Treatment-resistant depression affects 30-50% of people with major depressive disorder. Electroconvulsive therapy and ketamine can relieve it, but how they work is unclear. This transcriptome analysis of peripheral blood from 37 people receiving electroconvulsive therapy, 60 receiving ketamine, and 35 non-depressed controls found no longitudinal changes in gene expression for either treatment after correcting for multiple comparisons. In the ketamine group, one gene (IGKV1-9) differed between remitters and non-remitters at baseline. In the electroconvulsive therapy group, six co-regulated gene modules differed at baseline between patients and controls. Pre-treatment gene expression differences may have predictive value, but larger studies are needed.
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.