In patients with major depressive disorder, differences in brain white matter structure before ketamine treatment may predict who will respond to the drug 24 hours later. Using diffusion imaging in 10 patients, those who showed more than 50% symptom improvement had greater fractional anisotropy in the cingulum and forceps minor pathways compared to non-responders. Non-responders also had lower fractional anisotropy and higher radial and mean diffusivity in these pathways compared to healthy controls, and they had an earlier age of depression onset and longer current episode. These preliminary findings suggest that the structural integrity of emotion-related brain networks may influence ketamine's antidepressant effect.
Ketamine produces rapid antidepressant effects even in people with treatment-resistant depression, but how it alters brain function is not fully understood. In this study, 47 patients with treatment-resistant depression and 32 healthy controls performed a brain-imaging task measuring response inhibition. After one and then four intravenous ketamine infusions, 37 patients repeated the task. Brain activation decreased in regions involved in inhibitory control, including prefrontal and parietal areas and visual cortex, following repeated treatment. Patients who achieved remission had lower activation in the supplementary motor area before treatment, which then normalized toward control levels after ketamine. These changes in the supplementary motor area during response inhibition were linked to reduced depressive symptoms and may predict treatment outcome.