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August 27, 2005

Bipolar Disorder Has Link to Energy Deficiency

Belmont, MA - Is bipolar disorder related to an energy deficiency in the brain? Can researchers find ways to stabilize this deficiency in order to help those suffering from the illness? These questions and other issues are addressed in a revolutionary new study (abstract) from McLean Hospital published in the March 1, 2004 Archives of General Psychiatry.

The study reveals that the mitochondria, cell organelles in the brain important for energy conversion, might not function as effectively in the brains of individuals with bipolar disorder as they do in the brains of controls or those with schizophrenia. The discovery of this dysfunction could have significant implications for the diagnosis and treatment of bipolar disorder, a psychiatric illness characterized by recurrent episodes of depression and mania, which affects nearly 2.3 million adult Americans.

According to the study's lead investigator, Christine Konradi, PhD, mitochondria are the body's "power plants," helping to convert the energy we get from food (glucose) into a form our bodies can use. Much like the way an oil refinery processes crude oil, mitochondria take the raw materials from our nutrients and "refine" them so that our cells can use the energy. However, in individuals with bipolar disorder, something in this energy conversion appears to go awry.

When Konradi, director of McLean Hospital's Neuroplasticity Laboratory, and her colleagues compared gene levels in the brains of 27 subjects with bipolar disorder to those with schizophrenia and to controls, they discovered the genes that make the proteins involved in energy transfer were significantly "down-regulated" in the brains of subjects with bipolar disorder.

"The reduction of these genes indicates that either there are not enough of these 'power plants' in the cells or that these power plants are not efficient," Konradi said. "Our study therefore suggests a causal relationship between bipolar disorder and decreased energy transfer. If this is the case, it could completely refocus our approach to the treatment of bipolar disorder."

Konradi's research concentrated primarily on the hippocampus, one of the brain areas indicated in bipolar disorder. Energy deficits were also evident in the brain's cortex.

While bipolar disorder affects nearly 2.3 million adult Americans, little is known about the disease's etiology or function. Studies indicate a hereditary component, but no gene or gene expression has been linked conclusively to the illness. Because it indicates decreased levels of mitochrondrial genes, the McLean study provides further evidence that the abnormal expression of genes involved in energy metabolism is closely related to bipolar disorder.

"Our hope is that this research will attract the pharmaceutical industry to explore new treatment approaches," Konradi said. "While there are many diseases related to mitochondrial dysfunction, they are so rare that there is little incentive to fund research. But bipolar disorder affects a huge population. If drug companies can support efforts to stabilize energy conversion in these individuals, we could potentially help millions of people."

McLean Hospital maintains the largest research program of any private psychiatric hospital in the nation. It is the largest psychiatric clinical care, research and teaching facility of Harvard Medical School, an affiliate of Massachusetts General Hospital and a member of Partners HealthCare.

Cindy Lepore
Source: McLean Hospital, a Harvard Medical School affiliate.


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