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.
Friedman
Seth D
SD
Department of Radiology, University of Washington, Seattle, Washington, USA. seth@u.washington.edu
Dager
Stephen R
SR
Parow
Aimee
A
Hirashima
Fuyuki
F
Demopulos
Christina
C
Stoll
Andrew L
AL
Lyoo
In Kyoon
IK
Dunner
David L
DL
Renshaw
Perry F
PF
D000328:Adult; D000704:Analysis of Variance; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D001931:Brain Mapping; D016022:Case-Control Studies; D017352:Echo-Planar Imaging / Q000379:methods; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology* / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D011569:Psychiatric Status Rating Scales; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018692:Antimanic Agents; D005973:Glutamine; D019344:Lactic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D008094:Lithium