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 infusions alter brain connectivity in people with major depressive disorder, particularly in circuits involving the habenula and nucleus accumbens, which are linked to reward processing. After four infusions, changes in functional connections between these regions and visual, parietal, and cerebellar areas correlated with improvements in mood and anhedonia. For example, decreased variability in connectivity between the left habenula and right precuneus/visual cortex was associated with better mood, while altered connectivity between the left habenula and visual/parietal cortices and between the left nucleus accumbens and visual/parietal cortices correlated with reduced anhedonia. No such changes occurred in healthy controls.