<sup>1</sup>H-MRS of hippocampus in patients after first manic episode

Gigante, Alexandre Duarte; Lafer, Beny; Yatham, Lakshmi N.

doi:10.3109/15622975.2013.819120

Cited by 12 publications

(9 citation statements)

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“…Conflicting results in previous studies may be due to heterogeneous technical approaches for spectra quantification, poor study design, and enrollment of medicated patients at different phases of the illness ( Capizzano et al, 2007 ; Kraguljac et al, 2012 ). Our results are in line with the largest 1H-MRS investigation conducted to date in BD ( Gigante et al, 2014 ), which found no differences with regard to NAA, Cr, mI, Cho, and Glx levels in BD type I patients (medicated and at variable mood states on the day of 1H-MRS scanning) compared to healthy controls.…”

Section: Discussionsupporting

confidence: 91%

“…Also, only three studies have assessed Glu or Glx levels in the hippocampus of subjects with BD. Senaratne et al (2009) and Gigante et al (2014) did not find differences in Glx levels between BD patients and healthy controls. Colla et al (2009) only found elevated Glu concentrations in euthymic BD subjects under lithium treatment compared to healthy controls.…”

Section: Introductionmentioning

confidence: 70%

“…In the last decade, relatively few studies have assessed brain metabolites in the hippocampus of BD patients using 1H-MRS, with a great variability of findings across different investigations ( Capizzano et al, 2007 ; Kraguljac et al, 2012 ; Howells et al, 2013 ). For instance, the largest study (58 BD type I patients versus 27 healthy controls) published so far found no significant differences with regard to NAA, Cr, mI, or Cho levels ( Gigante et al, 2014 ). Also, only three studies have assessed Glu or Glx levels in the hippocampus of subjects with BD.…”

Section: Introductionmentioning

confidence: 99%

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Bimodal Effect of Lithium Plasma Levels on Hippocampal Glutamate Concentrations in Bipolar II Depression: A Pilot Study

Zanetti

Otaduy

Sousa

et al. 2015

International Journal of Neuropsychopharmacology

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Background:The hippocampus has been highly implicated in the pathophysiology of bipolar disorder (BD). Nevertheless, no study has longitudinally evaluated hippocampal metabolite levels in bipolar depression under treatment with lithium.Methods:Nineteen medication-free BD patients (78.9% treatment-naïve and 73.7% with BD type II) presenting an acute depressive episode and 17 healthy controls were studied. Patients were treated for 6 weeks with lithium in an open-label trial. N-acetyl aspartate (NAA), creatine, choline, myo-Inositol, and glutamate levels were assessed in the left hippocampus before (week 0) and after (week 6) lithium treatment using 3T proton magnetic resonance spectroscopy (1H-MRS). The metabolite concentrations were estimated using internal water as reference and voxel segmentation for partial volume correction.Results:At baseline, acutely depressed BD patients and healthy controls exhibited similar hippocampal metabolites concentrations, with no changes after 6 weeks of lithium monotherapy. A significant correlation between antidepressant efficacy and increases in NAA concentration over time was observed. Also, there was a significant positive correlation between the changes in glutamate concentrations over follow-up and plasma lithium levels at endpoint. Mixed effects model analysis revealed a bimodal effect of lithium plasma levels in hippocampal glutamate concentrations: levels of 0.2 to 0.49mmol/L (n=9) were associated with a decrease in glutamate concentrations, whereas the subgroup of BD subjects with “standard” lithium levels (≥0.50 mmol/L; n = 10) showed an overall increase in glutamate concentrations over time.Conclusions:These preliminary results suggest that lithium has a bimodal action in hippocampal glutamate concentration depending on the plasma levels.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

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Bimodal Effect of Lithium Plasma Levels on Hippocampal Glutamate Concentrations in Bipolar II Depression: A Pilot Study

Zanetti

Otaduy

Sousa

et al. 2015

International Journal of Neuropsychopharmacology

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“…91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106 The most consistent finding was reduced NAA, which was detected in 7/15 studies. 91, 92, 93, 94, 97, 100, 103 One study reported increased NAA, 102 and the remainder found no diagnosis-related differences.…”

