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  • Brain maps uncover lithium’s effect on bipolar disorder

May 2007
Ashley L. Brenon

For 50 years scientists have recognized the positive outward effects of lithium treatment on bipolar disorder, but, until recently, they could not measure precisely the effects of the drug on the brain itself.

With advancements in 3-D computational image analysis, scientists can view the entire brain at higher spatial resolution, surpassing the accuracy of region-specific volumetric studies used in the past to study the effects of lithium on patients with bipolar disorder.

In a study scheduled to appear in the July issue of Biological Psychiatry, Carrie E. Bearden and her colleagues from the University of California, Los Angeles, and from the University of Texas at San Antonio used 3-D MRI and cortical pattern matching to measure gray matter density in the brains of 28 healthy control subjects and 28 patients with bipolar disorder, 71 percent of whom were treated with lithium.

Brain maps indicate the statistical significance of gray matter density increases in bipolar patients treated with lithium (Li+) vs. controls (a). In contrast, the gray matter density in bipolar patients who were not taking lithium (Li–) did not differ significantly from that of controls in any cortical region (b).

Magnetic resonance images were acquired with a 1.5-T GE Signa imaging system at the University of Pittsburgh and processed with a series of manual and automated procedures to extract and render each individual’s cortical surface. The scientists used cortical pattern matching methods to create deformation maps that corresponded to the anatomical features of the cortex.

By measuring gray matter concentration at each of thousands of cortical surface points, the scientists created gray matter maps for each subject, which were averaged across groups to localize the disease’s effects.

Examination of cortical surface maps indicated that gray matter density was greater by 10 percent or more in the bipolar group in brain regions responsible for attention, motivation and emotion, which are affected in patients with bipolar disorder.

Because the majority of the patients in the bipolar group were taking lithium, the researchers hypothesized that increased gray matter in specific regions may result from the medication. They subdivided the bipolar group into patients taking lithium and those who were not. In all cases, the gray matter increases observed in the bipolar group were entirely attributable to patients treated with lithium.

Although further studies are necessary to investigate lithium’s functional mechanisms, increasing evidence indicates that the drug activates proteins that prevent normal gray matter cell death. Because lithium takes at least seven days to affect cultured cells, and its effects are not immediately reversed upon discontinuation, the researchers believe that lithium initiates a complex biological response.

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