Myo-inositol in depressive and healthy subjects determined by frontal 1H-magnetic resonance spectroscopy at 1.5 tesla

Frey, Richard; Metzler, Debra J.; Fischer, Peter; Heiden, A.; Scharfetter, Joachim; Moser, Ewald; Kasper, Siegfried

doi:10.1016/s0022-3956(98)00033-8

Cited by 87 publications

(63 citation statements)

References 20 publications

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“…The fact that the adult IMPA1 À/À mice did not show reduced inositol levels in various brain regions does not rule out inositol depletion as a mechanism of the observed seizures. Several pools of inositol are suggested to exist in the brain (Bersudsky et al, 1994;Brand et al, 1993;Fisher et al, 2002;Frey et al, 1998;Novak et al, 1999Novak et al, , 2000a and the IMPA1-dependent inositol pool likely makes up only a small, possibly spatially delineated but clearly significant part. Actually, inositol depletion as a result of dietary inositol restriction (Shaldubina et al, 2006b) or hyponatremia (Bersudsky et al, 1994) has been shown not to sensitize pilocarpine-induced seizures.…”

Section: Discussionmentioning

confidence: 99%

IMPA1 is Essential for Embryonic Development and Lithium-Like Pilocarpine Sensitivity

Cryns¹,

Shamir

Acker

et al. 2007

Neuropsychopharmacol

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Lithium has been the standard pharmacological treatment for bipolar disorder over the last 50 years; however, the molecular targets through which lithium exerts its therapeutic effects are still not defined. We characterized the phenotype of mice with a dysfunctional IMPA1 gene (IMPA1 À/À ) to study the in vivo physiological functions of IMPA1, in general, and more specifically its potential role as a molecular target in mediating lithium-dependent physiological effects. Homozygote IMPA1 À/À mice died in utero between days 9.5 and 10.5 post coitum (p.c.) demonstrating the importance of IMPA1 in early embryonic development. Intriguingly, the embryonic lethality could be reversed by myo-inositol supplementation via the pregnant mothers. In brains of adult IMPA1 À/À mice, IMPase activity levels were found to be reduced (up to 65% in hippocampus); however, inositol levels were not found to be altered. Behavioral analysis of the IMPA1 À/À mice indicated an increased motor activity in both the open-field test and the forced-swim test as well as a strongly increased sensitivity to pilocarpine-induced seizures, the latter supporting the idea that IMPA1 represents a physiologically relevant target for lithium. In conclusion the IMPA1 À/À mouse represents a novel model to study inositol homeostasis, and indicates that genetic inactivation of IMPA1 can mimic some actions of lithium.

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Section: Discussionmentioning

confidence: 99%

IMPA1 is Essential for Embryonic Development and Lithium-Like Pilocarpine Sensitivity

Cryns¹,

Shamir

Acker

et al. 2007

Neuropsychopharmacol

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“…It is therefore not surprising that the use of metabolite ratios in clinical proton MRS studies of depressed subjects led to conflicting results. [43][44][45][46][47] Moreover, also the effects of drug administration would have been overseen, because the increased Ins concentrations lead to elevated Ins/Cr ratios which are not significantly different from those observed in the Stress group.…”

Section: Discussionmentioning

confidence: 99%

Substance P receptor antagonist and clomipramine prevent stress-induced alterations in cerebral metabolites, cytogenesis in the dentate gyrus and hippocampal volume

et al. 2002

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The neuropeptide substance P and its receptor, the neurokinin 1 receptor (NK 1 R) have been proposed as possible targets for new antidepressant therapies. The present study investigated the effect of the NK 1 R antagonist L-760,735 and the tricyclic antidepressant clomipramine in the chronic psychosocial stress paradigm of adult male tree shrews. Animals were subjected to a 7-day period of psychosocial stress before the onset of daily oral administration of L-760,735 (10 mg kg −1 day −1 ) or clomipramine (50 mg kg −1 day −1 ). The psychosocial stress continued throughout the treatment period of 28 days. Brain metabolite concentrations were determined in vivo by proton magnetic resonance spectroscopy. Cell proliferation in the dentate gyrus and hippocampal volume were measured post mortem. Stress significantly decreased in vivo concentrations of N-acetyl-aspartate (−14%), creatine and phosphocreatine (−15%) and choline-containing compounds (−15%). The proliferation rate of the granule precursor cells in the dentate gyrus was reduced (−45%), and hippocampal volume was decreased (−14%). The stress-induced changes of brain metabolites, hippocampal volume and dentate cytogenesis rate were prevented by concomitant drug administration. Elevated myoinositol concentrations after both treatments hint to an astrocytic enhancement. These results suggest that-despite a different pharmacological profile-the NK 1 R antagonist L-760,735, a member of a novel class of antidepressant drugs, has comparable neurobiological efficacy to tricyclic antidepressants such as clomipramine. Molecular Psychiatry (2002) 7, 933-941.

