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 |
Citations in the library
Cited by 14
- Esketamine in depression: putative biomarkers from clinical research. European Archives of Psychiatry and Clinical Neuroscience July 13, 2024
- Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamine Translational Psychiatry February 16, 2023
- Ketamine and Zinc: Treatment of Anorexia Nervosa Via Dual NMDA Receptor Modulation CNS Drugs January 22, 2023
- Neural correlates of treatment response to ketamine for treatment-resistant depression: A systematic review of MRI-based studies. Psychiatry Research October 1, 2024
- Recommendations for selection and adaptation of rating scales for clinical studies of rapid-acting antidepressants. Frontiers in Psychiatry 2023
and 9 more in the library
Cites 21
- A default mode of brain function Proceedings of the National Academy of Sciences January 16, 2001
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
and 16 more in the library