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Intrinsic Connectivity Networks of Glutamate-Mediated Antidepressant Response: A Neuroimaging Review
Conventional monoamine-based pharmacotherapy, considered the first-line treatment for major depressive disorder (MDD), has several challenges, including high rates of non-response. To address these challenges, preclinical and clinical studies have sought to characterize antidepressant response throu...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9199367/ https://www.ncbi.nlm.nih.gov/pubmed/35722550 http://dx.doi.org/10.3389/fpsyt.2022.864902 |
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author | Demchenko, Ilya Tassone, Vanessa K. Kennedy, Sidney H. Dunlop, Katharine Bhat, Venkat |
author_facet | Demchenko, Ilya Tassone, Vanessa K. Kennedy, Sidney H. Dunlop, Katharine Bhat, Venkat |
author_sort | Demchenko, Ilya |
collection | PubMed |
description | Conventional monoamine-based pharmacotherapy, considered the first-line treatment for major depressive disorder (MDD), has several challenges, including high rates of non-response. To address these challenges, preclinical and clinical studies have sought to characterize antidepressant response through monoamine-independent mechanisms. One striking example is glutamate, the brain's foremost excitatory neurotransmitter: since the 1990s, studies have consistently reported altered levels of glutamate in MDD, as well as antidepressant effects following molecular targeting of glutamatergic receptors. Therapeutically, this has led to advances in the discovery, testing, and clinical application of a wide array of glutamatergic agents, particularly ketamine. Notably, ketamine has been demonstrated to rapidly improve mood symptoms, unlike monoamine-based interventions, and the neurobiological basis behind this rapid antidepressant response is under active investigation. Advances in brain imaging techniques, including functional magnetic resonance imaging, magnetic resonance spectroscopy, and positron emission tomography, enable the identification of the brain network-based characteristics distinguishing rapid glutamatergic modulation from the effect of slow-acting conventional monoamine-based pharmacology. Here, we review brain imaging studies that examine brain connectivity features associated with rapid antidepressant response in MDD patients treated with glutamatergic pharmacotherapies in contrast with patients treated with slow-acting monoamine-based treatments. Trends in recent brain imaging literature suggest that the activity of brain regions is organized into coherent functionally distinct networks, termed intrinsic connectivity networks (ICNs). We provide an overview of major ICNs implicated in depression and explore how treatment response following glutamatergic modulation alters functional connectivity of limbic, cognitive, and executive nodes within ICNs, with well-characterized anti-anhedonic effects and the enhancement of “top-down” executive control. Alterations within and between the core ICNs could potentially exert downstream effects on the nodes within other brain networks of relevance to MDD that are structurally and functionally interconnected through glutamatergic synapses. Understanding similarities and differences in brain ICNs features underlying treatment response will positively impact the trajectory and outcomes for adults suffering from MDD and will facilitate the development of biomarkers to enable glutamate-based precision therapeutics. |
format | Online Article Text |
id | pubmed-9199367 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91993672022-06-16 Intrinsic Connectivity Networks of Glutamate-Mediated Antidepressant Response: A Neuroimaging Review Demchenko, Ilya Tassone, Vanessa K. Kennedy, Sidney H. Dunlop, Katharine Bhat, Venkat Front Psychiatry Psychiatry Conventional monoamine-based pharmacotherapy, considered the first-line treatment for major depressive disorder (MDD), has several challenges, including high rates of non-response. To address these challenges, preclinical and clinical studies have sought to characterize antidepressant response through monoamine-independent mechanisms. One striking example is glutamate, the brain's foremost excitatory neurotransmitter: since the 1990s, studies have consistently reported altered levels of glutamate in MDD, as well as antidepressant effects following molecular targeting of glutamatergic receptors. Therapeutically, this has led to advances in the discovery, testing, and clinical application of a wide array of glutamatergic agents, particularly ketamine. Notably, ketamine has been demonstrated to rapidly improve mood symptoms, unlike monoamine-based interventions, and the neurobiological basis behind this rapid antidepressant response is under active investigation. Advances in brain imaging techniques, including functional magnetic resonance imaging, magnetic resonance spectroscopy, and positron emission tomography, enable the identification of the brain network-based characteristics distinguishing rapid glutamatergic modulation from the effect of slow-acting conventional monoamine-based pharmacology. Here, we review brain imaging studies that examine brain connectivity features associated with rapid antidepressant response in MDD patients treated with glutamatergic pharmacotherapies in contrast with patients treated with slow-acting monoamine-based treatments. Trends in recent brain imaging literature suggest that the activity of brain regions is organized into coherent functionally distinct networks, termed intrinsic connectivity networks (ICNs). We provide an overview of major ICNs implicated in depression and explore how treatment response following glutamatergic modulation alters functional connectivity of limbic, cognitive, and executive nodes within ICNs, with well-characterized anti-anhedonic effects and the enhancement of “top-down” executive control. Alterations within and between the core ICNs could potentially exert downstream effects on the nodes within other brain networks of relevance to MDD that are structurally and functionally interconnected through glutamatergic synapses. Understanding similarities and differences in brain ICNs features underlying treatment response will positively impact the trajectory and outcomes for adults suffering from MDD and will facilitate the development of biomarkers to enable glutamate-based precision therapeutics. Frontiers Media S.A. 2022-05-26 /pmc/articles/PMC9199367/ /pubmed/35722550 http://dx.doi.org/10.3389/fpsyt.2022.864902 Text en Copyright © 2022 Demchenko, Tassone, Kennedy, Dunlop and Bhat. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Psychiatry Demchenko, Ilya Tassone, Vanessa K. Kennedy, Sidney H. Dunlop, Katharine Bhat, Venkat Intrinsic Connectivity Networks of Glutamate-Mediated Antidepressant Response: A Neuroimaging Review |
title | Intrinsic Connectivity Networks of Glutamate-Mediated Antidepressant Response: A Neuroimaging Review |
title_full | Intrinsic Connectivity Networks of Glutamate-Mediated Antidepressant Response: A Neuroimaging Review |
title_fullStr | Intrinsic Connectivity Networks of Glutamate-Mediated Antidepressant Response: A Neuroimaging Review |
title_full_unstemmed | Intrinsic Connectivity Networks of Glutamate-Mediated Antidepressant Response: A Neuroimaging Review |
title_short | Intrinsic Connectivity Networks of Glutamate-Mediated Antidepressant Response: A Neuroimaging Review |
title_sort | intrinsic connectivity networks of glutamate-mediated antidepressant response: a neuroimaging review |
topic | Psychiatry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9199367/ https://www.ncbi.nlm.nih.gov/pubmed/35722550 http://dx.doi.org/10.3389/fpsyt.2022.864902 |
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