Section: Discussionmentioning

confidence: 82%

Diagnosis and body mass index effects on hippocampal volumes and neurochemistry in bipolar disorder

et al. 2017

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We previously reported that higher body mass index (BMI) was associated with greater hippocampal glutamate+glutamine in people with bipolar disorder (BD), but not in non-BD healthy comparator subjects (HSs). In the current report, we extend these findings by examining the impact of BD diagnosis and BMI on hippocampal volumes and the concentrations of several additional neurochemicals in 57 early-stage BD patients and 31 HSs. Using 3-T magnetic resonance imaging and magnetic resonance spectroscopy, we measured bilateral hippocampal volumes and the hippocampal concentrations of four neurochemicals relevant to BD: N-acetylaspartate+N-acteylaspartylglutamate (tNAA), creatine+phosphocreatine (Cre), myoinositol (Ins) and glycerophosphocholine+phosphatidylcholine (Cho). We used multivariate factorial analysis of covariance to investigate the impact of diagnosis (patient vs HS) and BMI category (normal weight vs overweight/obese) on these variables. We found a main effect of diagnosis on hippocampal volumes, with patients having smaller hippocampi than HSs. There was no association between BMI and hippocampal volumes. We found diagnosis and BMI effects on hippocampal neurochemistry, with patients having lower Cre, Ins and Cho, and overweight/obese subjects having higher levels of these chemicals. In patient-only models that controlled for clinical and treatment variables, we detected an additional association between higher BMI and lower tNAA that was absent in HSs. To our knowledge, this was the first study to investigate the relative contributions of BD diagnosis and BMI to hippocampal volumes, and only the second to investigate their contributions to hippocampal chemistry. It provides further evidence that diagnosis and elevated BMI both impact limbic brain areas relevant to BD.

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“…However, some studies did not show a decrease in NAA levels [137–139]. Differences in findings may correspond to different brain regions analyzed [137] or disease characteristics of the sample population such as short length of illness [140]. Several studies have shown negative correlations between NAA and illness duration [129,132,141] suggesting that reductions in NAA levels may become more pronounced with the progression of BPD.…”

Section: Mitochondrial Dysfunction In Bpdmentioning

confidence: 99%

Targeting mitochondrially mediated plasticity to develop improved therapeutics for bipolar disorder

Sousa

Machado‐Vieira

Zarate

et al. 2014

Expert Opinion on Therapeutic Targets

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Introduction Bipolar disorder (BPD) is a severe illness with few treatments available. Understanding BPD pathophysiology and identifying potential relevant targets could prove useful for developing new treatments. Remarkably, subtle impairments of mitochondrial function may play an important role in BPD pathophysiology. Areas covered This article focuses on human studies and reviews evidence of mitochondrial dysfunction in BPD as a promising target for the development of new, improved treatments. Mitochondria are crucial for energy production, generated mainly through the electron transport chain (ETC) and play an important role in regulating apoptosis and calcium (Ca2+) signaling as well as synaptic plasticity. Mitochondria move throughout the neurons to provide energy for intracellular signaling. Studies showed polymorphisms of mitochondria-related genes as risk factors for BPD. Postmortem studies in BPD also show decreased ETC activity/expression and increased nitrosative and oxidative stress (OxS) in patient brains. BPD has been also associated with increased OxS, Ca2+ dysregulation and increased proapoptotic signaling in peripheral blood. Neuroimaging studies consistently show decreased energy levels and pH in brains of BPD patients. Expert opinion Targeting mitochondrial function, and their role in energy metabolism, synaptic plasticity and cell survival, may be an important avenue for development of new mood-stabilizing agents.

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¹H-MRS of hippocampus in patients after first manic episode

Abstract: Our results suggest that early in the course of BD there are no alterations in neuronal metabolism or vulnerability in the hippocampus after the first manic episode.

Cited by 12 publications

References 63 publications

Bimodal Effect of Lithium Plasma Levels on Hippocampal Glutamate Concentrations in Bipolar II Depression: A Pilot Study

Bimodal Effect of Lithium Plasma Levels on Hippocampal Glutamate Concentrations in Bipolar II Depression: A Pilot Study

Diagnosis and body mass index effects on hippocampal volumes and neurochemistry in bipolar disorder

Targeting mitochondrially mediated plasticity to develop improved therapeutics for bipolar disorder

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1H-MRS of hippocampus in patients after first manic episode

Abstract: Our results suggest that early in the course of BD there are no alterations in neuronal metabolism or vulnerability in the hippocampus after the first manic episode.

Cited by 12 publications

References 63 publications

Bimodal Effect of Lithium Plasma Levels on Hippocampal Glutamate Concentrations in Bipolar II Depression: A Pilot Study

Bimodal Effect of Lithium Plasma Levels on Hippocampal Glutamate Concentrations in Bipolar II Depression: A Pilot Study

Diagnosis and body mass index effects on hippocampal volumes and neurochemistry in bipolar disorder

Targeting mitochondrially mediated plasticity to develop improved therapeutics for bipolar disorder

Contact Info

Product

Resources

About

¹H-MRS of hippocampus in patients after first manic episode