Plasma metabolomic profiling of a ketamine and placebo crossover trial of major depressive disorder and healthy control subjects.
Plasma metabolomic profiling of a ketamine and placebo crossover trial of major depressive disorder and healthy control subjects.
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重度抑郁症和健康对照受试者的氯胺酮和安慰剂跨界试验的血浆代谢组分析。
DOI：
10.1007/s00213-018-4992-7
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发表时间：
2018-10
影响因子：
3.4
通讯作者：
Zarate CA
中科院分区：
文献类型：
--
作者：
Moaddel R;Shardell M;Khadeer M;Lovett J;Kadriu B;Ravichandran S;Morris PJ;Yuan P;Thomas CJ;Gould TD;Ferrucci L;Zarate CA
(R,S)-氯胺酮对重度抑郁症产生快速、强大和持续的抗抑郁作用。具体来说，其治疗难治性抑郁症的药理功效被认为是该领域的重大突破。然而，氯胺酮快速起效的作用机制仍有待确定。为了确定氯胺酮作用的途径，采用双盲、安慰剂对照交叉设计进行了靶向代谢组学方法，将输注顺序随机分配给未接受药物治疗的难治性重度抑郁症患者（29 名受试者）和健康对照者（25 名受试者）。这些受试者的代谢组学特征在多个时间点进行了表征，并对以下各项进行了综合分析：MDD 和健康对照、两组的治疗和安慰剂以及对氯胺酮治疗的相应反应。氯胺酮治疗导致循环鞘磷脂普遍增加，其水平与反应无关。输注后 4 小时，氯胺酮反应对犬尿氨酸途径和精氨酸途径产生更明显的影响，在氯胺酮治疗的反应者中观察到循环犬尿氨酸水平大幅下降和精氨酸生物利用度大幅增加，这表明对氯胺酮治疗反应的可能机制。
(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.
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影响因子：
6.6
作者：
Ali-Sisto, Toni;Tolmunen, Tommi;Lehto, Soili M.
通讯作者：
Lehto, Soili M.
DOI：
10.4088/jcp.09m05327blu
发表时间：
2010-12
期刊：
The Journal of clinical psychiatry
影响因子：
--
作者：
DiazGranados N;Ibrahim LA;Brutsche NE;Ameli R;Henter ID;Luckenbaugh DA;Machado-Vieira R;Zarate CA Jr
通讯作者：
Zarate CA Jr
影响因子：
10.6
作者：
Berman, RM;Cappiello, A;Krystal, JH
通讯作者：
Krystal, JH
影响因子：
3.7
作者：
Baranyi A;Amouzadeh-Ghadikolai O;Rothenhäusler HB;Theokas S;Robier C;Baranyi M;Koppitz M;Reicht G;Hlade P;Meinitzer A
通讯作者：
Meinitzer A
影响因子：
4
作者：
Dobos, Nikoletta;de Vries, Erik F. J.;Eisel, Ulrich L. M.
通讯作者：
Eisel, Ulrich L. M.