Lithium and valproic acid treatment effects on brain chemistry in bipolar disorder

Friedman, Seth D.; Dager, Stephen R.; Parow, Aimee; Hirashima, Fuyuki; Demopulos, Christina M.; Stoll, Andrew L.; Lyoo, In Kyoon; Dünner, David L.; Renshaw, Perry F.

doi:10.1016/j.biopsych.2004.06.012

Cited by 156 publications

(105 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, the discussion of GABA deficits above may also apply to glutamate increases as a surrogate marker. In patients with bipolar disorder, levels of the combined Glx signal have been reported to decrease with lithium treatment (82). This finding is consistent with the possibility that glutamatergic hyperactivity contributes to the symptoms of mania and is a target for medication development for bipolar disorder (83).…”

Section: Glutamate Glutamine and Gabasupporting

confidence: 62%

MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases

Mason

Krystal

2006

NMR Biomed.

View full text Add to dashboard Cite

Magnetic resonance spectroscopy (MRS) is likely in the near future to play a key role in the process of drug discovery and evaluation. As the pharmaceutical industry seeks biochemical markers of drug delivery, efficacy and toxicity, this non-invasive technique offers numerous ways to study adults and children repeatedly and without ionizing radiation. In this article, we survey an array of the information that MRS offers about neurochemistry in general and psychiatric disorders and their treatment in particular. We also present growing evidence of glial abnormalities in neuropsychiatric disorders and discuss what MRS is contributing to that line of investigation. The third major direction of this article is the discussion of where MRS techniques are headed and how those new techniques can contribute to studies of mechanisms of psychiatric disease and drug discovery.

show abstract

Section: Glutamate Glutamine and Gabasupporting

confidence: 62%

MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases

Mason

Krystal

2006

NMR Biomed.

View full text Add to dashboard Cite

show abstract

“…This would suggest that Cr may not be a stable resonance to be used as an internal standard or reference ratio in bipolar depression research. This certainly warrants further investigation as the current literature in bipolar disorder, although different in methodology, mood state, and brain region, has reported increased creatine (Deicken et al, 2001;Michael et al, 2003Ftrend, Hamakawa et al, 1999Fmen only), decreased creatine (Deicken et al, 2003), or no change in creatine (Hamakawa et al, 1998;Friedman et al, 2004;Cecil et al, 2002;Brambilla et al, 2005;Frey et al, 2005).…”

Section: Discussionmentioning

confidence: 88%

Increased Anterior Cingulate/Medial Prefrontal Cortical Glutamate and Creatine in Bipolar Depression

Frye

Watzl

Banakar

et al. 2007

Neuropsychopharmacol

199

126

View full text Add to dashboard Cite

Proton magnetic resonance spectroscopy ( 1 HMRS) is an in vivo brain imaging method that can be used to investigate psychotropic drug mechanism of action. This study evaluated baseline 1 HMRS spectra of bipolar depressed patients and whether the level of cerebral metabolites changed after an open trial of lamotrigine, an anti-glutamatergic mood stabilizer. Twenty-three bipolar depressed and 12 control subjects underwent a MRS scan of the anterior cingulate/medial prefrontal cortex. The scan was performed on a GE whole-body 1.5 T MRI scanner using single-voxel PRESS (TE/TR ¼ 30/3000 ms, 3 Â 3 Â 3 cm 3 and post-processed offline with LCModel. Baseline CSF-corrected absolute concentrations of glutamate + glutamine ([Glx]), glutamate ([Glu]), and creatine + phosphocreatine ([Cr]) were significantly higher in bipolar depressed subjects vs healthy controls. The non-melancholic subtype had significantly higher baseline [Glx] and [Glu] levels than the melancholic subtype. Remission with lamotrigine was associated with significantly lower post-treatment glutamine ([Gln]) in comparison to non-remission. These data suggest that non-melancholic bipolar depression is characterized by increased glutamate coupled with increased energy expenditure. Lamotrigine appears to reduce glutamine levels associated with treatment remission. Further study is encouraged to determine if these MR spectroscopic markers can delineate drug mechanism of action and subsequent treatment response.

show abstract

“…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. 81 When examined in unmedicated patients, slight elevation of myo-inositol concentration has been observed, but possibly due to small sample size, these results have yet to reach statistical significance. 78 However, in contradiction of such results, inositol and PtdInsP concentrations were found to be significantly lower in lymphocyte derived cell lines derived from bipolar patients compared to controls, 82,83 and reduced levels of PdtIns(4,5)P 2 are seen in platelet membrane from bipolar patients.…”

Section: Preclinical and Clinical Studiesmentioning

confidence: 98%

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

2004

View full text Add to dashboard Cite

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.

show abstract

Lithium and valproic acid treatment effects on brain chemistry in bipolar disorder

Cited by 156 publications

References 76 publications

MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases

MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases

Increased Anterior Cingulate/Medial Prefrontal Cortical Glutamate and Creatine in Bipolar Depression

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

Contact Info

Product

Resources

About