Regulation of neural responses to emotion perception by ketamine in individuals with treatment-resistant major depressive disorder

A single low dose of ketamine increases brain activity in the right caudate when people with treatment-resistant depression view happy faces, reversing a baseline deficit compared with healthy volunteers. Twenty patients with treatment-resistant depression not taking other antidepressants underwent fMRI before and 24 hours after receiving intravenous ketamine (0.5 mg per kg of body weight). Twenty matched healthy controls were scanned once. Before ketamine, depressed patients showed reduced neural responses to happy faces in the right caudate. After ketamine, responses to happy faces increased in a similar region. Greater connectivity of the right caudate during positive emotion perception was linked to greater improvement in depression severity. No effects were seen for sad faces.

Study at a glance

Abstract

The glutamate N-methyl-D-aspartate receptor antagonist ketamine has demonstrated antidepressant effects in individuals with treatment-resistant major depressive disorder (TRD) within 24 h of a single dose. The current study utilized functional magnetic resonance imaging (fMRI) and two separate emotion perception tasks to examine the neural effects of ketamine in patients with TRD. One task used happy and neutral facial expressions; the other used sad and neutral facial expressions. Twenty patients with TRD free of concomitant antidepressant medication underwent fMRI at baseline and 24 h following administration of a single intravenous dose of ketamine (0.5 mg kg(-1)). Adequate data were available for 18 patients for each task. Twenty age- and sex-matched healthy volunteers were scanned at one time point for baseline comparison. Whole-brain, voxel-wise analyses were conducted controlling for a family-wise error rate (FWE) of P<0.05. Compared with healthy volunteers, TRD patients showed reduced neural responses to positive faces within the right caudate. Following ketamine, neural responses to positive faces were selectively increased within a similar region of right caudate. Connectivity analyses showed that greater connectivity of the right caudate during positive emotion perception was associated with improvement in depression severity following ketamine. No main effect of group was observed for the sad faces task. Our results indicate that ketamine specifically enhances neural responses to positive emotion within the right caudate in depressed individuals in a pattern that appears to reverse baseline deficits and that connectivity of this region may be important for the antidepressant effects of ketamine.