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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 Lucía Herrera-Meléndez, Malek Bajbouj, Sabine Aust, Simone Grimm

The International Journal of Neuropsychopharmacology August 10, 2022 DOI: 10.1093/ijnp/pyac049 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Peer reviewed
Sample size 24
Population Patients with major depressive disorder
Intervention Ketamine
Dose single i.v. infusion of ketamine
Duration 24 hours pre- and post-intervention; a subsample of 17 patients had a follow-up scan at 24 hours
Topics Depression Ketamine Esketamine
Keywords Anterior cingulate cortex Antidepressant Neuroimaging Beck depression inventory Magnetic resonance imaging Biomarker Hippocampus Amygdala Cognition Radiology
Citations 22
Key findings Pregenual anterior cingulate cortex activity during emotional stimulation predicts antidepressant response to ketamine, and this activity is associated with a post-infusion glutamate increase that relates to better clinical outcome.

Abstract

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.

Comparable studies

Other observational and cohort studies on ketamine for depression, most cited first.

Study Year Design Participants
Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder 2012 Observational cohort n = 30
Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... 2017 Observational cohort n = 59
Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... 2014 Post hoc analysis of pooled data from four studies n = 108
An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder 2011 Observational cohort n = 14
Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... 2019 Observational cohort n = 25

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