The therapeutic antidepressant effect of S-ketamine has been linked to changes in glutamatergic neurotransmission. Here, we investigated the value of dynamic functional MRS compared to static MRS in detecting dose-dependent effects of subanesthetic S-ketamine on glutamate in the anterior cingulate cortex. Although significant dose-dependent subjective dissociative effects of S-ketamine were observed, we did not find significantly different glutamate changes between placebo, low-dose S-ketamine and high-dose S-ketamine, using either a “static” or “dynamic” analysis approach. Nevertheless, exploratory analyses suggest that glutamate might be modulated at specific time-points after S-ketamine administration, illustrating the potential additional information obtained from a dynamic approach.
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