Hippocampal volume changes after (R,S)-ketamine administration in patients with major depressive disorder and healthy volunteers.
Jennifer W. Evans, Morgan C Graves, Allison C. Nugent, Carlos A. Zarate
Scientific Reports February 24, 2024 DOI: 10.1038/s41598-024-54370-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled, crossover trial Longitudinal Peer reviewed |
|---|---|
| Sample size | 56 |
| Population | Healthy volunteers and unmedicated individuals with treatment-resistant depression |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Duration | 40-minute IV infusion, scans at baseline, acute (1-2 days), and interim (9-10 days post-infusion) |
| Topics | Ketamine Depression Esketamine |
| Keywords | Depression treatment Brain imaging Amygdala |
| Citations | 9 |
| Key findings | At 10 days post-infusion, a slight increase in whole left amygdalar volume was observed in individuals with treatment-resistant depression after ketamine compared to placebo, with no other differences found between groups. |
Abstract
The hippocampus and amygdala have been implicated in the pathophysiology and treatment of major depressive disorder (MDD). Preclinical models suggest that stress-related changes in these regions can be reversed by antidepressants, including ketamine. Clinical studies have identified reduced volumes in MDD that are thought to be potentiated by early life stress and worsened by repeated depressive episodes. This study used 3T and 7T structural magnetic resonance imaging data to examine longitudinal changes in hippocampal and amygdalar subfield volumes associated with ketamine treatment. Data were drawn from a previous double-blind, placebo-controlled, crossover trial of healthy volunteers (HVs) unmedicated individuals with treatment-resistant depression (TRD) (3T: 18 HV, 26 TRD, 7T: 17 HV, 30 TRD) who were scanned at baseline and twice following either a 40 min IV ketamine (0.5 mg/kg) or saline infusion (acute: 1-2 days, interim: 9-10 days post infusion). No baseline differences were noted between the two groups. At 10 days post-infusion, a slight increase was observed between ketamine and placebo scans in whole left amygdalar volume in individuals with TRD. No other differences were found between individuals with TRD and HVs at either field strength. These findings shed light on the timing of ketamine's effects on cortical structures.
Comparable studies
Other randomized controlled trials on ketamine for depression, most cited first.
Citations in the library
Cited by 4
- Neural correlates of treatment response to ketamine for treatment-resistant depression: A systematic review of MRI-based studies. Psychiatry Research October 1, 2024
- Towards an expanded neurocognitive account of ketamine's rapid antidepressant effects. The International Journal of Neuropsychopharmacology February 4, 2025
- Acute effects of intranasal esketamine application on thalamic structures in healthy individuals. The International Journal of Neuropsychopharmacology June 6, 2025
- The hippocampus as a central hub in ketamine's antidepressant action: from molecules to circuit rewiring. Neuropsychopharmacology February 1, 2026
Cites 6
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Ketamine Has Distinct Electrophysiological and Behavioral Effects in Depressed and Healthy Subjects Molecular Psychiatry February 27, 2018
- Ketamine Rapidly Enhances Glutamate-Evoked Dendritic Spinogenesis in Medial Prefrontal Cortex Through Dopaminergic Mechanisms. Biological Psychiatry January 8, 2021
- Ketamine administration reduces amygdalo‐hippocampal reactivity to emotional stimulation Human Brain Mapping February 25, 2016
- Who is blind in psychedelic research? Letter to the editor regarding: blinding and expectancy confounds in psychedelic randomized controlled trials Expert Review of Clinical Pharmacology July 6, 2021
and 1 more in the library