Glutamatergic Signaling Drives Ketamine-Mediated Response in Depression: Evidence from Dynamic Causal Modeling
The International Journal of Neuropsychopharmacology April 10, 2018 Jessica R. Gilbert, Julia S. Yarrington, Kathleen E. Wills et al. 58 citations
Ketamine, a drug that modulates glutamate signaling, produces rapid antidepressant effects. In a double-blind, crossover, placebo-controlled study, 18 people with major depressive disorder and 18 healthy controls each received a single intravenous infusion of ketamine (0.5 mg/kg) and a saline placebo. Magnetoencephalography measured brain activity during tactile stimulation 6 to 9 hours after each infusion. Dynamic causal modeling revealed that ketamine altered NMDA receptor-mediated connectivity differently in the two groups: backward connections were enhanced in depressed subjects, while forward connections were enhanced in controls. Among depressed subjects, improved mood correlated with reduced NMDA and AMPA connectivity in the somatosensory network. The findings indicate that AMPA- and NMDA-mediated glutamatergic signaling is central to ketamine's antidepressant action.