Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action.
Increasing preclinical and clinical evidence underscores the strong and rapid antidepressant properties of the glutamate-modulating NMDA receptor antagonist ketamine. Targeting the glutamatergic system might thus provide a novel molecular strategy for antidepressant treatment. Since glutamate is the...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3461985?pdf=render |
| _version_ | 1818956271201550336 |
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| author | Milan Scheidegger Martin Walter Mick Lehmann Coraline Metzger Simone Grimm Heinz Boeker Peter Boesiger Anke Henning Erich Seifritz |
| author_facet | Milan Scheidegger Martin Walter Mick Lehmann Coraline Metzger Simone Grimm Heinz Boeker Peter Boesiger Anke Henning Erich Seifritz |
| author_sort | Milan Scheidegger |
| collection | DOAJ |
| description | Increasing preclinical and clinical evidence underscores the strong and rapid antidepressant properties of the glutamate-modulating NMDA receptor antagonist ketamine. Targeting the glutamatergic system might thus provide a novel molecular strategy for antidepressant treatment. Since glutamate is the most abundant and major excitatory neurotransmitter in the brain, pathophysiological changes in glutamatergic signaling are likely to affect neurobehavioral plasticity, information processing and large-scale changes in functional brain connectivity underlying certain symptoms of major depressive disorder. Using resting state functional magnetic resonance imaging (rsfMRI), the "dorsal nexus "(DN) was recently identified as a bilateral dorsal medial prefrontal cortex region showing dramatically increased depression-associated functional connectivity with large portions of a cognitive control network (CCN), the default mode network (DMN), and a rostral affective network (AN). Hence, Sheline and colleagues (2010) proposed that reducing increased connectivity of the DN might play a critical role in reducing depression symptomatology and thus represent a potential therapy target for affective disorders. Here, using a randomized, placebo-controlled, double-blind, crossover rsfMRI challenge in healthy subjects we demonstrate that ketamine decreases functional connectivity of the DMN to the DN and to the pregenual anterior cingulate (PACC) and medioprefrontal cortex (MPFC) via its representative hub, the posterior cingulate cortex (PCC). These findings in healthy subjects may serve as a model to elucidate potential biomechanisms that are addressed by successful treatment of major depression. This notion is further supported by the temporal overlap of our observation of subacute functional network modulation after 24 hours with the peak of efficacy following an intravenous ketamine administration in treatment-resistant depression. |
| first_indexed | 2024-12-20T10:51:18Z |
| format | Article |
| id | doaj.art-096314e374d342f1b21dedae414b5ab3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T10:51:18Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-096314e374d342f1b21dedae414b5ab32022-12-21T19:43:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4479910.1371/journal.pone.0044799Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action.Milan ScheideggerMartin WalterMick LehmannCoraline MetzgerSimone GrimmHeinz BoekerPeter BoesigerAnke HenningErich SeifritzIncreasing preclinical and clinical evidence underscores the strong and rapid antidepressant properties of the glutamate-modulating NMDA receptor antagonist ketamine. Targeting the glutamatergic system might thus provide a novel molecular strategy for antidepressant treatment. Since glutamate is the most abundant and major excitatory neurotransmitter in the brain, pathophysiological changes in glutamatergic signaling are likely to affect neurobehavioral plasticity, information processing and large-scale changes in functional brain connectivity underlying certain symptoms of major depressive disorder. Using resting state functional magnetic resonance imaging (rsfMRI), the "dorsal nexus "(DN) was recently identified as a bilateral dorsal medial prefrontal cortex region showing dramatically increased depression-associated functional connectivity with large portions of a cognitive control network (CCN), the default mode network (DMN), and a rostral affective network (AN). Hence, Sheline and colleagues (2010) proposed that reducing increased connectivity of the DN might play a critical role in reducing depression symptomatology and thus represent a potential therapy target for affective disorders. Here, using a randomized, placebo-controlled, double-blind, crossover rsfMRI challenge in healthy subjects we demonstrate that ketamine decreases functional connectivity of the DMN to the DN and to the pregenual anterior cingulate (PACC) and medioprefrontal cortex (MPFC) via its representative hub, the posterior cingulate cortex (PCC). These findings in healthy subjects may serve as a model to elucidate potential biomechanisms that are addressed by successful treatment of major depression. This notion is further supported by the temporal overlap of our observation of subacute functional network modulation after 24 hours with the peak of efficacy following an intravenous ketamine administration in treatment-resistant depression.http://europepmc.org/articles/PMC3461985?pdf=render |
| spellingShingle | Milan Scheidegger Martin Walter Mick Lehmann Coraline Metzger Simone Grimm Heinz Boeker Peter Boesiger Anke Henning Erich Seifritz Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action. PLoS ONE |
| title | Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action. |
| title_full | Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action. |
| title_fullStr | Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action. |
| title_full_unstemmed | Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action. |
| title_short | Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action. |
| title_sort | ketamine decreases resting state functional network connectivity in healthy subjects implications for antidepressant drug action |
| url | http://europepmc.org/articles/PMC3461985?pdf=render |
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