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“…Although the decrease observed in NAA+NAAG was only significant to the Cr ratio, Cr was not significantly different in MDD patients. NAA has been associated with neuronal integrity [27], whereas increases in mI content have been interpreted as representing either glial proliferation or an increase in glial cell size and, therefore, have been considered markers of inflammation in the brain [29]. It has also been demonstrated that high levels of mI are present in some types of neurons, where it is involved in second messenger signaling [29].…”

Section: Discussionmentioning

confidence: 99%

“…NAA has been associated with neuronal integrity [27], whereas increases in mI content have been interpreted as representing either glial proliferation or an increase in glial cell size and, therefore, have been considered markers of inflammation in the brain [29]. It has also been demonstrated that high levels of mI are present in some types of neurons, where it is involved in second messenger signaling [29]. Though the present methodology is not capable of differentiating between mI level in glial or neuronal cells, or of determining whether this increase reflects compensatory changes related to other pathogenic processes (further research is needed), these results do indicate an alteration in PCC metabolite levels and thus support the involvement of the PCC in depression.…”

Section: Discussionmentioning

confidence: 99%

“…Myoinositol (mI), one of the metabolites analyzed by MRS, is a precursor molecule for several brain metabolites. It participates in signaling processes in the phosphatidylcholine system and is involved in the regulation of cellular osmolarity; therefore, it has been considered as a possible marker of inflammatory responses in the brain and of glial cell loss [27,29]. Levels of mI have been found to be lower in the anterior cingulate cortex [21], as has the mI/Cr (creatine) ratio in the left and right prefrontal regions [30] and in the prefrontal and anterior cingulate cortices in medicated patients after several weeks of wash-out [31].…”

Section: Introductionmentioning

confidence: 99%

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Increased myo-inositol in the posterior cingulate cortex in first-episode major depressive patients

Granados-Domínguez¹,

Flores-Gutiérrez²,

Alcauter³

et al. 2013

ABB

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Major depressive disorder (MDD) is a severe, disabling pathology characterized, in addition to affective, cognitive and motor symptoms, by self-focused attention and rumination. During recursive self-focused processes and rumination, the posterior cingulate cortex (PCC) is activated. In vivo proton magnetic resonance spectroscopy (MRS) is a noninvasive imaging technique that can directly assess living biochemistry in localized brain regions. The aim of this study, therefore, was to use 1 H-MRS as a means of analyzing brain metabolites in the PCC of a group of first-episode, unmedicated MDD patients. PCC metabolite levels were analyzed at 3-T in a single voxel located bilaterally over the PCC in 7 patients diagnosed for the first time with MDD and with no previous pharmacological treatment, as well as in 9 control subjects. Differences in metabolite levels between groups were compared using independent t-tests. Myo-inositol was significantly higher, and NAA + NAAG/Cr significantly lower, in MDD patients than in controls. The other brain metabolites showed no statistical differences. The present results suggest that alterations in PCC metabolite levels are likely involved in MDD pathophysiology, and may help to improve our understanding of MDD and the role of the PCC in some symptoms of depression.

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Myo-inositol in depressive and healthy subjects determined by frontal 1H-magnetic resonance spectroscopy at 1.5 tesla

Cited by 87 publications

References 20 publications

IMPA1 is Essential for Embryonic Development and Lithium-Like Pilocarpine Sensitivity

IMPA1 is Essential for Embryonic Development and Lithium-Like Pilocarpine Sensitivity

Substance P receptor antagonist and clomipramine prevent stress-induced alterations in cerebral metabolites, cytogenesis in the dentate gyrus and hippocampal volume

Increased myo-inositol in the posterior cingulate cortex in first-episode major depressive patients

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