The Role of HNKs in the Antidepressant Effect of Ketamine

Inclusion Criteria: * Current major depressive episode (MDE) as part of major depressive disorder (MDD). May be psychiatric medication-free or, if on psychiatric medications, not responding adequately. * Off all psychotropic and other types of drugs likely to interact with glutamate for at least 14 days before starting the study OR likely able to tolerate a medication washout. * Female subjects of child-bearing potential must be using an acceptable method of birth control throughout the study. Exclusion Criteria: * Lifetime history of schizophrenia, schizoaffective illness, bipolar disorder, or psychosis. * First-degree relative with schizophrenia, schizoaffective disorder, or bipolar disorder if the subject is less than 33 years old. * Significant uncontrolled physical illness. * Electroconvulsive therapy (ECT) within the last 3 months for current MDE. * Pregnancy or plans to conceive during the course of study participation. * Heart pacemaker, body implant or other metal in body. * Neurological disease or prior head trauma with evidence of cognitive impairment. * Claustrophobia sufficient to preclude MRI. * Prior ineffective trial of, or adverse effect to, ketamine. * IV drug use or history of ketamine use as a recreational drug ≥ 2 times or an adverse reaction to ketamine; any other drug or alcohol dependence within past 6 months.