Default Mode Connectivity in Major Depressive Disorder Measured Up to 10 Days After Ketamine Administration

BACKGROUND: The symptoms of major depressive disorder (MDD) are rapidly alleviated by administration of a single dose of the glutamatergic modulator ketamine. However, few studies have investigated the potential sustained neural effects of this agent beyond immediate infusion. This study used functional magnetic resonance imaging to examine the effect of a single ketamine infusion on the resting state default mode network (DMN) at 2 and 10 days after a single ketamine infusion in unmedicated subjects with MDD as well as healthy control subjects (HCs). METHODS: Data were drawn from a double-blind, placebo-controlled crossover study of 58 participants (33 with MDD and 25 HCs) who received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 separate test days spaced 2 weeks apart. Eight minutes of functional magnetic resonance imaging resting state data was acquired at baseline and at about 2 and 10 days after both infusions. The DMN was defined using seed-based correlation and was compared across groups and scans. RESULTS: In subjects with MDD, connectivity between the insula and the DMN was normalized compared with HCs 2 days postketamine infusion. This change was reversed after 10 days and did not appear in either of the placebo scans. Group-specific connectivity differences in drug response were observed, most notably in the insula in subjects with MDD and in the thalamus in HCs. CONCLUSIONS: Connectivity changes in the insula in subjects with MDD suggest that ketamine may normalize the interaction between the DMN and salience networks, supporting the triple network dysfunction model of MDD.