Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression

Summary & key facts

In a randomized trial, 98 adults with treatment-resistant depression had brain scans before and 24 hours after a single intravenous infusion of ketamine (0.5 mg/kg) or saline. The researchers measured mean diffusivity (DTI-MD), an MRI-based, indirect marker of microstructural brain change that tends to fall when new synapses or tissue density increase. They found that bigger decreases in DTI-MD over 24 hours were linked with larger improvements in depression scores in several brain regions, with some region-specific differences between the ketamine and saline groups. The results are consistent with the idea that rapid changes in the brain’s microstructure relate to symptom change, but the st

Key facts:

• 98 adults with unipolar, treatment-resistant depression had usable diffusion MRI data at both timepoints. Sixty-seven received ketamine (0.5 mg/kg); 31 received saline.
• Baseline depression severity was high: mean MADRS score was 32.81 (SD 5.39) in the analyzed sample. All participants had failed at least one antidepressant in the current episode.
• DTI mean diffusivity (DTI-MD) is an MRI measure of water diffusion in gray matter. Prior work links decreases in DTI-MD to increased microstructural density such as more synapses; in this study a decrease in DTI-MD from baseline to 24 hours
• Across several brain regions, individuals with larger decreases in DTI-MD from pre-infusion to 24 hours tended to show larger improvements in depression scores (MADRS and QIDS-SR). These relationships were reported as associations, not proo
• In left BA10 and left amygdala, the link between DTI-MD change and symptom improvement was driven mainly by the ketamine group (group × DTI-MD interaction p-values reported in the range 0.016–0.082).
• In right BA10, the association between DTI-MD change and depression improvement generalized to both ketamine and saline groups (p = 0.007).
• For the left and right hippocampus, the pattern differed on the MADRS: interaction effects indicated an inverse association in the ketamine arm (group × DTI-MD interaction p = 0.032–0.06), meaning the relationship ran in the opposite direct
• These analyses used a subset of the larger clinical trial (154 enrolled overall). Reasons for having 98 usable DTI datasets included that some participants were enrolled before the DTI scan was added and some scans were unusable due to scan

Topics

Advanced MRI Techniques and Applications Functional Brain Connectivity Studies Treatment of Major Depression

Categories

Cognitive Neuroscience Life Sciences Neuroscience

Tags

Amygdala Anesthesia Antidepressant Depression (economics) Diffusion MRI Economics Hippocampus Internal medicine Ketamine Macroeconomics Magnetic resonance imaging Major depressive disorder Medicine Neuroplasticity Neuroscience Psychology Radiology Randomized controlled trial