Predicting Antidepressant Effects of Ketamine: the Role of the Pregenual Anterior Cingulate Cortex as a Multimodal Neuroimaging Biomarker

Anne Weigand, Matti Gärtner, Milan Scheidegger, Patrik O. Wyss, Anke Henning, Erich Seifritz, Anna Stippl, Ana Herrera-Melendez, Malek Bajbouj, Sabine Aust, Simone Grimm

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


BACKGROUND: Growing evidence underscores the utility of ketamine as an effective and rapid-acting treatment option for major depressive disorder (MDD). However, clinical outcomes vary between patients. Predicting successful response may enable personalized treatment decisions and increase clinical efficacy. METHODS: We here explored the potential of pregenual anterior cingulate cortex (pgACC) activity to predict antidepressant effects of ketamine in relation to ketamine-induced changes in glutamatergic metabolism. Prior to a single i.v. infusion of ketamine, 24 patients with MDD underwent functional magnetic resonance imaging during an emotional picture-viewing task and magnetic resonance spectroscopy. Changes in depressive symptoms were evaluated using the Beck Depression Inventory measured 24 hours pre- and post-intervention. A subsample of 17 patients underwent a follow-up magnetic resonance spectroscopy scan. RESULTS: Antidepressant efficacy of ketamine was predicted by pgACC activity during emotional stimulation. In addition, pgACC activity was associated with glutamate increase 24 hours after the ketamine infusion, which was in turn related to better clinical outcome. CONCLUSIONS: Our results add to the growing literature implicating a key role of the pgACC in mediating antidepressant effects and highlighting its potential as a multimodal neuroimaging biomarker of early treatment response to ketamine.

Original languageEnglish (US)
Pages (from-to)1003-1013
Number of pages11
JournalThe international journal of neuropsychopharmacology
Issue number12
StatePublished - Dec 12 2022


  • antidepressant effects
  • ketamine
  • multimodal neuroimaging biomarker
  • pgACC
  • pregenual anterior cingulate cortex

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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