Bipolar4LifeSupport

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.

When people with bipolar disorder experience depressive episodes, the reward circuits in their brains show impairments similar to those that affect people diagnosed with major depressive disorder (MDD), scientists reported March 13th in the journal Neuropsychopharmacology. When these circuits are weakened, people’s ability to experience pleasure diminishes.

Most clinical studies exploring how depression affects the brain have focused on people with MDD. Because patients with the two disorders may respond differently to antidepressant medications, it’s important to understand the neurobiology of both groups in order to develop effective treatments.

In patients with bipolar disorder and major depressive disorder, connections between different reward processing regions of the brain were weaker than they were in people without depression. This weakening was greater in patients with more severe depression in both groups.

The scientists did find differences between the two groups of depressed patients. Winning money activated a reward center––the ventral striatum––more strongly in patients with bipolar disorder than it did in those with major depressive disorder. And the strength of certain circuit connections was stronger in patients with bipolar disorder than it was in patients with major depressive disorder. These differences might reflect the two groups’ different risks for manic episodes, during which reward responses appear to be heightened rather than dampened, the scientists say.

Why is it so important to distinguish among brain responses to reward? First, symptoms of depression–– which may be more linked to reward-system dysfunction such as loss of pleasure––tend to be less responsive to standard treatments. “Attenuated reward system response may therefore evolve to be a useful biomarker in drug discovery and clinical trials for mood disorders,” Dr. Satterthwaite says. Second, because many people with bipolar disorder first seek clinical help during depressive episodes, identifying differences between bipolar disorder and major depressive disorder could help ensure patients are accurately diagnosed from the start and receive treatment specifically designed to relieve their symptoms.