Preliminary evidence that ketamine alters anterior cingulate resting-state functional connectivity in depressed individuals
Abstract Activity changes within the anterior cingulate cortex (ACC) are implicated in the antidepressant effects of ketamine, but the ACC is cytoarchitectonically and functionally heterogeneous and ketamine’s effects may be subregion specific. In the context of a double-blind randomized placebo-con...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-12-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02674-1 |
| _version_ | 1797413933445808128 |
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| author | Laith Alexander Peter C. T. Hawkins Jennifer W. Evans Mitul A. Mehta Carlos A. Zarate |
| author_facet | Laith Alexander Peter C. T. Hawkins Jennifer W. Evans Mitul A. Mehta Carlos A. Zarate |
| author_sort | Laith Alexander |
| collection | DOAJ |
| description | Abstract Activity changes within the anterior cingulate cortex (ACC) are implicated in the antidepressant effects of ketamine, but the ACC is cytoarchitectonically and functionally heterogeneous and ketamine’s effects may be subregion specific. In the context of a double-blind randomized placebo-controlled crossover trial investigating the clinical and resting-state fMRI effects of intravenous ketamine vs. placebo in patients with treatment resistant depression (TRD) vs. healthy volunteers (HV), we used seed-based resting-state functional connectivity (rsFC) analyses to determine differential changes in subgenual ACC (sgACC), perigenual ACC (pgACC) and dorsal ACC (dACC) rsFC two days post-infusion. Across cingulate subregions, ketamine differentially modulated rsFC to the right insula and anterior ventromedial prefrontal cortex, compared to placebo, in TRD vs. HV; changes to pgACC-insula connectivity correlated with improvements in depression scores. Post-hoc analysis of each cingulate subregion separately revealed differential modulation of sgACC-hippocampal, sgACC-vmPFC, pgACC-posterior cingulate, and dACC-supramarginal gyrus connectivity. By comparing rsFC changes following ketamine vs. placebo in the TRD group alone, we found that sgACC rsFC was most substantially modulated by ketamine vs. placebo. Changes to sgACC-pgACC, sgACC-ventral striatal, and sgACC-dACC connectivity correlated with improvements in anhedonia symptoms. This preliminary evidence suggests that accurate segmentation of the ACC is needed to understand the precise effects of ketamine’s antidepressant and anti-anhedonic action. |
| first_indexed | 2024-03-09T05:24:53Z |
| format | Article |
| id | doaj.art-02b4f30b2c2345608942b4bf7b9ba630 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-03-09T05:24:53Z |
| publishDate | 2023-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-02b4f30b2c2345608942b4bf7b9ba6302023-12-03T12:37:12ZengNature Publishing GroupTranslational Psychiatry2158-31882023-12-0113111010.1038/s41398-023-02674-1Preliminary evidence that ketamine alters anterior cingulate resting-state functional connectivity in depressed individualsLaith Alexander0Peter C. T. Hawkins1Jennifer W. Evans2Mitul A. Mehta3Carlos A. Zarate4Institute of Psychiatry, Psychology and Neuroscience, King’s College London & Centre for Neuroimaging Sciences, King’s College LondonInstitute of Psychiatry, Psychology and Neuroscience, King’s College London & Centre for Neuroimaging Sciences, King’s College LondonExperimental Therapeutics and Pathophysiology Branch, National Institute of Mental HealthInstitute of Psychiatry, Psychology and Neuroscience, King’s College London & Centre for Neuroimaging Sciences, King’s College LondonExperimental Therapeutics and Pathophysiology Branch, National Institute of Mental HealthAbstract Activity changes within the anterior cingulate cortex (ACC) are implicated in the antidepressant effects of ketamine, but the ACC is cytoarchitectonically and functionally heterogeneous and ketamine’s effects may be subregion specific. In the context of a double-blind randomized placebo-controlled crossover trial investigating the clinical and resting-state fMRI effects of intravenous ketamine vs. placebo in patients with treatment resistant depression (TRD) vs. healthy volunteers (HV), we used seed-based resting-state functional connectivity (rsFC) analyses to determine differential changes in subgenual ACC (sgACC), perigenual ACC (pgACC) and dorsal ACC (dACC) rsFC two days post-infusion. Across cingulate subregions, ketamine differentially modulated rsFC to the right insula and anterior ventromedial prefrontal cortex, compared to placebo, in TRD vs. HV; changes to pgACC-insula connectivity correlated with improvements in depression scores. Post-hoc analysis of each cingulate subregion separately revealed differential modulation of sgACC-hippocampal, sgACC-vmPFC, pgACC-posterior cingulate, and dACC-supramarginal gyrus connectivity. By comparing rsFC changes following ketamine vs. placebo in the TRD group alone, we found that sgACC rsFC was most substantially modulated by ketamine vs. placebo. Changes to sgACC-pgACC, sgACC-ventral striatal, and sgACC-dACC connectivity correlated with improvements in anhedonia symptoms. This preliminary evidence suggests that accurate segmentation of the ACC is needed to understand the precise effects of ketamine’s antidepressant and anti-anhedonic action.https://doi.org/10.1038/s41398-023-02674-1 |
| spellingShingle | Laith Alexander Peter C. T. Hawkins Jennifer W. Evans Mitul A. Mehta Carlos A. Zarate Preliminary evidence that ketamine alters anterior cingulate resting-state functional connectivity in depressed individuals Translational Psychiatry |
| title | Preliminary evidence that ketamine alters anterior cingulate resting-state functional connectivity in depressed individuals |
| title_full | Preliminary evidence that ketamine alters anterior cingulate resting-state functional connectivity in depressed individuals |
| title_fullStr | Preliminary evidence that ketamine alters anterior cingulate resting-state functional connectivity in depressed individuals |
| title_full_unstemmed | Preliminary evidence that ketamine alters anterior cingulate resting-state functional connectivity in depressed individuals |
| title_short | Preliminary evidence that ketamine alters anterior cingulate resting-state functional connectivity in depressed individuals |
| title_sort | preliminary evidence that ketamine alters anterior cingulate resting state functional connectivity in depressed individuals |
| url | https://doi.org/10.1038/s41398-023-02674-1 |
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