Search for plasma biomarkers in drug-free patients with bipolar disorder and schizophrenia using metabolome analysis
Search for plasma biomarkers in drug-free patients with bipolar disorder and schizophrenia using metabolome analysis
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DOI：
10.1111/pcn.12461
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发表时间：
2017-02-01
影响因子：
11.9
通讯作者：
Kato, Tadafumi
中科院分区：
文献类型：
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作者：
Kageyama, Yuki;Kasahara, Takaoki;Kato, Tadafumi
目的：诊断双相情感障碍(BD)和精神分裂症(SZ)的生物标记物的需求十分迫切；然而，药物的混杂作用阻碍了生物标记物的发现。在这项研究中，我们通过代谢组学分析在无药物的BD和SZ患者中寻找新的血浆生物标志物。方法：我们用毛细管电泳联用飞行时间质谱仪综合分析了SZ患者(n=17)、BD患者(n=6)和重度抑郁症患者(n=9)以及匹配的健康对照组(n=19)的血浆代谢物。结果：SZ患者的肌酸水平低于对照组(P=0.016)，而2-羟丁酸水平高于对照组(P分别为0.043和0.043)，而在以前报道的数据集中，这些结果并未发生改变。与对照组相比，BD组名义上瓜氨酸显著降低(未纠正的P=0.043)；然而，这一发现没有在BD用药患者的独立样本中重复。多巴胺的代谢产物N-甲基去甲龙脑醇被认为是BD的候选生物标志物，但另一种分析方法没有检测到它。甜菜碱是先前报道的精神分裂症的候选生物标志物，在当前的数据集中没有变化。结论：我们的初步发现表明，在寻找血浆生物标志物时，应仔细控制混杂因素的影响，如病程和药物治疗。需要进一步的研究来为这些疾病建立强有力的生物标记物。
Aim: There is an urgent need for diagnostic biomarkers of bipolar disorder (BD) and schizophrenia (SZ); however, confounding effects of medication hamper biomarker discovery. In this study, we conducted metabolome analyses to identify novel plasma biomarkers in drug-free patients with BD and SZ.Methods: We comprehensively analyzed plasma metabolites using capillary electrophoresis time-of-flight mass spectrometry in patients with SZ (n = 17), BD (n = 6), and major depressive disorder (n = 9) who had not received psychotropics for at least 2 weeks, and in matched healthy controls (n = 19). The results were compared with previous reports, or verified in an independent sample set using an alternative analytical approach.Results: Lower creatine level and higher 2-hydroxybutyric acid level were observed in SZ than in controls (uncorrected P = 0.016 and 0.043, respectively), whereas they were unaltered in a previously reported dataset. Citrulline was nominally significantly decreased in BD compared to controls (uncorrected P = 0.043); however, this finding was not replicated in an independent sample set of medicated patients with BD. N-methyl-norsalsolinol, a metabolite of dopamine, was suggested as a candidate biomarker of BD; however, it was not detected by the other analytical method. Levels of betaine, a previously reported candidate biomarker of schizophrenia, were unchanged in the current dataset.Conclusion: Our preliminary findings suggest that the effect of confounding factors, such as duration of illness and medication, should be carefully controlled when searching for plasma biomarkers. Further studies are required to establish robust biomarkers for these disorders.