Increased anterior cingulate cortical activity in response to fearful faces: a neurophysiological biomarker that predicts rapid antidepressant response to ketamine.
Giacomo Salvadore, Brian R Cornwell, Veronica Colon-Rosario, Richard Coppola, Christian Grillon, Carlos A. Zarate, Husseini Manji
Biological Psychiatry February 15, 2009 DOI: 10.1016/j.biopsych.2008.08.014 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational case-control study with subsequent open-label ketamine infusion Peer reviewed |
|---|---|
| Sample size | 22 |
| Population | Drug-free patients with major depressive disorder (n=11) and healthy control subjects (n=11) |
| Intervention | Ketamine |
| Duration | Depressive symptoms assessed 4 hours after a single ketamine infusion |
| Topics | Esketamine Ketamine |
| Key findings | Patients with major depressive disorder showed robust increases in pretreatment rostral anterior cingulate cortex activity across repeated fearful-face presentations, whereas healthy controls showed decreased activity. This increase was positively correlated with rapid antidepressant response to a single ketamine infusion four hours later. Exploratory analyses found pretreatment amygdala activity negatively correlated with change in depressive symptoms. The authors suggest pretreatment rostral ACC activation may be a useful biomarker for identifying ketamine responders. |
Abstract
Most patients with major depressive disorder (MDD) experience a period of lengthy trial and error when trying to find optimal antidepressant treatment; identifying biomarkers that could predict response to antidepressant treatment would be of enormous benefit. We tested the hypothesis that pretreatment anterior cingulate cortex (ACC) activity could be a putative biomarker of rapid antidepressant response to ketamine, in line with previous findings that investigated the effects of conventional antidepressants. We also investigated patterns of ACC activity to rapid presentation of fearful faces compared with the normal habituation observed in healthy subjects. We elicited ACC activity in drug-free patients with MDD (n = 11) and healthy control subjects (n = 11) by rapidly presenting fearful faces, a paradigm known to activate rostral regions of the ACC. Spatial-filtering analyses were performed on magnetoencephalographic (MEG) recordings, which offer the temporal precision necessary to estimate ACC activity elicited by the rapid presentation of stimuli. Magnetoencephalographic recordings were obtained only once for both patients and control subjects. Patients were subsequently administered a single ketamine infusion followed by assessment of depressive symptoms 4 hours later. Although healthy subjects had decreased neuromagnetic activity in the rostral ACC across repeated exposures, patients with MDD showed robust increases in pretreatment ACC activity. Notably, this increase was positively correlated with subsequent rapid antidepressant response to ketamine. Exploratory analyses showed that pretreatment amygdala activity was negatively correlated with change in depressive symptoms. Pretreatment rostral ACC activation may be a useful biomarker that identifies a subgroup of patients who will respond favorably to ketamine's antidepressant effects.
Comparable studies
Other non-randomized and open-label trials on ketamine, most cited first.
Citations in the library
Cited by 76
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder The Journal of Clinical Psychiatry July 13, 2010
- Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics Annual Review of Medicine October 23, 2014
- Ketamine Decreases Resting State Functional Network Connectivity in Healthy Subjects: Implications for Antidepressant Drug Action PLoS One September 24, 2012
- The use of ketamine as an antidepressant: a systematic review and meta‐analysis Human Psychopharmacology: Clinical and Experimental April 7, 2015
and 71 more in the library
Cites 4
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Glutamate and the Neural Basis of the Subjective Effects of Ketamine Archives of General Psychiatry February 1, 2008
- Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biological Psychiatry February 15, 2008
- The role of glutamate in mood disorders: results from the ketamine in major depression study and the presumed cellular mechanism underlying its antidepressant effects. Current Psychiatry Reports December 2007