Functional connectivity of the amygdala subregions and the antidepressant effects of repeated ketamine infusions in major depressive disorder.

Abnormal connectivity between a specific amygdala subregion (the left laterobasal amygdala) and the left precuneus in people with major depressive disorder is linked to how well ketamine treatment works. After six doses of ketamine (0.5 mg/kg), differences in connectivity changes between responders and nonresponders appeared in the bilateral centromedial amygdala with the left orbital part of the superior frontal gyrus and in the left laterobasal amygdala with the right middle frontal gyrus. A baseline difference in connectivity between the left laterobasal amygdala and the right superior/middle temporal gyrus predicted the antidepressant effect on Day 13, suggesting that ketamine may improve symptoms by regulating amygdala subregion networks.

Study at a glance

Abstract

Amygdala subregion-based network dysfunction has been determined to be centrally implicated in major depressive disorder (MDD). Little is known about whether ketamine modulates amygdala subarea-related networks. We aimed to investigate the relationships between changes in the resting-state functional connectivity (RSFC) of amygdala subregions and ketamine treatment and to identify important neuroimaging predictors of treatment outcomes. Thirty-nine MDD patients received six doses of ketamine (0.5 mg/kg). Depressive symptoms were assessed, and magnetic resonance imaging (MRI) scans were performed before and after treatment. Forty-five healthy controls underwent one MRI scan. Seed-to-voxel RSFC analyses were performed on the amygdala subregions, including the centromedial amygdala (CMA), laterobasal amygdala (LBA), and superficial amygdala subregions. Abnormal RSFC between the left LBA and the left precuneus in MDD patients is related to the therapeutic efficacy of ketamine. There were significant differences in changes in bilateral CMA RSFC with the left orbital part superior frontal gyrus and in changes in the left LBA with the right middle frontal gyrus between responders and nonresponders following ketamine treatment. Moreover, there was a difference in the RSFC of left LBA and the right superior temporal gyrus/middle temporal gyrus (STG/MTG) between responders and nonresponders at baseline, which could predict the antidepressant effect of ketamine on Day 13. The mechanism by which ketamine improves depressive symptoms may be related to its regulation of RSFC in the amygdala subregion. The RSFC between the left LBA and right STG/MTG may predict the response to the antidepressant effect of ketamine.