Hippocampal volume changes after (R,S)-ketamine administration in patients with major depressive disorder and healthy volunteers.

The hippocampus and amygdala are brain regions involved in major depressive disorder (MDD) and its treatment. Preclinical work suggests antidepressants, including ketamine, can reverse stress-related changes in these areas. Clinical studies show reduced volumes in MDD, worsened by early life stress and repeated episodes. This analysis of structural MRI data from a prior double-blind, placebo-controlled, crossover trial examined changes in hippocampal and amygdalar subfield volumes after ketamine treatment. Participants included healthy volunteers and unmedicated individuals with treatment-resistant depression scanned at baseline and twice after a single ketamine or saline infusion. At 10 days post-infusion, a slight increase in whole left amygdalar volume was observed in the ketamine group among those with depression. No other differences were found between groups at either 3T or 7T field strength.

Study at a glance

Abstract

The hippocampus and amygdala have been implicated in the pathophysiology and treatment of major depressive disorder (MDD). Preclinical models suggest that stress-related changes in these regions can be reversed by antidepressants, including ketamine. Clinical studies have identified reduced volumes in MDD that are thought to be potentiated by early life stress and worsened by repeated depressive episodes. This study used 3T and 7T structural magnetic resonance imaging data to examine longitudinal changes in hippocampal and amygdalar subfield volumes associated with ketamine treatment. Data were drawn from a previous double-blind, placebo-controlled, crossover trial of healthy volunteers (HVs) unmedicated individuals with treatment-resistant depression (TRD) (3T: 18 HV, 26 TRD, 7T: 17 HV, 30 TRD) who were scanned at baseline and twice following either a 40 min IV ketamine (0.5 mg/kg) or saline infusion (acute: 1-2 days, interim: 9-10 days post infusion). No baseline differences were noted between the two groups. At 10 days post-infusion, a slight increase was observed between ketamine and placebo scans in whole left amygdalar volume in individuals with TRD. No other differences were found between individuals with TRD and HVs at either field strength. These findings shed light on the timing of ketamine's effects on cortical structures.