Functional connectivity between prefrontal cortex and subgenual cingulate predicts antidepressant effects of ketamine

Eur Neuropsychopharmacol. 2019 Apr;29(4):501-508. doi: 10.1016/j.euroneuro.2019.02.008. Epub 2019 Feb 26.


Converging evidence suggests that a single sub-anesthetic dose of ketamine can produce strong and rapid antidepressant effects in patients that do not respond to standard treatment. Despite a considerable amount of research investigating ketamine's mechanisms of action, the exact neuronal targets conveying the antidepressant effects have not been identified yet. Preclinical studies suggest that molecular changes induced by ketamine bring forward large-scale network reconfigurations that might relate to ketamine's antidepressant properties. In this prospective two-site study we measured resting state fMRI in 24 depressed patients prior to, and 24 h after a single sub-anesthetic dose of ketamine. We analyzed functional connectivity (FC) at baseline and after ketamine and focused our analysis on baseline FC and FC changes directly linked to symptom reduction in order to identify neuronal targets that predict individual clinical responses to ketamine. Our results show that FC increases after ketamine between right lateral prefrontal cortex (PFC) and subgenual anterior cingulate cortex (sgACC) are positively linked to treatment response. Furthermore, low baseline FC between these regions predicts treatment outcome. We conclude that PFC-sgACC connectivity may represent a promising biomarker with both predictive and explanatory power.

Trial registration: NCT02099630 NCT03609190.

Keywords: Functional connectivity; Ketamine; Major depression; fMRI.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / pharmacology
  • Biomarkers
  • Depression / drug therapy
  • Depression / physiopathology*
  • Female
  • Functional Neuroimaging
  • Gyrus Cinguli / physiology*
  • Humans
  • Ketamine / pharmacology*
  • Ketamine / therapeutic use
  • Magnetic Resonance Imaging
  • Male
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Predictive Value of Tests
  • Prefrontal Cortex / physiology*
  • Young Adult


  • Antidepressive Agents
  • Biomarkers
  • Ketamine

Associated data