Assessment of Relationship of Ketamine Dose With Magnetic Resonance Spectroscopy of Glx and GABA Responses in Adults With Major Depression

作者：Matthew S. Milak, Rain Rashid, Zhengchao Dong, Lawrence S. Kegeles, Michael F. Grunebaum, R. Todd Ogden, Xuejing Lin, Stephanie Mulhern, Raymond F. Suckow, Thomas B. Cooper, John G. Keilp, Xiangling Mao, Dikoma C. Shungu, J. John Mann · 发表于：JAMA Network Open · 年份：2020 · DOI：10.1001/jamanetworkopen.2020.13211 · 被引用次数：60 · 研究领域：Treatment of Major Depression、Tryptophan and brain disorders、Functional Brain Connectivity Studies

Importance: A single subanesthetic dose of ketamine produces an antidepressant response in patients with major depressive disorder (MDD) within hours, but the mechanism of antidepressant effect is uncertain. Objective: To evaluate whether ketamine dose and brain glutamate and glutamine (Glx) and γ-aminobutyric acid (GABA) level responses to ketamine are related to antidepressant benefit and adverse effects. Design, Setting, and Participants: This randomized, parallel-group, triple-masked clinical trial included 38 physically healthy, psychotropic medication-free adult outpatients who were in a major depressive episode of MDD but not actively suicidal. The trial was conducted at Columbia University Medical Center. Data were collected from February 2012 to May 2015. Data analysis was conducted from January to March 2020. Intervention: Participants received 1 dose of placebo or ketamine (0.1, 0.2, 0.3, 0.4, or 0.5 mg/kg) intravenously during 40 minutes of a proton magnetic resonance spectroscopy scan that measured ventro-medial prefrontal cortex Glx and GABA levels in 13-minute data frames. Main Outcomes and Measures: Clinical improvement was measured using a 22-item version of the Hamilton Depression Rating Scale (HDRS-22) 24 hours after ketamine was administered. Ketamine and metabolite blood levels were measured after the scan. Results: A total of 38 individuals participated in the study, with a mean (SD) age of 38.6 (11.2) years, 23 (60.5%) women, and 25 (65.8%) White patien...