The glutamatergic modulator ketamine has striking and rapid antidepressant effects in major depressive disorder (MDD), but its mechanism of action remains unknown. Proton magnetic resonance spectroscopy (1H-MRS) is the only non-invasive method able to directly measure glutamate levels in vivo; in particular, glutamate and glutamine metabolite concentrations are separable by 1H-MRS at 7T. This double-blind, placebo-controlled, crossover study that included 1H-MRS scans at baseline and at 24 h post ketamine and post-placebo infusions sought to determine glutamate levels in the pregenual anterior cingulate (pgACC) of 20 medication-free MDD subjects and 17 healthy volunteers (HVs) 24 h post ketamine administration, and to evaluate any other measured metabolite changes, correlates, or predictors of antidepressant response. Metabolite levels were compared at three scan times (baseline, post-ketamine, and post-placebo) in HVs and MDD subjects at 7T using a 1H-MRS sequence specifically optimized for glutamate. No significant between-group differences in 1H-MRS-measured metabolites were observed at baseline. Antidepressant response was not predicted by baseline glutamate levels. Our results suggest that any infusion-induced increases in glutamate at the 24-h post ketamine time point were below the sensitivity of the current technique; that these increases may occur in different brain regions than the pgACC; or that subgroups of MDD subjects may exist that have a differential glutamate response to ketamine.

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7T 1H-MRS在重度抑郁症中的应用：氯胺酮治疗研究。

谷氨酸能调节剂氯胺酮在重度抑郁症（MDD）中具有惊人的快速抗抑郁作用，但其作用机理仍然未知。质子磁共振波谱（1H-MRS）是唯一能够直接测量体内谷氨酸水平的非侵入性方法。特别是，谷氨酸和谷氨酰胺代谢物的浓度在7T时可通过1H-MRS进行分离。这项双盲，安慰剂对照的交叉研究包括在基线和氯胺酮注射后24小时进行1H-MRS扫描，安慰剂注射后试图确定20名无药物MDD受试者的前扣带回（pgACC）中的谷氨酸水平和17名健康志愿者（HV）在氯胺酮给药后24小时，并评估其他任何测量的代谢物变化，相关性或抗抑郁反应的预测因子。使用专门针对谷氨酸优化的1H-MRS序列，在7T的HV和MDD受试者中，在三个扫描时间（基线，氯胺酮后和安慰剂后）比较了代谢物水平。在基线时，未观察到1H-MRS测定的代谢物的显着组间差异。基线谷氨酸水平不能预测抗抑郁药的反应。我们的结果表明，氯胺酮注射后24小时内任何由输液引起的谷氨酸增加均低于当前技术的敏感性；这些增加可能发生在与pgACC不同的大脑区域中；或可能存在对氯胺酮的谷氨酸反应不同的MDD受试者亚组。在基线时，未观察到1H-MRS测定的代谢物的显着组间差异。基线谷氨酸水平不能预测抗抑郁药的反应。我们的结果表明，氯胺酮注射后24小时内任何由输液引起的谷氨酸增加均低于当前技术的敏感性；这些增加可能发生在与pgACC不同的大脑区域中；或可能存在对氯胺酮的谷氨酸反应不同的MDD受试者亚组。在基线时，未观察到1H-MRS测定的代谢物的显着组间差异。基线谷氨酸水平不能预测抗抑郁药的反应。我们的结果表明，氯胺酮注射后24小时内任何由输液引起的谷氨酸增加均低于当前技术的敏感性；这些增加可能发生在与pgACC不同的大脑区域中；或可能存在对氯胺酮的谷氨酸反应不同的MDD受试者亚组。这些增加可能发生在与pgACC不同的大脑区域中；或可能存在对氯胺酮的谷氨酸反应不同的MDD受试者亚组。这些增加可能发生在与pgACC不同的大脑区域中；或可能存在对氯胺酮的谷氨酸反应不同的MDD受试者亚组。