Volumetric changes in subcortical structures following repeated ketamine treatment in patients with major depressive disorder: a longitudinal analysis

Transl Psychiatry. 2020 Aug 3;10(1):264. doi: 10.1038/s41398-020-00945-9.


Abnormal subcortical structures have been associated with major depressive disorder (MDD) and could be reversed by antidepressant treatment. To date no study has examined the relationship between subcortical volumes and repeated ketamine treatment. The current study investigated volume changes in specific subcortical structures and hippocampal subfields after six ketamine infusions. Forty-four patients with MDD received six subanesthetic dose infusions of ketamine. Depressive symptoms were assessed and magnetic resonance imaging scans were performed before and after six ketamine infusions. FreeSurfer software was used to process the T1 images and analyze the volumes of the subcortical regions and hippocampal subfields. After six ketamine infusions, increases were observed in the volumes of the left amygdala; the right hippocampus; the cornu ammonis 4 body, granule cell and molecular layer of the dentate gyrus body in the left hippocampus; and the cornu ammonis 4 head and molecular layer head in the right hippocampus. Positive correlations were found between symptom improvement and the pretreatment volumes of the right thalamus (r = 0.501; P = 0.001) and left subiculum head of the hippocampus (r = 0.471; P = 0.002), and changes in the volumes of the left amygdala (r = -0.452; P = 0.003) and the left cornu ammonis 4 body (r = -0.537; P < 0.001). Our findings provided evidence for critical roles of the amygdala and specific hippocampal subfields in the antidepressant effect of repeated ketamine treatment. Relatively larger volumes in right thalamus and left subiculum head in the hippocampus can predict a superior clinical outcome of ketamine treatment in MDD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / diagnostic imaging
  • Antidepressive Agents / therapeutic use
  • Depressive Disorder, Major* / diagnostic imaging
  • Depressive Disorder, Major* / drug therapy
  • Hippocampus / diagnostic imaging
  • Humans
  • Ketamine* / therapeutic use
  • Magnetic Resonance Imaging
  • Organ Size


  • Antidepressive Agents
  • Ketamine