Original Articles| Volume 46, ISSUE 12, P1634-1641, December 15, 1999

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


      Background: The clinical effectiveness of lithium may be due to its decreasing the intracellular concentration of myo-inositol and increasing that of its inositol monophosphate precursors, which is known as the inositol depletion hypothesis.
      Methods: Magnetic resonance spectroscopy (MRS) was used to measure the concentration of both myo-inositol (1H MRS) and phosphomonoesters (PME) [31P 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 phosphoinositol (PI) cycle.
      Results: Subjects who received lithium showed a greater increase in PME ratios in response to amphetamine administration than did placebo-treated subjects.
      Conclusions: The present results support the hypothesis that lithium administration blocks the conversion of inositol monophosphates to myo-inositol, and that this effect is especially apparent following PI 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 measure myo-inositol in the brain.
      Keywords: Lithium, inositol, bipolar disorder, amphetamine, magnetic resonance spectroscopy
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