Chronic treatment with both lithium and sodium valproate may normalize phosphoinositol cycle activity in bipolar patients

Silverstone, Peter H.; Wu, Rui; O'Donnell, Tina; Ulrich, Michelle; Asghar, Sheila; Hanstock, Christopher C.

doi:10.1002/hup.420

Cited by 77 publications

(48 citation statements)

References 36 publications

(53 reference statements)

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“…Several studies utilizing 31 P MRS suggest that euthymic BPD patients on treatment have PME concentrations that are not significantly different from healthy controls (Kato et al, 1994b(Kato et al, , 1995Murashita et al, 2000;Silverstone et al, 2002;Hamakawa et al, 2004), although other studies did find reduced concentrations (Kato et al, 1993(Kato et al, , 1994a.…”

Section: Euthymic Patientsmentioning

confidence: 96%

A review of the possible relevance of inositol and the phosphatidylinositol second messenger system (PI‐cycle) to psychiatric disorders—focus on magnetic resonance spectroscopy (MRS) studies

Kim

McGrath

Silverstone

2005

Human Psychopharmacology

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119

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Myo-inositol is an important part of the phosphatidylinositol second messenger system (PI-cycle). Abnormalities in nerve cell myo-inositol levels and/or PI-cycle regulation has been suggested as being involved in the pathophysiology and/or treatment of many psychiatric disorders including bipolar disorder, major depressive disorder, panic disorder, obsessive-compulsive disorder, eating disorders and schizophrenia. This review examines the metabolism and biochemical importance of myo-inositol and the PI-cycle. It relates this to the current in vivo evidence for myo-inositol and PI-cycle involvement in these psychiatric disorders, particularly focusing upon the magnetic resonance spectroscopy (MRS) findings in patient studies to date. From this review it is concluded that while the evidence suggests probable relevance to the pathophysiology and/or treatment of bipolar disorder, there is much less support for a significant role for the PI-cycle or myo-inositol in any other psychiatric disorder. More definitive investigation is required before PI-cycle dysfunction can be considered specific to bipolar disorder.

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Section: Euthymic Patientsmentioning

confidence: 96%

A review of the possible relevance of inositol and the phosphatidylinositol second messenger system (PI‐cycle) to psychiatric disorders—focus on magnetic resonance spectroscopy (MRS) studies

Kim

McGrath

Silverstone

2005

Human Psychopharmacology

Self Cite

119

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“…The majority show results consistent with decreased myo-inositol or increased InsP 1 , [74][75][76][77][78] however, some find no difference. 79,80 The failure to find differences in chronically treated patients has been interpreted as treatment leading to normalization of signaling. Changes may also reflect spatial heterogeneity in Li þ and VPA responses, and a recent study found inositol reduced by Li þ in white matter, but increased in grey matter.…”

Section: Preclinical and Clinical Studiesmentioning

confidence: 99%

Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited

2004

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Inositol, a simple six-carbon sugar, forms the basis of a number of important intracellular signaling molecules. Over the last 35 years, a series of biochemical and cell biological experiments have shown that lithium (Li þ ) reduces the cellular concentration of myo-inositol and as a consequence attenuates signaling within the cell. Based on these observations, inositol-depletion was proposed as a therapeutic mechanism in the treatment of bipolar mood disorder. Recent results have added significant new dimensions to the original hypothesis. However, despite a number of clinical studies, this hypothesis still remains to be either proven or refuted. In this review of our current knowledge, I will consider where the inositol-depletion hypothesis stands today and how it may be further investigated in the future.

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“…However, this study is limited by most of the patients receiving concomitant medications, confounding interpretation of results. In contrast, other studies report no change in cortical [35,36] or anterior cingulate [37] mI in euthymic bipolar patients treated with lithium compared with healthy control subjects. The finding of reduction in mI has not been observed in healthy subjects after lithium administration and seems to be specific to patients with bipolar disorder [38].…”

Section: Myo-inositolmentioning

confidence: 62%

Neurochemical predictors of response to pharmacologic treatments for bipolar disorder

DelBello

Strakowski²

2004

Curr Psychiatry Rep

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Bipolar disorder is a common psychiatric disorder that is characterized by recurrent episodes of mania and often depression. Mood stabilizers and antipsychotics are first-line pharmacologic options for patients with bipolar disorder. However, the exact mechanisms by which these medications exert the mood stabilizing effects are unknown. Additionally, individuals with bipolar disorder often try several medications unsuccessfully before achieving mood stabilization. Magnetic resonance spectroscopy (MRS) is a noninvasive neuroimaging technique that can be used to identify the neurochemical effects and predictors of response to medications commonly used to treat bipolar disorder. MRS may facilitate targeted treatment interventions and decrease the morbidity and mortality associated with this illness. Examining the mechanisms of action of pharmacologic agents used to treat bipolar disorder may clarify the neurophysiologic basis of bipolar disorder. We will review recent MRS investigations that have evaluated the neurochemical effects of pharmacologic treatments and predictors of treatment response in patients with bipolar disorder.

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Chronic treatment with both lithium and sodium valproate may normalize phosphoinositol cycle activity in bipolar patients

Cited by 77 publications

References 36 publications

A review of the possible relevance of inositol and the phosphatidylinositol second messenger system (PI‐cycle) to psychiatric disorders—focus on magnetic resonance spectroscopy (MRS) studies

A review of the possible relevance of inositol and the phosphatidylinositol second messenger system (PI‐cycle) to psychiatric disorders—focus on magnetic resonance spectroscopy (MRS) studies

Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited

Neurochemical predictors of response to pharmacologic treatments for bipolar disorder

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