Greater Cortical Gray Matter Density in Lithium-Treated Patients with Bipolar Disorder


      The neurobiological underpinnings of bipolar disorder are not well understood. Previous neuroimaging findings have been inconsistent; however, new methods for three-dimensional (3-D) computational image analysis may better characterize neuroanatomic changes than standard volumetric measures.


      We used high-resolution magnetic resonance imaging and cortical pattern matching methods to map gray matter differences in 28 adults with bipolar disorder, 70% of whom were lithium-treated (mean age = 36.1 ± 10.5; 13 female subject), and 28 healthy control subjects (mean age = 35.9 ± 8.5; 11 female subjects). Detailed spatial analyses of gray matter density (GMD) were conducted by measuring local proportions of gray matter at thousands of homologous cortical locations.


      Gray matter density was significantly greater in bipolar patients relative to control subjects in diffuse cortical regions. Greatest differences were found in bilateral cingulate and paralimbic cortices, brain regions critical for attentional, motivational, and emotional modulation. Secondary region of interest (ROI) analyses indicated significantly greater GMD in the right anterior cingulate among lithium-treated bipolar patients (n = 20) relative to those not taking lithium (n = 8).


      These brain maps are consistent with previous voxel-based morphometry reports of greater GMD in portions of the anterior limbic network in bipolar patients and suggest neurotrophic effects of lithium as a possible etiology of these neuroanatomic differences.

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      • Lithium and Increased Cortical Gray Matter—More Tissue or More Water?
        Biological PsychiatryVol. 63Issue 3
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          I read Bearden and colleagues’ “Greater Cortical Gray Matter Density in Lithium-Treated Patients with Bipolar Disorder” with great interest. I was hoping to learn that they had performed analyses to determine whether an increase in brain tissue water could have contributed to their finding increased cortical gray matter density in lithium-treated patients. However, like other investigators finding increased cortical thickness in bipolar subjects taking lithium (1,2), Bearden and colleagues did not report any data measuring gray matter water content.
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