Behavioral reversal of lithium effects by four 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

Robert H. Belmaker; Galila Agam; Dietrich Van Calker; Mary H. Richards; Ora Kofman

doi:10.1016/S0893-133X(98)00017-7

Behavioral reversal of lithium effects by four 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

Robert H. Belmaker, Galila Agam, Dietrich Van Calker, Mary H. Richards, Ora Kofman

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

Abstract

The inositol depletion hypothesis of lithium (Li) action has been criticized, because depletion of inositol after chronic Li treatment has not been reproducible, effects of inositol to reverse Li-induced behaviors occurred also with epi-inositol, a unnatural isomer, and because inositol is ubiquitous in brain and 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 hypothalamus, a region not previously examined; that behavioral effects of four different inositol isomers including epi-inositol correlate perfectly with their biochemical effects; and that inositol in postmortem human brain is reduced by 25% in frontal cortex of bipolars and suicides as compared with controls. Because inositol in postmortem brain is reduced and not increased in bipolar patients, the relationship between inositol, lithium, and affective disorder is complex.

Original language	English
Pages (from-to)	220-232
Number of pages	13
Journal	Neuropsychopharmacology
Volume	19
Issue number	3
DOIs	https://doi.org/10.1016/S0893-133X(98)00017-7
State	Published - 1 Sep 1998
Externally published	Yes

Keywords

Bipolar disorder
Epi-inositol
Frontal cortex
Hypothalamus
Inositol
Myo-inositol

ASJC Scopus subject areas

Pharmacology
Psychiatry and Mental health

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Belmaker, R. H., Agam, G., Van Calker, D., Richards, M. H., & Kofman, O. (1998). Behavioral reversal of lithium effects by four 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. Neuropsychopharmacology, 19(3), 220-232. https://doi.org/10.1016/S0893-133X(98)00017-7

Belmaker, Robert H. ; Agam, Galila ; Van Calker, Dietrich et al. / Behavioral reversal of lithium effects by four 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. In: Neuropsychopharmacology. 1998 ; Vol. 19, No. 3. pp. 220-232.

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title = "Behavioral reversal of lithium effects by four 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",

abstract = "The inositol depletion hypothesis of lithium (Li) action has been criticized, because depletion of inositol after chronic Li treatment has not been reproducible, effects of inositol to reverse Li-induced behaviors occurred also with epi-inositol, a unnatural isomer, and because inositol is ubiquitous in brain and 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 hypothalamus, a region not previously examined; that behavioral effects of four different inositol isomers including epi-inositol correlate perfectly with their biochemical effects; and that inositol in postmortem human brain is reduced by 25% in frontal cortex of bipolars and suicides as compared with controls. Because inositol in postmortem brain is reduced and not increased in bipolar patients, the relationship between inositol, lithium, and affective disorder is complex.",

keywords = "Bipolar disorder, Epi-inositol, Frontal cortex, Hypothalamus, Inositol, Myo-inositol",

author = "Belmaker, {Robert H.} and Galila Agam and {Van Calker}, Dietrich and Richards, {Mary H.} and Ora Kofman",

note = "Funding Information: We thank the numerous collaborators on various aspects of our inositol studies: Hady Shimon, B.Sc., Yardena Patishi, M.Sc., Yuli Bersudsky, M.D., Ph.D., Beate Lubrich, M.Sc., El-lena Sobelev, M.Sc., Joseph Shapiro, M.D., Ph.D., and Joseph Levine, M.D. We thank Ellana Shellem for typing and editorial assistance. We thank Joel Kleinman and Thomas Hyde for human brain samples from their collection. We also thank William R. Sherman of Washington University, St. Louis, MO for his unstinting encouragement, advice, and support of inositol studies in Beersheva. This research was partially supported by a grant from the Stanley Foundation to Galila Agam, Ph.D. and a GIF grant No I-245-098.02/92 to Ora Kofman PhD., R.H. Belmaker, M.D., and Dietrich van Calker, M.D., Ph.D",

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Belmaker, RH, Agam, G, Van Calker, D, Richards, MH & Kofman, O 1998, 'Behavioral reversal of lithium effects by four 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', Neuropsychopharmacology, vol. 19, no. 3, pp. 220-232. https://doi.org/10.1016/S0893-133X(98)00017-7

Behavioral reversal of lithium effects by four 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. / Belmaker, Robert H.; Agam, Galila; Van Calker, Dietrich et al.
In: Neuropsychopharmacology, Vol. 19, No. 3, 01.09.1998, p. 220-232.

Research output: Contribution to journal › Article › peer-review

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T2 - Depletion by chronic lithium of brain inositol is specific to hypothalamus, and inositol levels may be abnormal in postmortem brain from bipolar patients

AU - Belmaker, Robert H.

AU - Agam, Galila

AU - Van Calker, Dietrich

AU - Richards, Mary H.

AU - Kofman, Ora

N1 - Funding Information: We thank the numerous collaborators on various aspects of our inositol studies: Hady Shimon, B.Sc., Yardena Patishi, M.Sc., Yuli Bersudsky, M.D., Ph.D., Beate Lubrich, M.Sc., El-lena Sobelev, M.Sc., Joseph Shapiro, M.D., Ph.D., and Joseph Levine, M.D. We thank Ellana Shellem for typing and editorial assistance. We thank Joel Kleinman and Thomas Hyde for human brain samples from their collection. We also thank William R. Sherman of Washington University, St. Louis, MO for his unstinting encouragement, advice, and support of inositol studies in Beersheva. This research was partially supported by a grant from the Stanley Foundation to Galila Agam, Ph.D. and a GIF grant No I-245-098.02/92 to Ora Kofman PhD., R.H. Belmaker, M.D., and Dietrich van Calker, M.D., Ph.D

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AB - The inositol depletion hypothesis of lithium (Li) action has been criticized, because depletion of inositol after chronic Li treatment has not been reproducible, effects of inositol to reverse Li-induced behaviors occurred also with epi-inositol, a unnatural isomer, and because inositol is ubiquitous in brain and 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 hypothalamus, a region not previously examined; that behavioral effects of four different inositol isomers including epi-inositol correlate perfectly with their biochemical effects; and that inositol in postmortem human brain is reduced by 25% in frontal cortex of bipolars and suicides as compared with controls. Because inositol in postmortem brain is reduced and not increased in bipolar patients, the relationship between inositol, lithium, and affective disorder is complex.

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KW - Hypothalamus

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KW - Myo-inositol

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Belmaker RH, Agam G, Van Calker D, Richards MH, Kofman O. Behavioral reversal of lithium effects by four 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. Neuropsychopharmacology. 1998 Sep 1;19(3):220-232. doi: 10.1016/S0893-133X(98)00017-7

Behavioral reversal of lithium effects by four 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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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