Antidepressant and antisuicidal effects of ketamine on the functional connectivity of prefrontal cortex-related circuits in treatment-resistant depression: A double-blind, placebo-controlled, randomized, longitudinal resting fMRI study.

A subanesthetic dose of ketamine alters functional connectivity in prefrontal cortex circuits of patients with treatment-resistant depression. Forty-eight patients were randomly assigned to receive a standard dose (0.5 mg/kg), a low dose (0.2 mg/kg), or a placebo infusion. The standard dose reduced connectivity between the left dorsal anterior cingulate cortex and right dorsolateral prefrontal cortex with other frontal regions; the low dose produced more widespread reductions in connectivity. Changes in suicidal ideation correlated with connectivity changes in opposite directions depending on dose. The findings suggest that modulation of prefrontal circuits underlies ketamine's antidepressant and antisuicidal effects.

Study at a glance

Abstract

Increasing evidence suggests that infusion of a subanesthetic dose of ketamine exerts antidepressant and antisuicidal effects in patients with treatment-resistant depression (TRD). In this investigation, we used the resting functional connectivity magnetic resonance imaging (fcMRI) to determine the effects of ketamine on the functional connectivity (FC) of prefrontal cortex (PFC)-related circuits in patients with TRD. Forty-eight patients with TRD were recruited and randomly divided into three groups on the basis of ketamine infusion dose: 0.5 mg/kg (standard dose), 0.2 mg/kg (low dose), or normal saline (a placebo infusion). Resting functional MRI data and clinical data were recorded at the baseline and on the third day after ketamine infusion treatment. The standard-dose group showed a reduction in the FC of the left dorsal anterior cingulate cortex (dACC) and right dorsolateral (dl)PFC with the other frontal regions. The low-dose group demonstrated a more pervasive reduction of FC in the bilateral dACC with other frontal and parietal regions. A negative correlation was observed between the reduction in suicidal ideation and the reduction in the FC between the left dACC and right ACC regions in the standard-dose group, whereas a positive correlation was observed between the reduction in suicidal ideation and the increase in the FC between the right dlPFC and left superior parietal region in the low-dose group. Our results support the hypothesis that PFC-related circuit modulation is crucial to the antidepressant and antisuicidal effects of the ketamine infusion treatment.