Bipolar disorder and myo-inositol: a review of the magnetic resonance spectroscopy findings.
OBJECTIVE
Myo-inositol is an important component of the phosphatidylinositol second messenger system (PI-cycle). Alterations in PI-cycle activity have been suggested to be involved in the pathophysiology and/or treatment of bipolar disorder. More specifically, lithium has been suggested to act primarily by lowering myo-inositol concentrations, the so-called inositol-depletion hypothesis. myo-Inositol concentrations can be measured in vivo with magnetic resonance spectroscopy (MRS).


METHODS
The current review primarily examines animal and human MRS studies that evaluated the role of myo-inositol in bipolar illness and treatment.


RESULTS
Studies have been carried out in patients who are manic, depressed, and euthymic, both on and off treatment. However, there are several limitations of these studies.


CONCLUSIONS
The preclinical and clinical MRS findings were generally supportive of the involvement of myo-inositol in bipolar disorder and its treatment. Overall, in bipolar patients who are manic or depressed there are abnormalities in brain myo-inositol concentrations, with changes in frontal and temporal lobes, as well as the cingulate gyrus and basal ganglia. These abnormalities are not seen in either euthymic patients or healthy controls, possibly due to a normalizing effect of treatment with either lithium or sodium valproate. There is also increasing evidence that sodium valproate may also act upon the PI-cycle. Nonetheless, it remains uncertain if these changes in myo-inositol concentration are primary or secondary. Findings regarding the specific inositol-depletion hypothesis are also generally supportive in acutely ill patients, although it is not yet possible to definitively confirm or refute this hypothesis based on the current MRS evidence.
Silverstone
Peter H
PH
Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada. peter.silverstone@ualberta.ca
McGrath
Brent M
BM
Kim
Hyeonjin
H
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001479:Basal Ganglia / Q000378:metabolism; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D005625:Frontal Lobe / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000172:deficiency*; D016651:Lithium Carbonate / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy; D013702:Temporal Lobe / Q000378:metabolism; D014635:Valproic Acid / Q000627:therapeutic use
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D016651:Lithium Carbonate; D007294:Inositol; D014635:Valproic Acid