Table_2_Discovery and validation of acetyl-L-carnitine in serum for diagnosis of major depressive disorder and remission status through metabolomic approach.docx

Major depressive disorder (MDD) is one of the most common psychiatric disorders that accompany psychophysiological and mood changes. However, the pathophysiology-based disease mechanism of MDD is not yet fully understood, and diagnosis is also conducted through interviews with clinicians and patients. Diagnosis and treatment of MDD are limited due to the absence of biomarkers underlying the pathophysiological mechanisms of MDD. Although various attempts have been made to discover metabolite biomarkers for the diagnosis and treatment response of MDD, problems with sample size and consistency of results have limited clinical application. In addition, it was reported that future biomarker studies must consider exposure to antidepressants, which is the main cause of heterogeneity in depression subgroups. Therefore, the purpose of this study is to discover and validate biomarkers for the diagnosis of depression in consideration of exposure to drug treatment including antidepressants that contribute to the heterogeneity of the MDD subgroup. In the biomarker discovery and validation set, the disease group consisted of a mixture of patients exposed and unexposed to drug treatment including antidepressants for the treatment of MDD. The serum metabolites that differed between the MDD patients and the control group were profiled using mass spectrometry. The validation set including the remission group was used to verify the effectiveness as a biomarker for the diagnosis of depression and determination of remission status. The presence of different metabolites between the two groups was confirmed through serum metabolite profiling between the MDD patient group and the control group. Finally, Acetylcarnitine was selected as a biomarker. In validation, acetylcarnitine was significantly decreased in MDD and was distinguished from remission status. This study confirmed that the discovered acetylcarnitine has potential as a biomarker for diagnosing depression and determining remission status, regardless of exposure to drug treatment including antidepressants.

重度抑郁症（MDD）是伴随心理生理和情绪变化的最为常见的心理障碍之一。然而，MDD的病理生理学发病机制尚未完全明了，其诊断主要依赖于临床医生与患者的访谈。由于缺乏MDD病理生理机制下的生物标志物，MDD的诊断和治疗受到限制。尽管已尝试发现MDD的诊断和治疗反应的代谢物生物标志物，但样本量问题和结果的一致性问题限制了其临床应用。此外，据报道，未来的生物标志物研究必须考虑抗抑郁药等药物暴露，这是导致抑郁亚组异质性的主要原因。因此，本研究旨在发现并验证考虑药物治疗（包括抗抑郁药）暴露的抑郁症生物标志物。在生物标志物发现和验证集中，疾病组由接受和不接受包括抗抑郁药在内的MDD治疗的患者的混合体组成。利用质谱技术对MDD患者组和对照组之间的血清代谢物差异进行了分析。包括缓解组在内的验证集被用于验证其作为抑郁症诊断生物标志物及确定缓解状态的有效性。通过MDD患者组和对照组之间的血清代谢物分析，证实了两组之间存在不同的代谢物。最终，乙酰肉碱被选为生物标志物。在验证中，乙酰肉碱在MDD患者中显著降低，并且与缓解状态区分开来。本研究证实，所发现的乙酰肉碱作为诊断抑郁症和确定缓解状态的生物标志物具有潜力，无论是否暴露于包括抗抑郁药在内的药物治疗。