Öztürk Masum, Yalın Sapmaz Şermin, Kandemir Hasan, Taneli Fatma, Aydemir Ömer
Department of Child and Adolescent Psychiatry, Kızıltepe State Hospital, Mardin, Turkey.
Faculty of Medicine, Department of Child and Adolescent Psychiatry, Manisa Celal Bayar University, Manisa, Turkey.
Int J Clin Pract. 2021 Apr;75(4):e13739. doi: 10.1111/ijcp.13739. Epub 2020 Oct 27.
The biological mechanisms underlying major depressive disorder (MDD) are not yet sufficiently understood. The kynurenine pathway has been proposed to play a key role between peripheral inflammation and alterations in the central nervous system. This is because of reduced usability of tryptophan (TRP) and production of oxygen radicals and highly potent neurotoxic agents in this pathway.
In this study, we aimed to compare the metabolites of the serum kynurenine pathway (tryptophan, kynurenine, quinolinic acid and kynurenic acid) and IFN-γ, IL-6, IL-1β and high-sensitivity C-reactive protein (hsCRP) levels in patients with major depressive disorder and in healthy controls and to evaluate the relationship between cytokine levels and the functioning of the kynurenine pathway.
Clinical and biochemical data from the patients were obtained and assessed in a cross-sectional design. Serum samples were analysed for IL-6, IL-1β, interferon (IFN)-γ, tryptophan (TRP), quinolinic acid (QUIN), kynurenic acid (KYNA) and kynurenine (Kyn) levels by the enzyme-linked immunosorbent assay. hsCRP test was analysed by the immunoturbidimetric method.
In total, 48 adolescent patients with major depressive disorder (no drug use) and 31 healthy controls were included in the study. TRP levels were observed to be significantly lower in patients with MDD than in healthy controls (P = .046); the Kyn/TRP ratio was significantly higher in patients with MDD than in healthy controls (P = .032); the levels of QUIN were significantly higher in patients with MDD than in healthy controls (P = .003). No significant difference was found between the groups in terms of other kynurenine metabolites and cytokines levels.
These results suggest that the Kyn and related molecular pathways may play a role in the pathophysiology of MDD. The most important finding was the increased level of QUIN, which has a neurotoxic effect, in the kynurenine pathway.
重度抑郁症（MDD）潜在的生物学机制尚未得到充分理解。有人提出犬尿氨酸途径在周围炎症与中枢神经系统改变之间起关键作用。这是因为该途径中色氨酸（TRP）可用性降低以及氧自由基和高效神经毒性剂的产生。
在本研究中，我们旨在比较重度抑郁症患者与健康对照者血清犬尿氨酸途径的代谢产物（色氨酸、犬尿氨酸、喹啉酸和犬尿酸）以及IFN-γ、IL-6、IL-1β和高敏C反应蛋白（hsCRP）水平，并评估细胞因子水平与犬尿氨酸途径功能之间的关系。
以横断面设计获取并评估患者的临床和生化数据。通过酶联免疫吸附测定法分析血清样本中的IL-6、IL-1β、干扰素（IFN）-γ、色氨酸（TRP）、喹啉酸（QUIN）、犬尿酸（KYNA）和犬尿氨酸（Kyn）水平。hsCRP检测采用免疫比浊法进行分析。
本研究共纳入48例未使用药物的青少年重度抑郁症患者和31名健康对照者。观察到MDD患者的TRP水平显著低于健康对照者（P = 0.046）；MDD患者的Kyn/TRP比值显著高于健康对照者（P = 0.032）；MDD患者的QUIN水平显著高于健康对照者（P = 0.003）。在其他犬尿氨酸代谢产物和细胞因子水平方面，两组之间未发现显著差异。
这些结果表明Kyn及相关分子途径可能在MDD的病理生理学中起作用。最重要的发现是犬尿氨酸途径中具有神经毒性作用的QUIN水平升高。
