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

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.