Effects of lithium and amphetamine on inositol metabolism in the human brain as measured by H-1 and P-31 MRS

Background: The clinical effectiveness of lithium may be due to its decreas ing the intracellular concentration of myo-inositol and increasing that of its inositol monophosphate precursors, which is known as the inositol deple tion hypothesis. Methods: Magnetic resonance spectroscopy (MRS) was used to measure the conc entration of both myo-inositol (H-1 MRS) and phosphomonoesters (PME) [P-31 MRS], in healthy volunteers in a double-blind placebo-controlled study. MRS measurements were made at baseline, again on the 7th day of lithium (1200 mg, n = 10) or placebo (n = 6) administration, and again on day 8, 2 hours following oral administration of 20 mg dextroamphetamine to stimulate the p hosphoinositol (PI) cycle. Results: Subjects who received lithium showed a greater increase in PME rat ios in response to amphetamine administration than did placebo-treated subj ects. Conclusions: The present results support the hypothesis that lithium admini stration blocks the conversion of inositol monophosphates to myo-inositol, and that this effect is especially apparent following PT cycle stimulation. The effects of lithium treatment on myo-inositol in healthy volunteers in vivo are uncertain, and may have to await improvements in the ability to me asure myo-inositol in the brain. Biol Psychiatry 1999;46:1634-1641 (C) 1999 Society of Biological Psychiatry.