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      Brain volumetric and metabolic correlates of electroconvulsive therapy for treatment-resistant depression: a longitudinal neuroimaging study

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          Abstract

          Recent research suggests that neuroplastic and neuroinflammatory changes may account for the mode of action of electroconvulsive therapy (ECT), although extant data do not allow for a clear disambiguation between these two hypotheses. Multimodal neuroimaging approaches (for example, combining structural and metabolic information) may help in clarifying this issue. Here we aimed to assess longitudinal changes in (i) regional gray matter (GM) volumes and (ii) hippocampal metabolite concentrations throughout an acute course of bitemporal ECT, as well as (iii) to determine the association between imaging changes and clinical improvement. We assessed 12 patients with treatment-resistant depression (TRD) at four time points (pre-treatment, after the first ECT session, after the ninth ECT session and 15 days after ECT course completion) and 10 healthy participants at two time points, 5 weeks apart. Patients with TRD showed bilateral medial temporal lobe (MTL) and perigenual anterior cingulate cortex volume increases. Left MTL volume increase was associated with (i) a hippocampal N-acetylaspartate concentration decrease, (ii) a hippocampal Glutamate+Glutamine concentration increase and (iii) significant clinical improvement. The observed findings are, in part, compatible with both neuroplastic and neuroinflammatory changes induced by ECT. We postulate that such phenomena may be interrelated, therefore reconciling the neuroplasticity and neuroinflammatory hypotheses of ECT action.

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          Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression.

          The authors conducted a systematic review and meta-analysis of ketamine and other N-methyl-d-aspartate (NMDA) receptor antagonists in the treatment of major depression.
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            Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation.

            Although endogenous recruitment of adult neural stem cells has been proposed as a therapeutic strategy, clinical approaches for achieving this are lacking. Here, we show that metformin, a widely used drug, promotes neurogenesis and enhances spatial memory formation. Specifically, we show that an atypical PKC-CBP pathway is essential for the normal genesis of neurons from neural precursors and that metformin activates this pathway to promote rodent and human neurogenesis in culture. Metformin also enhances neurogenesis in the adult mouse brain in a CBP-dependent fashion, and in so doing enhances spatial reversal learning in the water maze. Thus, metformin, by activating an aPKC-CBP pathway, recruits neural stem cells and enhances neural function, thereby providing a candidate pharmacological approach for nervous system therapy. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Depression and hippocampal neurogenesis: a road to remission?

              Adult-generated hippocampal neurons are required for mood control and antidepressant efficacy, raising hopes that someday we can harness the power of new neurons to treat mood disorders such as depression. However, conflicting findings from preclinical research--involving stress, depression, and neurogenesis--highlight the complexity of considering neurogenesis as a road to remission from depression. To reconcile differences in the literature, we introduce the "neurogenic interactome," a platform from which to consider the diverse and dynamic factors regulating neurogenesis. We propose consideration of the varying perspectives--system, region, and local regulation of neurogenesis--offered by the interactome and exchange of ideas between the fields of learning and memory and mood disorder research to clarify the role of neurogenesis in the etiology and treatment of depression.
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                Author and article information

                Journal
                Transl Psychiatry
                Transl Psychiatry
                Translational Psychiatry
                Nature Publishing Group
                2158-3188
                February 2017
                07 February 2017
                1 February 2017
                : 7
                : 2
                : e1023
                Affiliations
                [1 ]Department of Psychiatry, Bellvitge University Hospital-IDIBELL , Barcelona, Spain
                [2 ]Department of Clinical Sciences, School of Medicine, University of Barcelona , Barcelona, Spain
                [3 ]Magnetic Resonance Department, Inscanner SL , Alicante, Spain
                [4 ]Carlos III Health Institute, CIBERSAM , Madrid, Spain
                [5 ]Mental Health Department, Parc Taulí Sabadell, Universitat Autònoma de Barcelona , Barcelona, Spain
                [6 ]School of Psychiatry, University of New South Wales (UNSW) and Black Dog Institute, Randwick , Sydney, NSW, Australia
                [7 ]MRI Research Unit, Radiology Department, Hospital del Mar , Barcelona, Spain
                [8 ]Department of Psychobiology and Methodology in Health Sciences, Universitat Autònoma de Barcelona , Barcelona, Spain
                Author notes
                [* ]Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Feixa Llarga s/n , Hospitalet de Llobregat, 08907 Barcelona, Spain E-mail: jmenchon@ 123456idibell.cat
                [* ]Mental Health Department, Parc Taulí Sabadell, Universitat Autònoma de Barcelona , Parc Taulí 1, Sabadell, 08208 Barcelona, Spain. E-mail: ncardoner@ 123456tauli.cat
                Article
                tp2016267
                10.1038/tp.2016.267
                5438019
                28170003
                9f30da31-e174-4854-a869-7ba19d9d394d
                Copyright © 2017 The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 09 August 2016
                : 12 October 2016
                : 13 November 2016
                Categories
                Original Article

                Clinical Psychology & Psychiatry
                Clinical Psychology & Psychiatry

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