Integrating Ketamine Effects on Neuronal Molecular Signatures and the Brain Functional and Structural Connectome

Inclusion Criteria:

* 1\. Able to give voluntary informed consent; 2. Satisfy criteria for Diagnostic and Statistical Manual 5th edition (DSM-V) for Major Depression Disorder (MDD) 3. Currently in a depressive episode (MDE); 4. Montgomery and Asberg Depression Rating Scale (MADRS) score \>21 but \<32(moderate to severe depression)11; 3. Psychotropic medication-free \> 2weeks and if on fluoxetine then for \>5 weeks at time of inclusion in the study(no taper or medication washout will be done for the purpose of the study). 6. Satisfy criteria to undergo an MRI scan based on MRI screening questionnaire; 7) able to be managed as outpatients during the study as ascertained by Clinical Global Severity Scale \< 5 (i.e., moderately ill) and no suicidal/homicidal intent or behavior or gross disability; and 8) no contraindication to KET treatment such as KET allergy or uncontrolled hypertension.

Exclusion Criteria:

* 1\. Meeting DSM-5 criteria for (hypo)mania, bipolar disorder, schizophrenia, schizophreniform disorder, schizoaffective disorder, intellectual disability, or pervasive developmental disorder; 2. History of receiving electroconvulsive therapy in the past 1 year (due to possible effects on brain morphology); 3. Meeting DSM-5 criteria for moderate or severe substance/alcohol use within the past 6 months excluding caffeine or nicotine. The criteria will be evaluated by interview and urinary toxicology screening. The typical weekly use of caffeine, nicotine and alcohol will be recorded; 4. No serious medical or neurological illness, including previously known HIV positive status (due to possible CNS involvement) as assessed by history, physical examination and laboratory examination including EKG, CBC and blood chemistry; 5. Current pregnancy or breast feeding; 6. Metallic implants or contraindication to MRI.