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7T 1H-MRS in major depressive disorder: a Ketamine Treatment Study.


ABSTRACT: 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.

SUBMITTER: Evans JW 

PROVIDER: S-EPMC6046051 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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7T <sup>1</sup>H-MRS in major depressive disorder: a Ketamine Treatment Study.

Evans Jennifer W JW   Lally Níall N   An Li L   Li Ningzhi N   Nugent Allison C AC   Banerjee Dipavo D   Snider Sam L SL   Shen Jun J   Roiser Jonathan P JP   Zarate Carlos A CA  

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20180405 9


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 <sup>1</sup>H-MRS scans at baseline and  ...[more]

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