For the first time, scientists have shown that genes in the brain’s striatum could be deeply involved in bipolar disorder, according to a new study at the Florida campus of the Scripps Research Institute (TSRI).
The striatum is the part of the brain that coordinates many primary aspects of our behavior, such as motor and action planning, motivation and reward perception. Until now, most research on bipolar disorder has focused on the cortex, the largest part of the brain in humans and the area associated with higher-level thought and action.
The findings also point to several pathways as potential targets for treatment.
“This is the first real study of gene expression in the striatum for bipolar disorder,” said Dr. Ron Davis, chair of the Department of Neuroscience at TSRI, who directed the study. “We now have a snapshot of the genes and proteins expressed in that region.”
For the study, researchers analyzed tissue samples from 35 bipolar and non-bipolar control subjects. The number of genes differentially expressed in tissue samples from the two groups turned out to be surprisingly small — just 14 in all.
However, the researchers also found two modules of interconnected genes that were particularly rich in genetic variations associated with bipolar disorder, suggestive of a causal role in the disorder. One of these two modules was particularly significant, as it seemed to be highly specific to the striatum.
“Our finding of a link between bipolar disorder and the striatum at the molecular level complements studies that implicate the same brain region in bipolar disorder at the anatomical level, including functional imaging studies that show altered activity in the striatum of bipolar subjects during tasks that involve balancing reward and risk,” said TSRI Research Associate Dr. Rodrigo Pacifico, first author of the study.
Studying reactions to risk is important because bipolar patients may act impulsively and engage in high-risk behaviors during episodes of mania.
The researchers also discovered gene changes link ed to the immune system, the body’s inflammatory response, and 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 the future development of diagnostics or treatments,” said Davis.
Bipolar disorder 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.
The new findings are published in the journal Molecular Psychiatry.
Source: Scripps Research Institute