Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression
Abstract Intravenous ketamine is posited to rapidly reverse depression by rapidly enhancing neuroplasticity. In human patients, we quantified gray matter microstructural changes on a rapid (24-h) timescale within key regions where neuroplasticity enhancements post-ketamine have been implicated in an...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-05-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02451-0 |
| _version_ | 1797827329662124032 |
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| author | Jared Kopelman Timothy A. Keller Benjamin Panny Angela Griffo Michelle Degutis Crystal Spotts Nicolas Cruz Elizabeth Bell Kevin Do-Nguyen Meredith L. Wallace Sanjay J. Mathew Robert H. Howland Rebecca B. Price |
| author_facet | Jared Kopelman Timothy A. Keller Benjamin Panny Angela Griffo Michelle Degutis Crystal Spotts Nicolas Cruz Elizabeth Bell Kevin Do-Nguyen Meredith L. Wallace Sanjay J. Mathew Robert H. Howland Rebecca B. Price |
| author_sort | Jared Kopelman |
| collection | DOAJ |
| description | Abstract Intravenous ketamine is posited to rapidly reverse depression by rapidly enhancing neuroplasticity. In human patients, we quantified gray matter microstructural changes on a rapid (24-h) timescale within key regions where neuroplasticity enhancements post-ketamine have been implicated in animal models. In this study, 98 unipolar depressed adults who failed at least one antidepressant medication were randomized 2:1 to a single infusion of intravenous ketamine (0.5 mg/kg) or vehicle (saline) and completed diffusion tensor imaging (DTI) assessments at pre-infusion baseline and 24-h post-infusion. DTI mean diffusivity (DTI-MD), a putative marker of microstructural neuroplasticity in gray matter, was calculated for 7 regions of interest (left and right BA10, amygdala, and hippocampus; and ventral Anterior Cingulate Cortex) and compared to clinical response measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptoms-Self-Report (QIDS-SR). Individual differences in DTI-MD change (greater decrease from baseline to 24-h post-infusion, indicative of more neuroplasticity enhancement) were associated with larger improvements in depression scores across several regions. In the left BA10 and left amygdala, these relationships were driven primarily by the ketamine group (group * DTI-MD interaction effects: p = 0.016–0.082). In the right BA10, these associations generalized to both infusion arms (p = 0.007). In the left and right hippocampus, on the MADRS only, interaction effects were observed in the opposite direction, such that DTI-MD change was inversely associated with depression change in the ketamine arm specifically (group * DTI-MD interaction effects: p = 0.032–0.06). The acute effects of ketamine on depression may be mediated, in part, by acute changes in neuroplasticity quantifiable with DTI. |
| first_indexed | 2024-04-09T12:46:15Z |
| format | Article |
| id | doaj.art-75a96ee47abf4bd6bca4f81ec2299f6e |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-09T12:46:15Z |
| publishDate | 2023-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-75a96ee47abf4bd6bca4f81ec2299f6e2023-05-14T11:28:39ZengNature Publishing GroupTranslational Psychiatry2158-31882023-05-011311910.1038/s41398-023-02451-0Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depressionJared Kopelman0Timothy A. Keller1Benjamin Panny2Angela Griffo3Michelle Degutis4Crystal Spotts5Nicolas Cruz6Elizabeth Bell7Kevin Do-Nguyen8Meredith L. Wallace9Sanjay J. Mathew10Robert H. Howland11Rebecca B. Price12University of California San Diego School of MedicineCarnegie Mellon UniversityUniversity of Pittsburgh School of MedicineUniversity of Pittsburgh School of MedicineUniversity of Pittsburgh School of MedicineUniversity of Pittsburgh School of MedicineUniversity of Pittsburgh School of MedicineUniversity of Pittsburgh School of MedicineUniversity of Pittsburgh School of MedicineUniversity of Pittsburgh School of MedicineBaylor College of Medicine and Michael E. DeBakey VA Medical CenterUniversity of Pittsburgh School of MedicineUniversity of Pittsburgh School of MedicineAbstract Intravenous ketamine is posited to rapidly reverse depression by rapidly enhancing neuroplasticity. In human patients, we quantified gray matter microstructural changes on a rapid (24-h) timescale within key regions where neuroplasticity enhancements post-ketamine have been implicated in animal models. In this study, 98 unipolar depressed adults who failed at least one antidepressant medication were randomized 2:1 to a single infusion of intravenous ketamine (0.5 mg/kg) or vehicle (saline) and completed diffusion tensor imaging (DTI) assessments at pre-infusion baseline and 24-h post-infusion. DTI mean diffusivity (DTI-MD), a putative marker of microstructural neuroplasticity in gray matter, was calculated for 7 regions of interest (left and right BA10, amygdala, and hippocampus; and ventral Anterior Cingulate Cortex) and compared to clinical response measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptoms-Self-Report (QIDS-SR). Individual differences in DTI-MD change (greater decrease from baseline to 24-h post-infusion, indicative of more neuroplasticity enhancement) were associated with larger improvements in depression scores across several regions. In the left BA10 and left amygdala, these relationships were driven primarily by the ketamine group (group * DTI-MD interaction effects: p = 0.016–0.082). In the right BA10, these associations generalized to both infusion arms (p = 0.007). In the left and right hippocampus, on the MADRS only, interaction effects were observed in the opposite direction, such that DTI-MD change was inversely associated with depression change in the ketamine arm specifically (group * DTI-MD interaction effects: p = 0.032–0.06). The acute effects of ketamine on depression may be mediated, in part, by acute changes in neuroplasticity quantifiable with DTI.https://doi.org/10.1038/s41398-023-02451-0 |
| spellingShingle | Jared Kopelman Timothy A. Keller Benjamin Panny Angela Griffo Michelle Degutis Crystal Spotts Nicolas Cruz Elizabeth Bell Kevin Do-Nguyen Meredith L. Wallace Sanjay J. Mathew Robert H. Howland Rebecca B. Price Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression Translational Psychiatry |
| title | Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression |
| title_full | Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression |
| title_fullStr | Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression |
| title_full_unstemmed | Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression |
| title_short | Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression |
| title_sort | rapid neuroplasticity changes and response to intravenous ketamine a randomized controlled trial in treatment resistant depression |
| url | https://doi.org/10.1038/s41398-023-02451-0 |
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