Ketamine Normalizes the Structural Alterations of Inferior Frontal Gyrus in Depression
Open accessAbstract
Background: Ketamine is a novel fast-acting antidepressant. Acute ketamine treatment can reverse microstructure deficits and normalize functional alterations in the brain, but little is known about the impacts of ketamine on brain volumes in individuals with depression. Methods: We used 3 T magnetic resonance imaging (MRI) and tensorbased morphological methods to investigate the regional volume differences for 29 healthy control (HC) subjects and 21 subjects with major depressive disorder (MDD), including 10 subjects with comorbid post-traumatic stress disorder (PTSD). All the subjects participated in MRI scanning before and 24 h post intravenous ketamine infusion. The effects of acute ketamine administration on HC, MDD, and MDD/PTSD groups were examined separately by whole-brain voxel-wise t-tests. Results: Our data showed smaller volume of inferior frontal gyrus (IFG, opercular part) in MDD and MDD/PTSD subjects compared to HC, and a significant correlation between opercular IFG volume and depressive severity in MDD subjects only. Ketamine administration normalized the structural alterations of opercular IFG in both MDD and MDD/PTSD groups, and significantly improved depressive and PTSD symptoms. Twenty-four hours after a single ketamine infusion, there were two clusters of voxels with volume changes in MDD subjects, including significantly increased volumes of opercular IFG. No significant structural alterations were found in the MDD/PTSD or HC groups. Conclusion: These findings provide direct evidence that acute ketamine administration can normalize structural alterations associated with depression and highlight the importance of IFG in the guidance of future therapeutic targets.
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Ketamine treatment rescues atrophy of the inferior frontal gyrus observed in MDD and PTSD patients.
“ketamine treatment has been shown to rescue atrophy of the inferior frontal gyrus observed in MDD and PTSD patients (120)”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [120]
The Conclusion reports lower inferior frontal gyrus volume in the MDD and MDD/PTSD groups and normalization of right opercular IFG volume after ketamine. But the Results (Volume Differences Compared to HC) found no significant volume change within the MDD/PTSD group, and the study included patients with PTSD only when it was comorbid with MDD. Thus, the claim overstates the evidence if it implies a demonstrated reversal of atrophy in PTSD patients generally. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThere is some evidence in humans that psychoplastogens can impact brain structure.
“There is some evidence in humans that psychoplastogens can impact brain structure as well.”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [120]
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The Role of Rapid-Acting Antidepressants in Suicidal Crisis Management
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Do Molecular Interventions (Ketamine) Re-establish Synapses in Affected Brain Structures?
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Restoring Grey Matter Through Treatment
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- Authors
- Dai, D., Lacadie, C. M., Holmes, S. E., Cool, R., Anticevic, A., Averill, C., Abdallah, C., & Esterlis, I.
- Affiliations
- Yale University (US)
- Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
- Michael E. DeBakey VA Medical Center (US)
- United States Department of Veterans Affairs (US)
- Corresponding author
- Esterlis, Irina
- ORCID
- Venue
- Chronic Stress
- Publisher
- SAGE Publications
- Published
- 2020-01
- Volume
- 4
- Pages
- 2470547020980681-2470547020980681
- ISSN
- 2470-5470 (ISSN-L)
- PMC
- PMC7758564
- OpenAlex
- W3115496309
- Cited by
- 34
- References
- 58
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 8 · 2021: 3
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Chronic Stress (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- ketamine, major depressive disorder, post-traumatic stress disorder, inferior frontal gyrus, brain volume, rapid-acting antidepressants, depression severity, brain structural changes
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