Plasma metabolomic profiling of a ketamine and placebo crossover trial of major depressive disorder and healthy control subjects.

(R,S)-Ketamine produces rapid, robust, and sustained antidepressant effects in major depressive disorder. Specifically, its pharmacological efficacy in treatment refractory depression is considered a major breakthrough in the field. However, the mechanism of action of ketamine’s rapid effect remains...

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Publicado en:Psychopharmacology Vol. 235; no. 10; pp. 3017 - 3031
Autores principales: Moaddel, Ruin, Shardell, Michelle, Khadeer, Mohammed, Lovett, Jacqueline, Kadriu, Bashkim, Ravichandran, Sarangan, Morris, Patrick J., Yuan, Peixiong, Thomas, Craig J., Gould, Todd D., Ferrucci, Luigi, Zarate, Carlos A.
Formato: Journal Article
Publicado: Springer Nature Oct2018
Acceso en línea:Ver este registro en EBSCOhost
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00213-018-4992-7
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        atl: Plasma metabolomic profiling of a ketamine and placebo crossover trial of major depressive disorder and healthy control subjects.
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        au:
          Moaddel, Ruin
          Shardell, Michelle
          Khadeer, Mohammed
          Lovett, Jacqueline
          Kadriu, Bashkim
          Ravichandran, Sarangan
          Morris, Patrick J.
          Yuan, Peixiong
          Thomas, Craig J.
          Gould, Todd D.
          Ferrucci, Luigi
          Zarate, Carlos A.
        affil: Biomedical Research Center, Intramural Research Program, National Institute on Aging, National Institutes, Bethesda, MD, USA
      sug:
      ab: (R,S)-Ketamine produces rapid, robust, and sustained antidepressant effects in major depressive disorder. Specifically, its pharmacological efficacy in treatment refractory depression is considered a major breakthrough in the field. However, the mechanism of action of ketamine’s rapid effect remains to be determined. In order to identify pathways that are responsible for ketamine’s effect, a targeted metabolomic approach was carried out using a double-blind, placebo-controlled crossover design, with infusion order randomized with medication-free patients with treatment-resistant major depressive disorder (29 subjects) and healthy controls (25 subjects). The metabolomic profile of these subjects was characterized at multiple time points, and a comprehensive analysis was investigated between the following: MDD and healthy controls, treatment and placebo in both groups and the corresponding response to ketamine treatment. Ketamine treatment resulted in a general increase in circulating sphingomyelins, levels which were not correlated with response. Ketamine response resulted in more pronounced effects in the kynurenine pathway and the arginine pathway at 4 h post-infusion, where a larger decrease in circulating kynurenine levels and a larger increase in the bioavailability of arginine were observed in responders to ketamine treatment, suggesting possible mechanisms for response to ketamine treatment.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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