Acylcarnitine metabolomic profiles inform clinically-defined major depressive phenotypes
Acylcarnitine metabolomic profiles inform clinically-defined major depressive phenotypes
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DOI：
10.1016/j.jad.2019.11.122
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发表时间：
2020-03-01
影响因子：
6.6
通讯作者：
Kaddurah-Daouk, Rima
中科院分区：
文献类型：
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作者：
Ahmed, Ahmed T.;MahmoudianDehkordi, Siamak;Kaddurah-Daouk, Rima
背景：酰卡尼汀在线粒体能量学和β-氧化中具有重要作用，并被认为在大脑的代谢功能中发挥重要作用。这项回顾研究探讨了血浆酰卡尼汀水平是否有助于区分严重抑郁障碍(MDD)的三个表型亚型：核心抑郁(CD+)、焦虑性抑郁(ANX+)和神经植物性忧郁症(NVSM+)。方法：来自梅奥临床药物基因组学研究网络的240例抑郁症患者接受西酞普兰或艾司匹兰治疗8周。使用AbsolteIDQ(R)P180-Kit和LC-MS分析在基线和西酞普兰或艾司匹兰治疗8周后收集的血浆样本中短、中和长链酰肉碱的水平。结果：与ANX+相比，Cd+和NVSM+在基线和治疗8周时的短链和长链酰基肉碱浓度均显著降低。在NVSM+中，NVSM+的中链和长链酰肉碱的浓度也显著低于ANX+。从基线到第8周，Cd+和ANX+的短链酰肉碱水平显著升高，而Cd+和NVSM+的中链和长链酰肉碱水平显著下降。结论：在SSRIs治疗的抑郁症患者中，β-氧化和线粒体能量学的水平和变化可能为MDD的临床异质性提供生化基础，特别是结合临床特征。
Background: Acylcarnitines have important functions in mitochondrial energetics and beta-oxidation, and have been implicated to play a significant role in metabolic functions of the brain. This retrospective study examined whether plasma acylcarnitine profiles can help biochemically distinguish the three phenotypic subtypes of major depressive disorder (MDD): core depression (CD+), anxious depression (ANX+), and neurovegetative symptoms of melancholia (NVSM+).Methods: Depressed outpatients (n = 240) from the Mayo Clinic Pharmacogenomics Research Network were treated with citalopram or escitalopram for eight weeks. Plasma samples collected at baseline and after eight weeks of treatment with citalopram or escitalopram were profiled for short-, medium- and long-chain acylcarnitine levels using AbsoluteIDQ (R) p180-Kit and LC-MS. Linear mixed effects models were used to examine whether acylcarnitine levels discriminated the clinical phenotypes at baseline or eight weeks post-treatment, and whether temporal changes in acylcarnitine profiles differed between groups.Results: Compared to ANX+, CD+ and NVSM+ had significantly lower concentrations of short- and long-chain acylcarnitines at both baseline and week 8. In NVSM+, the medium- and long-chain acylcarnitines were also significantly lower in NVSM+ compared to ANX+. Short-chain acylcarnitine levels increased significantly from baseline to week 8 in CD+ and ANX+, whereas medium- and long-chain acylcarnitines significantly decreased in CD+ and NVSM+.Conclusions: In depressed patients treated with SSRIs, beta-oxidation and mitochondrial energetics as evaluated by levels and changes in acylcarnitines may provide the biochemical basis of the clinical heterogeneity of MDD, especially when combined with clinical characteristics.