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Increased gray matter volume in lithium-treated bipolar disorder patients.

Lithium's neurotrophic effects have been reported in several in vitro and ex vivo studies. Preliminary human studies with magnetic resonance imaging (MRI) and spectroscopy have recently provided evidence of lithium-induced increases in gray matter volumes and N-acetyl-aspartate levels. In order to further examine the hypothesis that lithium treatment would relate to detectable increases in gray matter brain content, we blindly measured gray and white matter volumes in MRI images of 12 untreated and 17 lithium-treated bipolar patients and 46 healthy controls. Using multivariate analysis of covariance with age and gender as covariates, we found that total gray matter volumes were significantly increased in lithium-treated (747.9 +/- 69.8 cm(3)) compared with untreated patients (639.2 +/- 91.2 cm(3); F = 10.6; d.f. = 1, 25; P = 0.003) and healthy individuals (675.8 +/- 61.8 cm(3); F = 17.4; d.f. = 1, 59; P < 0.001), suggesting in vivo effects of lithium on gray matter, which could possibly reflect lithium's neurotrophic effects.

Pubmed ID: 12165422


  • Sassi RB
  • Nicoletti M
  • Brambilla P
  • Mallinger AG
  • Frank E
  • Kupfer DJ
  • Keshavan MS
  • Soares JC


Neuroscience letters

Publication Data

August 30, 2002

Associated Grants

  • Agency: NIMH NIH HHS, Id: MH01736
  • Agency: NIMH NIH HHS, Id: MH29618
  • Agency: NIMH NIH HHS, Id: MH30915

Mesh Terms

  • Analysis of Variance
  • Bipolar Disorder
  • Brain
  • Chi-Square Distribution
  • Cross-Sectional Studies
  • Female
  • Humans
  • Lithium Chloride
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Statistics, Nonparametric