Imaging studies of treatment-resistant depression (TRD) have examined brain activity, structure, and metabolite concentrations to identify critical areas of investigation and potential treatment targets. This chapter reviews findings from structural MRI, functional MRI, and magnetic resonance spectroscopy. Decreased connectivity and metabolite concentrations in frontal brain areas appear to characterize TRD, though results are not consistent across studies. Treatments including rapid-acting antidepressants and transcranial magnetic stimulation have shown some efficacy in reversing these changes while alleviating depressive symptoms. However, few TRD imaging studies exist, often with small sample sizes or varied methods, making firm conclusions difficult. Larger studies with unified hypotheses and data sharing could improve characterization of the illness and identify new treatment targets.
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.