Gray matter volume of rostral anterior cingulate cortex predicts rapid antidepressant response to ketamine

Eur Neuropsychopharmacol. 2021 Feb;43:63-70. doi: 10.1016/j.euroneuro.2020.11.017. Epub 2020 Dec 11.


Ketamine was recently approved for treatment resistant depression. However, despite its therapeutic potential, about 50% of patients do not show improvement under this therapy. In this prospective two-site study, we investigated baseline brain structural predictors for rapid symptom improvement after a single subanesthetic ketamine infusion. Furthermore, given the preclinical evidence and findings from a pilot study in a clinical population that ketamine induces rapid neuroplasticity, we performed an exploratory investigation of macroscopic changes 24 h post-treatment. T1-weighted MRI brain images from 33 depressed patients were acquired before and 24 h after a single ketamine infusion and analyzed using voxel-based morphometry (VBM). Additionally, we performed a region of interest (ROI)-based analysis of structures that have previously been shown to play a role in the antidepressant effects of ketamine: bilateral hippocampus, nucleus accumbens, anterior cingulate cortex, and thalamus. A whole-brain regression analysis showed that greater baseline volume of the bilateral rostral anterior cingulate cortex (rACC) significantly predicts rapid symptom reduction. The right ACC showed the same association in the ROI analysis, while the other regions yielded no significant results. Exploratory follow-up analyses revealed no volumetric changes 24 h after treatment. This is the first study reporting an association between pretreatment gray matter volume of the bilateral rACC and the rapid antidepressant effects of ketamine. Results are in line with previous investigations, which highlighted the potential of the rACC as a biomarker for response prediction to different antidepressant treatments. Ketamine-induced volumetric changes may be seen at later time points.

Trial registration: NCT02099630 NCT03609190.

Keywords: Anterior cingulate cortex; Gray matter volume; Ketamine; Major depression; Neuroplasticity; VBM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / pharmacology
  • Gray Matter / diagnostic imaging
  • Gyrus Cinguli / diagnostic imaging
  • Humans
  • Ketamine* / pharmacology
  • Magnetic Resonance Imaging
  • Pilot Projects
  • Prospective Studies


  • Antidepressive Agents
  • Ketamine

Associated data