Lithium and valproic acid treatment effects on brain chemistry in bipolar disorder

Biol Psychiatry. 2004 Sep 1;56(5):340-8. doi: 10.1016/j.biopsych.2004.06.012.

Abstract

Background: Prior work reported elevated gray matter (GM) lactate and Glx (glutamate + glutamine + GABA) concentrations in unmedicated patients with bipolar disorder (BP) compared with healthy controls (HC). This study examined whether lithium (Li) and valproic acid (VPA) treatment modulated these chemicals.

Methods: A subset of previously reported BP patients were treated with Li (n = 12, 3.6 +/- 1.9 months) or VPA (n = 9, 1.4 +/- 1.7 months) and compared untreated HC subjects (n = 12, 2.9 +/- 2.4 months) using proton echo-planar spectroscopic imaging. Regression analyses (voxel gray/white composition by chemistry) were performed at each time point, and change scores computed. Metabolite relaxation and regions of interest (ROI) were also examined.

Results: Across treatment, Li-treated BP subjects demonstrated GM Glx decreases (Li-HC, p =.08; Li-VPA p =.04) and GM myo-inositol increases (Li-HC p =.07; Li-VPA p =.12). Other measures were not significant. Serum Li levels were positively correlated with Glx decreases at the trend level.

Conclusions: Li treatment of BP was associated with specific GM Glx decreases and myo-inositol increases. Findings are discussed in the context of cellular mechanisms postulated to underlie Li and VPA therapeutic efficacy.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Analysis of Variance
  • Antimanic Agents / therapeutic use*
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / metabolism*
  • Brain / drug effects
  • Brain / metabolism
  • Brain Chemistry / drug effects*
  • Brain Mapping
  • Case-Control Studies
  • Echo-Planar Imaging / methods
  • Female
  • Glutamic Acid / metabolism
  • Glutamine / metabolism
  • Humans
  • Lactic Acid / metabolism
  • Lithium / pharmacology*
  • Lithium / therapeutic use
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Psychiatric Status Rating Scales
  • Valproic Acid / pharmacology*
  • Valproic Acid / therapeutic use
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Antimanic Agents
  • Glutamine
  • Lactic Acid
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Valproic Acid
  • Lithium