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      GABA+ levels in postmenopausal women with mild-to-moderate depression : A preliminary study

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          Abstract

          Background:

          It is increasingly being recognized that alterations of the GABAergic system are implicated in the pathophysiology of depression. This study aimed to explore in vivo gamma-aminobutyric acid (GABA) levels in the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) and posterior-cingulate cortex (PCC) of postmenopausal women with depression using magnetic resonance spectroscopy ( 1H-MRS).

          Methods:

          Nineteen postmenopausal women with depression and thirteen healthy controls were enrolled in the study. All subjects underwent 1H-MRS of the ACC/mPFC and PCC using the “MEGA Point Resolved Spectroscopy Sequence” (MEGA-PRESS) technique. The severity of depression was assessed by 17-item Hamilton Depression Scale (HAMD). Quantification of MRS data was performed using Gannet program. Differences of GABA+ levels from patients and controls were tested using one-way analysis of variance. Spearman correlation coefficients were used to evaluate the linear associations between GABA+ levels and HAMD scores, as well as estrogen levels.

          Results:

          Significantly lower GABA+ levels were detected in the ACC/mPFC of postmenopausal women with depression compared to healthy controls ( P = 0.002). No significant correlations were found between 17-HAMD/14-HAMA and GABA+ levels, either in ACC/mPFC ( P = 0.486; r = 0.170/ P = 0.814; r = −0.058) or PCC ( P = 0.887; r = 0.035/ P = 0.987; r = −0.004) in the patients; there is also no significant correlation between GABA+ levels and estrogen levels in patients group (ACC/mPFC: P = 0.629, r = −0.018; PCC: P = 0.861, r = 0.043).

          Conclusion:

          Significantly lower GABA+ levels were found in the ACC/mPFC of postmenopausal women with depression, suggesting that the dysfunction of the GABAergic system may also be involved in the pathogenesis of depression in postmenopausal women.

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          Most cited references42

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          Simultaneous in vivo spectral editing and water suppression.

          Water suppression is typically performed in vivo by exciting the longitudinal magnetization in combination with dephasing, or by using frequency-selective coherence generation. MEGA, a frequency-selective refocusing technique, can be placed into any pulse sequence element designed to generate a Hahn spin-echo or stimulated echo, to dephase transverse water coherences with minimal spectral distortions. Water suppression performance was verified in vivo using stimulated echo acquisition mode (STEAM) localization, which provided water suppression comparable with that achieved with four selective pulses in 3,1-DRYSTEAM. The advantage of the proposed method was exploited for editing J-coupled resonances. Using a double-banded pulse that selectively inverts a J-coupling partner and simultaneously suppresses water, efficient metabolite editing was achieved in the point resolved spectroscopy (PRESS) and STEAM sequences in which MEGA was incorporated. To illustrate the efficiency of the method, the detection of gamma-aminobutyric acid (GABA) was demonstrated, with minimal contributions from macromolecules and overlying singlet peaks at 4 T. The estimated occipital GABA concentration was consistent with previous reports, suggesting that editing for GABA is efficient when based on MEGA at high field strengths.
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            Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression.

            Measurement of cortical gamma-aminobutyric acid (GABA) and glutamate concentrations is possible using proton magnetic resonance spectroscopy. An initial report, using this technique, suggested that occipital cortex GABA concentrations are reduced in patients with major depressive disorder (MDD) relative to healthy comparison subjects. To replicate the GABA findings in a larger sample of MDD patients, to examine the clinical correlates of the GABA reductions in these subjects, and to examine other critical metabolite levels. Study for association. Academic clinical research program. The GABA measurements were made on 38 healthy control subjects and 33 depressed subjects. Occipital cortex metabolite levels were measured using proton magnetic resonance spectroscopy. The levels of occipital cortex GABA, glutamate, N-acetylaspartate, aspartate, creatine, and choline-containing compounds, along with several measures of tissue composition, were compared between the 2 groups. Depressed subjects had significantly lower occipital cortex GABA concentrations compared with healthy controls (P =.01). In addition, mean glutamate levels were significantly increased in depressed subjects compared with healthy controls (P<.001). Significant reductions in the percentage of solid tissue (P =.009) and the percentage of white matter (P =.04) in the voxel were also observed. An examination of a combined database including subjects from the original study suggests that GABA and glutamate concentrations differ among MDD subtypes. The study replicates the findings of decreased GABA concentrations in the occipital cortex of subjects with MDD. It also demonstrates that there is a change in the ratio of excitatory-inhibitory neurotransmitter levels in the cortex of depressed subjects that may be related to altered brain function. Last, the combined data set suggests that magnetic resonance spectroscopy GABA measures may serve as a biological marker for a subtype of MDD.
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              Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole.

              Growing evidence indicates that glia pathology and amino-acid neurotransmitter system abnormalities contribute to the pathophysiology and possibly the pathogenesis of major depressive disorder. This study investigates changes in glial function occurring in the rat prefrontal cortex (PFC) after chronic unpredictable stress (CUS), a rodent model of depression. Furthermore, we analyzed the effects of riluzole, a Food and Drug Administration-approved drug for the treatment of amyotrophic laterosclerosis, known to modulate glutamate release and facilate glutamate uptake, on CUS-induced glial dysfunction and depressive-like behaviors. We provide the first experimental evidence that chronic stress impairs cortical glial function. Animals exposed to CUS and showing behavioral deficits in sucrose preference and active avoidance exhibited significant decreases in 13C-acetate metabolism reflecting glial cell metabolism, and glial fibrillary associated protein (GFAP) mRNA expression in the PFC. The cellular, metabolic and behavioral alterations induced by CUS were reversed and/or blocked by chronic treatment with the glutamate-modulating drug riluzole. The beneficial effects of riluzole on CUS-induced anhedonia and helplessness demonstrate the antidepressant action of riluzole in rodents. Riluzole treatment also reversed CUS-induced reductions in glial metabolism and GFAP mRNA expression. Our results are consistent with recent open-label clinical trials showing the drug's effect in mood and anxiety disorders. This study provides further validation of hypothesis that glial dysfunction and disrupted amino-acid neurotransmission contribute to the pathophysiology of depression and that modulation of glutamate metabolism, uptake and/or release represent viable targets for antidepressant drug development.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                September 2016
                30 September 2016
                : 95
                : 39
                : e4918
                Affiliations
                [a ]Shandong Medical Imaging Research Institute Affiliated to Shandong University
                [b ]No. 2 Affiliated Hospital of Shandong Traditional Chinese Medicine University
                [c ]Affiliated Eye Hospital of Shandong Traditional Chinese Medicine University
                [d ]Qi Lu Hospital of Shandong University, Jinan, China
                [e ]Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine
                [f ]FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD.
                Author notes
                []Correspondence: Guangbin Wang, Shandong Medical Imaging Research Institute Affiliated to Shandong University, No. 324, Jing-Wu Road, Jinan, China (e-mail: wgb7932596@ 123456hotmail.com ).
                Article
                04918
                10.1097/MD.0000000000004918
                5265922
                27684829
                7eed5476-96a2-4d40-b2ac-d63231cd0544
                Copyright © 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially. http://creativecommons.org/licenses/by-nc/4.0

                History
                : 17 July 2016
                : 24 August 2016
                : 28 August 2016
                Categories
                5300
                Research Article
                Clinical Trial/Experimental Study
                Custom metadata
                TRUE

                depression,gaba+,hamd/hama,mega-press,postmenopausal
                depression, gaba+, hamd/hama, mega-press, postmenopausal

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