PHILADELPHIA—Findings from a recent study by researchers at Stanford University School of Medicine in California showed a decrease in left frontal lobe gray matter in male patients with bipolar I disorder as compared with healthy controls. According to Nathan Dieckmann, a staff researcher at the Stanford Bipolar Disorders Clinic and a member of the Department of Psychiatry and Behavioral Sciences, “These findings may be particularly robust as they emerged in this sample, while differences in ventricular and cerebellar volumes, which were expected in view of prior studies, were not significant.” Mr. Dieckmann and his colleagues reported their findings at the 2002 Annual Meeting of the American Psychiatric Association.

NEUROBIOLOGIC ABNORMALITIES

Several structural and functional brain abnormalities—subgenual prefrontal volume, increased sulcal prominence, increased subcortical hyperintensities, lateral and third ventricle enlargement, cerebellar atrophy, and amygdalar and temporal lobe changes—have been associated with bipolar disorder, the researchers noted. Additionally, decreased prefrontal cerebral blood flow and metabolism, and decreased dorsolateral prefrontal N-acetyl aspartate (NAA) levels, have been observed.

Using magnetic resonance imaging and magnetic resonance spectroscopy, the investigators assessed brain volumes and chemistry in 36 patients with bipolar disorder (mean age, 36) and 21 healthy controls (mean age, 38). Among the patients with bipolar disorder, 18 (11 men) were diagnosed as having bipolar I disorder.

Analysis of the imaging data revealed that male patients with bipolar I disorder had a 10% decrease in left frontal lobe gray matter as compared with male controls. The researchers also reported that left dorsolateral prefrontal NAA tended to be lower in bipolar patients than in controls. This decrease correlated significantly with the decrease in left frontal lobe gray matter in men with bipolar I disorder, an indication that the number of neurons in the left frontal lobe is decreased, Mr. Dieckmann said.

A LOOK AHEAD

The results offered support for the relationship between structural and functional frontal lobe abnormalities in bipolar disorder, according to Mr. Dieckmann. The apparent sex-related trend is perhaps indicative of a “neuroprotective effect” in females, “perhaps due to hormonal output,” he postulated. Further research might examine whether the perceived protective effect is sensitive to age or menopausal factors in women.

Other areas of research to be pursued include determining whether bipolar I or bipolar II is associated with worse structural abnormalities and determining whether there are response predictors based on the degree of structural abnormalities.

—C. Justin Romano

Suggested Reading
Winsberg ME, Sachs N, Tate DL, et al. Decreased dorsolateral prefrontal N-acetyl aspartate in bipolar disorder. Biol Psychiatry. 2000;47:475-481.

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