatum
as part of the brain coordinating many aspects of Bipolar Disorder.
Image Credit: Okinawa Institute of Science and Technology Graduate University, Japan OIST


 


 

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