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

Carrie E. Bearden, Paul M. Thompson, 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, Jair C. Soares

Research output: Contribution to journalArticlepeer-review

212 Scopus citations


Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)7-16
Number of pages10
JournalBiological psychiatry
Issue number1
StatePublished - Jul 1 2007
Externally publishedYes


  • Bipolar disorder
  • cortical pattern matching
  • lithium
  • magnetic resonance imaging
  • mood disorders
  • neuroprotection

ASJC Scopus subject areas

  • Biological Psychiatry


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