Bipolar Understanding

Courtesy of Eric Robert RussellRecent gene-expression findings may energize the search for a mechanism in bipolar disorder pathology. Chris-tine Konradi and collaborators, from McLean Hospital, Belmont, Mass., and Harvard Medical School, showed that of 43 genes downregulated in brain specimens from subjects with bipolar disorder, 18 encode mitochondrial proteins.1 These results bolster a hypothesis put forth almost four years ago by Tadafumi Kato, currently at the RIKEN Brain Research Institute

A Nicola Schweitzer
Mar 28, 2004
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Courtesy of Eric Robert Russell

Recent gene-expression findings may energize the search for a mechanism in bipolar disorder pathology. Chris-tine Konradi and collaborators, from McLean Hospital, Belmont, Mass., and Harvard Medical School, showed that of 43 genes downregulated in brain specimens from subjects with bipolar disorder, 18 encode mitochondrial proteins.1 These results bolster a hypothesis put forth almost four years ago by Tadafumi Kato, currently at the RIKEN Brain Research Institute in Japan. Mitochondrial dysfunction, he proposed, would explain the abnormal energy metabolism detectable in bipolar brains and could comprehensively account for the patho-physiology of the disorder.2

Konradi, who actually had been seeking schizophrenia-specific gene-expression signatures, says she was stunned by the results in the bipolar disorder specimens she was required to run under brain bank regulations. "More or less everything related to mitochondrial respiration was pretty much downregulated," she says.

Kato says he is glad to hear of Konradi's data. "There are many things to be clarified in the near future," he notes, and he cautions that mitochondrial genes are expressed at unusually high levels, making analyses susceptible to artifacts. Kato adds that Konradi's finding and other emerging studies "suggest that we have to focus on the mitochondria-related molecular cascade in bipolar disorder."

- A. Nicola Schweitzer