Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
J Affect Disord. 2018 Apr 15;231:74-82. doi: 10.1016/j.jad.2018.01.014. Epub 2018 Jan 31.
Early intervention in depression has been critical to prevent its negative impact including suicide. Recent blood biomarker studies for major depressive disorder (MDD) have suggested that tryptophan-kynurenine and lipid related metabolites are involved in the pathophysiology of MDD. However, there have been limited studies investigating these blood biomarkers in first-episode drug-naïve MDD, which are particularly important for early intervention in depression.
As an exploratory pilot case-control study, we examined the above blood biomarkers, and analyzed how these biomarkers are associated with clinical variables in first-episode drug-naïve MDD patients, based on metabolome/lipidome analysis.
Plasma tryptophan and kynurenine levels were significantly lower in MDD group (N = 15) compared to healthy controls (HC) group (N = 19), and plasma tryptophan was the significant biomarker to identify MDD group (area under the curve = 0.740). Lower serum high density lipoprotein-cholesterol (HDL-C) was the predictive biomarker for severity of depression in MDD group (R = 0.444). Interestingly, depressive symptoms were variously correlated with plasma tryptophan-kynurenine and lipid related metabolites. Moreover, plasma tryptophan-kynurenine metabolites and cholesteryl esters (CEs) were significantly correlated in MDD group, but not in HC group.
This study had small sample size, and we did not use the multiple test correction.
This is the first study to suggest that not only tryptophan-kynurenine metabolites but also HDL-C and CEs are important blood biomarkers for first-episode drug-naïve MDD patients. The present study sheds new light on early intervention in clinical practice in depression, and further clinical studies especially large-scale prospective studies are warranted.
早期干预抑郁症对于防止其负面影响（包括自杀）至关重要。最近的重度抑郁症（MDD）血液生物标志物研究表明，色氨酸-犬尿氨酸和脂质相关代谢物与 MDD 的病理生理学有关。然而，针对初发、未经药物治疗的 MDD 患者的这些血液生物标志物的研究有限，而这些标志物对于抑郁症的早期干预尤为重要。
作为一项探索性的病例对照研究，我们根据代谢组学/脂质组学分析，检查了上述血液生物标志物，并分析了这些标志物与初发、未经药物治疗的 MDD 患者的临床变量之间的关联。
与健康对照组（HC）（N=19）相比，MDD 组（N=15）的血浆色氨酸和犬尿氨酸水平显著降低，而血浆色氨酸是识别 MDD 组的显著生物标志物（曲线下面积=0.740）。MDD 组中，血清高密度脂蛋白胆固醇（HDL-C）水平较低是抑郁严重程度的预测生物标志物（R=0.444）。有趣的是，抑郁症状与血浆色氨酸-犬尿氨酸和脂质相关代谢物的相关性各不相同。此外，MDD 组中血浆色氨酸-犬尿氨酸代谢物与胆固醇酯（CEs）显著相关，但在 HC 组中没有相关性。
本研究样本量较小，且未使用多重检验校正。
这是第一项表明不仅色氨酸-犬尿氨酸代谢物，而且 HDL-C 和 CEs 也是初发、未经药物治疗的 MDD 患者重要血液生物标志物的研究。本研究为抑郁症的临床实践中的早期干预提供了新的视角，需要进一步的临床研究，特别是大规模前瞻性研究。
