“…Potential patients will be enrolled from the Tianjin Mental Health Center affiliated with Tianjin Medical University in Tianjin, a coastal metropolis in northern China with approximately 13,000,000 residents. Eligible patients will (a) be aged 18–65 years to minimize potential older age‐related confounding effects, such as AD and cognitive impairment; (b) meet the Diagnostic and Statistical Manual of Mental Disorders fifth edition criteria for recurrent MDD without psychotic features, which will be confirmed using the Mini International Neuropsychiatric Interview (Sheehan et al, ; Singh et al, ); (c) have inadequate responses to at least two antidepressant medications, with at least one antidepressant failure to treat current depressive episodes, as evaluated by medical histories, the Massachusetts General Hospital Antidepressant Response Questionnaire, and Montgomery‐Asberg Depression Rating Scale (MADRS) score ≥21 at baseline (Chandler, Iosifescu, Pollack, Targum, & Fava, ; Ng et al, ; Singh et al, ); (d) be willing to participate and fully cooperate in this study; and (e) provide written informed consent prior to study participation. Patients with the following conditions will be considered to be ineligible and will be excluded from the study: (a) severe systemic disease; (b) epilepsy, claustrophobia, primary obsessive–compulsive disorder, anorexia nervosa, bulimia nervosa, or posttraumatic stress disorder; (c) medical history or current diagnosis of a psychotic disorder; (d) medical history or current diagnosis of mental retardation, bipolar disorder, mood disorder with postpartum onset, borderline personality disorder, or somatoform disorder; (e) hypertension or vascular disease, including aneurysm, vascular malformation, thrombosis, and neoplasm; (f) unfitness for MRI, including the presence of a magnetic implant; (g) unfitness for PET, including allergy to PET tracers; (h) substance abuse; (i) use of medicine for a sleep disorder; (j) medical history of nonresponsiveness of depressive symptoms to ketamine; (k) clinically significant suicidal or homicidal ideation or imminent risk of harm; and (l) current pregnancy or breastfeeding status.…”