Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-Ku, Fukuoka, 812-8582, Japan.
Sci Rep. 2020 Oct 8;10(1):16822. doi: 10.1038/s41598-020-73918-z.
Since optimal treatment at an early stage leads to remission of symptoms and recovery of function, putative biomarkers leading to early diagnosis and prediction of therapeutic responses are desired. The current study aimed to use a metabolomic approach to extract metabolites involved in both the diagnosis of major depressive disorder (MDD) and the prediction of therapeutic response for escitalopram. We compared plasma metabolites of MDD patients (n = 88) with those in healthy participants (n = 88) and found significant differences in the concentrations of 20 metabolites. We measured the Hamilton Rating Scale for Depression (HRSD) on 62 patients who completed approximately six-week treatment with escitalopram before and after treatment and found that kynurenic acid and kynurenine were significantly and negatively associated with HRSD reduction. Only one metabolite, kynurenic acid, was detected among 73 metabolites for overlapped biomarkers. Kynurenic acid was lower in MDD, and lower levels showed a better therapeutic response to escitalopram. Kynurenic acid is a metabolite in the kynurenine pathway that has been widely accepted as being a major mechanism in MDD. Overlapping biomarkers that facilitate diagnosis and prediction of the treatment response may help to improve disease classification and reduce the exposure of patients to less effective treatments in MDD.
由于早期的最佳治疗可以缓解症状和恢复功能，因此需要能够早期诊断和预测治疗反应的潜在生物标志物。本研究旨在采用代谢组学方法提取与重度抑郁症（MDD）的诊断和依西酞普兰治疗反应预测相关的代谢物。我们比较了 MDD 患者（n=88）和健康参与者（n=88）的血浆代谢物，发现 20 种代谢物的浓度存在显著差异。我们对 62 名完成大约六周依西酞普兰治疗的患者进行了汉密尔顿抑郁量表（HRSD）测量，结果发现治疗前后，犬尿酸和犬尿氨酸与 HRSD 降低呈显著负相关。在重叠的生物标志物中，只有一种代谢物，犬尿酸被检测到。犬尿酸在 MDD 中较低，较低的水平表明对依西酞普兰的治疗反应更好。犬尿酸是犬尿氨酸途径中的一种代谢物，已被广泛认为是 MDD 的主要机制之一。有助于诊断和预测治疗反应的重叠生物标志物可能有助于改善疾病分类，并减少 MDD 患者对疗效较低的治疗方法的暴露。
