Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, United States.
In people with treatment-resistant depression, a single low-dose ketamine infusion increased glutamate levels in the dorsal anterior cingulate cortex only in those who responded to treatment, and lower pre-treatment glutamate levels predicted greater improvement in depression scores. GABA levels did not change after treatment. Other brain metabolites linked to neuronal health and metabolism also increased. These findings suggest that ketamine's antidepressant effect involves sustained enhancement of glutamate-related neurotransmission and that baseline glutamate levels may help predict who will benefit from ketamine.
Ketamine treatment alters how brain networks dynamically interact in people with treatment-resistant depression. After four ketamine infusions over two weeks, patients spent less time in a visual-network brain state and more time in a central-executive-network state. Transitions between the salience network and central executive network increased, while salience-to-visual transitions decreased. Reduced time in the salience-network state was linked to less rumination. Before treatment, depressed patients differed from healthy controls in these same dynamic patterns, suggesting ketamine may shift network dynamics toward a healthier profile.