Quantitative, High-Resolution T1 Rho MRI Mapping Scan Reveals Brain Differences in Bipolar Disorder

In particular, the study revealed differences in the white matter of patients’ brains and in the cerebellum, an area of the brain not previously linked with the disorder.

Interestingly, the cerebellar differences were not present in patients taking lithium, the most typically used treatment for bipolar disorder. “This imaging technique appears to be sensitive to things that just have not been imaged effectively before. So it’s really providing a new picture and new insight into the composition and function of the brain [in bipolar disease],” said John Wemmie, MD, PhD, University of Iowa (UI; Iowa City, USA) professor of psychiatry, and senior study author. The findings were published January 6, 2015, in the journal Molecular Psychiatry.

Bipolar disorder affects about 1% of the population. In spite of being comparatively common, scientists do not have a good determination of what causes this psychiatric condition, which is characterized by sudden mood shifts from normal to depressed or to an abnormally elevated or “manic” mood state. The study examined 15 patients with bipolar disorder and 25 control subjects matched for age and gender. The bipolar patients were all in normal (euthymic) mood state during the study.

The UI researchers imaged the study participants’ brains using an MRI strategy known as quantitative high-resolution T1 rho mapping, which is sensitive to specific byproducts of cell metabolism, including levels of glucose and acidity in the brain. Compared to the brains of people without bipolar disorder, the investigators discovered that the MRI signal was raised in the cerebral white matter and the cerebellar region of patients affected by bipolar disorder. The elevated signal may be due to either a reduction in pH or a reduction in glucose concentration—both factors affected by cell metabolism.

Previous research has suggested that abnormal cell metabolism may play a role in bipolar disorder. However, investigating metabolic abnormalities in the brain has been encumbered by the lack of good imaging strategies. Available techniques are slow, low-resolution, and require researchers to identify the region of interest at the beginning of the study. By contrast, the new imaging approach can rapidly acquire a high-resolution image of the whole brain. The study is the first time this MRI technique has been used to study a psychiatric disease.

One reason researchers did not recognize that the cerebellum might be important in bipolar disorder, is because no one chose to search there, according to Casey Johnson, PhD, a UI postdoctoral researcher, and first author on the study. “Our study was essentially exploratory. We didn’t know what we would find. Most of the bipolar disorder research has found differences in the frontal region of the brain. We found focal differences in the cerebellum, which is a region that hasn't really been highlighted in the bipolar literature before.”

Spurred on by the finding, Drs. Johnson and Wemmie conducted a widespread search of the scientific literature on bipolar disorder and began to locate bits of evidence that suggested that the cerebellum may function abnormally in bipolar disorder and that lithium might potentially target the cerebellum and alter glucose levels in this brain region. “Our paper, with this new technique, starts to bring all these pieces of evidence together for the first time,” Dr. Johnson noted.

Dr. Wemmie hopes that the new clues provided by the T1 rho imaging might help to better understand the abnormalities that underlie bipolar disease and lead to enhanced ways to diagnose and treat this problem. Even though lithium can be an effective mood stabilizer for people with bipolar disorder, it causes many disagreeable side effects for patients.

“If lithium’s effect on the cerebellum is the key to its effectiveness as a mood stabilizer, then a more targeted treatment that causes the same change in the cerebellum without affecting other systems might be a better treatment for patients with bipolar disorder,” Dr. Wemmie said.

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