In Bipolar Disorder, a Chemical Signal of Abnormal Metabolism

It has long been a puzzle what exactly causes the intense highs and lows of bipolar disorder, an illness that pushes people back and forth from periods of intense energy and excitement to periods of deep sadness and hopelessness. But evidence is stacking up that this disorder may involve abnormalities in metabolism, the wide range of chemical reactions that help sustain the body and brain.

Now, a research team has found previously unobserved structural differences in the brains of people with bipolar disorder that may reflect disruptions to metabolism, suggesting those processes may broadly contribute to the illness. Their study was published January 6th inMolecular Psychiatry.

Led by John A. Wemmie, M.D., Ph.D., of the University of Iowa––a 2004 and 2007 NARSAD Young Investigator (YI) grantee and 2013 NARSAD Independent Investigator (II) grantee––the team looked at levels in the brain of a signal called T1ρ. This signal has proven sensitive to different brain abnormalities linked to bipolar disorder, including unusual concentrations of metabolites, the chemical reactants and byproducts of the body’s metabolic systems. Using a unique imaging method not typically applied to psychiatric conditions, the team found that T1ρ levels were higher in certain parts of the brain for people with bipolar disorder compared to those who do not have the illness. In particular, T1ρ was high in white matter portions of the cerebral cortex, which contains cells that shape communication within the brain, and also in the cerebellum, which controls motor functions.

Since T1ρ is sensitive to a number of brain features linked with bipolar disorder, the team tested whether the high levels of this signal stemmed from other factors besides metabolism. Their analyses suggested that those other factors did not affect the findings, pointing to irregular metabolism as the root of the high T1ρ levels. This possibility likely will be more closely studied in the future using other imaging techniques.

Importantly, this study also found that medication affected T1ρ levels. Among people in the study with bipolar disorder, those who were taking the mood regulator lithium had normal T1ρ levels in the cerebellum, compared to elevated levels found in those not taking the drug. Lithium, then, may help specifically to reverse abnormalities in the cerebellum among people with bipolar disorder.

Because this study looked at people with bipolar disorder who were experiencing neither an intense high nor intense low period, it’s not yet known what T1ρ levels look like during those states. It is also an open question whether the observed cerebral white matter and cerebellum abnormalities appear in other conditions that affect mood, including schizophrenia anddepression.

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