Ketamine effects on resting state functional brain connectivity in major depressive disorder patients: a hypothesis-driven analysis based on a network model of depression.
Frontiers in neuroscience January 1, 2025 Kasper Recourt, Joop Van Gerven, Nadieh Drenth et al. 1 citation
Ketamine, given intravenously at 0.5 mg/kg, rapidly reduces depression symptoms in patients with non-treatment-resistant major depressive disorder. In a randomized, double-blind, placebo-controlled crossover study with 16 patients, ketamine lowered mean MADRS scores from 21.2 before dosing to 10.3 at 24 hours, compared with placebo. Resting-state fMRI showed that ketamine altered functional connectivity only in brain circuits previously linked to depression—the corticolimbic-insular-striatal-pallidal-thalamic (CLIPST) network—at both acute (50–165 minutes) and delayed (24 hours) time points. No connectivity changes occurred outside this depression-related circuitry. The results indicate that ketamine specifically targets depression-associated neural pathways, supporting model-based analysis in future pharmaco-fMRI studies.