Regulation of neural responses to emotion perception by ketamine in individuals with treatment-resistant major depressive disorder
James W. Murrough, Katherine A. Collins, Jessica Fields, Kaitlin E. DeWilde, Mary L. Phillips, Sanjay J. Mathew, Edmund Wong, Cheuk Y. Tang, Dennis S. Charney, Dan V. Iosifescu
Translational Psychiatry February 17, 2015 DOI: 10.1038/tp.2015.10 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort with within-subjects pre-post intervention and healthy control group Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Patients with treatment-resistant major depressive disorder (TRD) free of concomitant antidepressant medication |
| Intervention | Ketamine |
| Dose | 0.5 mg kg(-1) |
| Duration | 24 hours |
| Topics | Depression Ketamine Esketamine |
| Keywords | Antidepressant Emotion perception Audiology Anesthesia Amygdala Hippocampus Cognition |
| Citations | 111 |
| Key findings | Ketamine enhances neural responses to positive emotion within the right caudate in depressed individuals, reversing baseline deficits, and connectivity of this region may be important for antidepressant effects. |
Abstract
The glutamate N-methyl-D-aspartate receptor antagonist ketamine has demonstrated antidepressant effects in individuals with treatment-resistant major depressive disorder (TRD) within 24 h of a single dose. The current study utilized functional magnetic resonance imaging (fMRI) and two separate emotion perception tasks to examine the neural effects of ketamine in patients with TRD. One task used happy and neutral facial expressions; the other used sad and neutral facial expressions. Twenty patients with TRD free of concomitant antidepressant medication underwent fMRI at baseline and 24 h following administration of a single intravenous dose of ketamine (0.5 mg kg(-1)). Adequate data were available for 18 patients for each task. Twenty age- and sex-matched healthy volunteers were scanned at one time point for baseline comparison. Whole-brain, voxel-wise analyses were conducted controlling for a family-wise error rate (FWE) of P<0.05. Compared with healthy volunteers, TRD patients showed reduced neural responses to positive faces within the right caudate. Following ketamine, neural responses to positive faces were selectively increased within a similar region of right caudate. Connectivity analyses showed that greater connectivity of the right caudate during positive emotion perception was associated with improvement in depression severity following ketamine. No main effect of group was observed for the sad faces task. Our results indicate that ketamine specifically enhances neural responses to positive emotion within the right caudate in depressed individuals in a pattern that appears to reverse baseline deficits and that connectivity of this region may be important for the antidepressant effects of ketamine.
Comparable studies
Other non-randomized and open-label trials on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder Subjects with DSM-IV-diagnosed treatment-resistant major depressive disorder | 2010 | Open-label trial | n = 33 |
| Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression Adults (≥ 18 years) with treatment-resistant depression | 2020 | Phase 3, open-label, multicenter, long-term study | n = 802 |
| Intravenous arketamine for treatment-resistant depression: open-label pilot study Humans with treatment-resistant depression | 2020 | Open-label pilot trial | n = 7 |
| A Phase 2 Open Label Study of Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) in Adults with MDD at Imminent Risk of Suicide. Hospitalized patients with Major Depressive Disorder and acute suicidal ideation and... | 2024 | Open label study | n = 17 |
| Ketamine Safety and Tolerability in Clinical Trials for Treatment-Resistant Depression Participants with DSM-IV-defined major depressive disorder and treatment-resistant... | 2014 | Pooled analysis of three clinical trials | n = 97 |
Citations in the library
Cited by 45
- A Phase 2 Open Label Study of Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) in Adults with MDD at Imminent Risk of Suicide. Psychopharmacology Bulletin March 4, 2024
- KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS Depression and Anxiety April 6, 2016
- Ketamine modulates fronto-striatal circuitry in depressed and healthy individuals Molecular Psychiatry September 14, 2020
- The anterior cingulate cortex as a key locus of ketamine’s antidepressant action Neuroscience & Biobehavioral Reviews May 10, 2021
- Ketamine administration reduces amygdalo‐hippocampal reactivity to emotional stimulation Human Brain Mapping February 25, 2016
and 40 more in the library
Cites 8
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial The International Journal of Neuropsychopharmacology March 17, 2009
and 3 more in the library