Science + Technology

Lithium Builds Gray Matter in Bipolar Brains, UCLA Study Shows

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Neuroscientistsat UCLA have shown that lithium, long the standard treatment for bipolardisorder, increases the amount of gray matter in the brains of patients withthe illness.

Theresearch is featured in the July issue of the journal Biological Psychiatry andis currently available online.

CarrieBearden, a clinical neuropsychologist and assistant professor of psychiatry atUCLA, and Paul Thompson, associate professor of neurology at the UCLALaboratory of NeuroImaging, used a novel method of three-dimensional magneticresonance imaging (MRI) to map the entire surface of the brain in peoplediagnosed with bipolar disorder.

Whenthe researchers compared the brains of bipolar patients on lithium with thoseof people without the disorder and those of bipolar patients not on lithium,they found that the volume of gray matter in the brains of those on lithium wasas much as 15 percent higher in areas that are critical for attention andcontrolling emotions.

Theneurobiological underpinnings of bipolar disorder — an illness marked by aroller coaster of emotions between mania and depression — are not wellunderstood. Nor is it understood how lithium works in controlling these severemood swings, even though it has been the standard treatment for some 50 years.These new findings suggest that lithium may work by increasing the amount ofgray matter in particular brain areas, which in turn suggests that existinggray matter in these regions of bipolar brains may be underused ordysfunctional.

Thisis the first time researchers were able to look at specific regions of thebrain that may be affected by lithium treatment in living human subjects, saidBearden.

"Weused a novel method for brain imaging analysis that is exquisitely sensitive tosubtle differences in brain structure," she said. "This type of imaging has notbeen used before to study bipolar patients. We also revealed how commonly usedmedications affect the bipolar brain."

Althoughother studies have measured increases in the overall volume of the brain,Bearden said, this imaging method allowed the researchers to see exactly whichbrain regions were affected by lithium.

"Bipolarpatients who were taking lithium had a striking increase in gray matter in thecingulate and paralimbic regions of the brain," she said. "These regionsregulate attention, motivation and emotion, which are profoundly affected inbipolar illness."

While conventional MRI studies have measured brain volume intotal, this new image analysis allows researchers to examine differences incortical anatomy at a much greater spatial resolution.

In this study, Beardenand colleagues at UCLA used computer analysis to analyze brain scans collected by collaborators at theUniversity of Pittsburgh in order to determine whether bipolar patients showedchanges in brain tissue and, if so, whether those changes were influenced bylithium treatment. Specifically, they employed high-resolution MRI and corticalpattern-matching methods to map gray matter differences in 28 adults withbipolar disorder — 70 percent of whom were lithium-treated — and 28 healthycontrol subjects. Detailed spatial analyses of gray matter distribution wereconducted by measuring local volumes of gray matter at thousands of locationsin the brain.

Whilethe brains of lithium-treated bipolar patients did not differ from those of thecontrol subjects in total white-matter volume, their overall gray-matter volumewas significantly higher, sometimes by as much as 15 percent.

Unfortunately,said Bearden, there is no evidence that the increase in gray matter persists iflithium treatment is discontinued. "But it does suggest that lithium can havedramatic effects on gray matter in the brain," she said. "This may be animportant clue as to how and why it works."

Otherauthors in the study included Manish Dalwani, Kiralee M. Hayashi, Agatha D.Lee, Mark Nicoletti, Michael Trakhtenbroit, David C. Glahn, Paolo Brambilla,Roberto B. Sassi, Alan G. Mallinger, Ellen Frank, David J. Kupfer, and Jair C.Soares.

Graphics from the study are available online at: www.loni.ucla.edu/~khayashi/Texas/BIPOLAR/newCOVER_8x10_bipolar.tif.

TheUCLA Department of Neurology encompasses more than a dozen research, clinicaland teaching programs. These programs cover brain mapping and neuroimaging,movement disorders, Alzheimer's disease, multiple sclerosis, neurogenetics,nerve and muscle disorders, epilepsy, neuro-oncology, neurotology,neuropsychology, headaches and migraines, neurorehabilitation, andneurovascular disorders. The department ranked No. 1 among its peers nationwide in National Institutes of Healthfunding in 2005. For more information, visit http://neurology.medsch.ucla.edu.

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