This randomized controlled trial investigated the relationship between rapid neuroplasticity changes and response to intravenous ketamine in 98 adults with treatment-resistant depression. Participants received either ketamine (0.5 mg/kg) or saline. Diffusion tensor imaging (DTI) assessed gray matter microstructural changes at baseline and 24 hours post-infusion. Results showed that individual differences in DTI mean diffusivity (MD) change were associated with improvements in depression scores. In the left BA10 and left amygdala, this relationship was primarily driven by the ketamine group. In the right BA10, the association held for both groups. Conversely, in the hippocampus, increased MD was associated with improved MADRS scores in the ketamine group. These findings suggest that ketamine's antidepressant effects may be mediated by acute neuroplasticity changes.

Jared Kopelman, Timothy A. Keller, Benjamin Panny, Angela Griffo, Michelle Degutis, Crystal Spott, Nicolas Cruz, Elizabeth Bell, Kevin Do-Young, Meredith L. Wallace, Sanjay J. Mathew, Robert H. Howland, Rebecca B. Price