BEHAVIORAL REVERSAL OF LITHIUM EFFECTS BY 4 INOSITOL ISOMERS CORRELATES PERFECTLY WITH BIOCHEMICAL EFFECTS ON THE PI-CYCLE - DEPLETION BY CHRONIC LITHIUM OF BRAIN INOSITOL IS SPECIFIC TO HYPOTHALAMUS, AND INOSITOL LEVELS MAY BE ABNORMAL IN POSTMORTEM BRAIN FROM BIPOLAR PATIENTS

The inositol depletion hypothesis of lithium (Li) action has been crit icized, because depletion of inositol after chronic Li treatment has n ot been reproducible, effects of inositol to reverse Li-induced behavi ors occurred also with epi-inositol, a unnatural isomer, and because i nositol is ubiquitous in brain anti hard to relate to the pathogenesis of affective disorder. Therefore, we review our studies showing that lithium depletion of brain inositol occurs chronically in the hypothal amus, it region not previously examined; that behavioral effects of fo ur different inositol isomers including epi-inositol correlate perfect ly with their biochemical effects; and that inositol in postmortem hum an brain is reduced by 25% in frontal cortex of bipolars and suicides as compared with controls. Because inositol in postmortem brain is red uced and not increased in bipolar patients, the relationship between i nositol, lithium, and affective disorder is complex. (C) 1998 American College of Neuropsychopharmacology. Published by Elsevier Science Inc .