title: Regulation of neural responses to emotion perception by ketamine in individuals with treatment-resistant major depressive disorder.
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.
authors.affiliation: 1] Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA [3] Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Murrough
authors.affiliation: Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Collins
authors.affiliation: Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Fields
authors.affiliation: Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: DeWilde
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Phillips
authors.affiliation: 1] Michael E. DeBakey VA Medical Center, Houston, TX, USA [2] Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Mathew
authors.affiliation: 1] Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: E
authors.initials: E
authors.lastname: Wong
authors.affiliation: 1] Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: C Y
authors.initials: CY
authors.lastname: Tang
authors.affiliation: 1] Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA [3] Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Charney
authors.affiliation: 1] Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA [3] Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: D V
authors.initials: DV
authors.lastname: Iosifescu
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D016022:Case-Control Studies; D002421:Caudate Nucleus / Q000187:drug effects* / Q000503:physiopathology; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy / Q000503:physiopathology*; D004644:Emotions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D005149:Facial Expression; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D007649:Ketamine / Q000494:pharmacology* / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D010364:Pattern Recognition, Visual; D012938:Social Perception; D055815:Young Adult
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine