Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland; Department of Psychiatry, St. Patrick's University Hospital, Trinity College Dublin, Dublin, Ireland.
Central Nervous System Disease Research, Boehringer Ingelheim Pharma GmbH + Co. KG, Birkendorferstrabe 65, Biberach a.d. Riss, Germany.
Brain Behav Immun. 2020 Jan;83:153-162. doi: 10.1016/j.bbi.2019.10.005. Epub 2019 Oct 10.
Tryptophan and kynurenine pathway (KP) metabolites are implicated in the pathophysiology of depression. We aimed to investigate their plasma concentrations in medicated patients with depression (n = 94) compared to age- and sex-matched healthy controls (n = 57), and in patients with depression after electroconvulsive therapy (ECT) in a real-world clinical setting, taking account of co-variables including ECT modality and heterogenous psychopathology. Depression severity was assessed using the Hamilton Depression Rating Scale (HAM-D24). Tryptophan (TRP) and kynurenine (KYN) metabolite concentrations [anthranilic acid (AA), 3-hydroxyanthranilic acid (3HAA), picolinic acid (PA), kynurenic acid (KYNA), and xanthurenic acid (XA)] and KYNA/KYN and KYNA/quinolinic acid (QUIN) ratios were lower in patients compared to controls. For the total group there was no significant change in KP metabolites post-ECT or correlations with mood ratings. However, improvements in mood score were correlated with increased KYN, 3-hydroxykynurenine (3HK), 3HAA, QUIN, and KYN/TRP in a subgroup of unipolar depressed patients. Additionally, in remitters baseline KYN, 3HK, and QUIN were associated with baseline HAM-D24 scores, and changes in 3HK and 3HAA concentrations post-ECT correlated with improvement in mood. KYN, KYNA, AA, 3HK, XA, PA, and QUIN were increased in a smaller 3-month follow-up group (n = 19) compared to pre-ECT concentrations. Overall, the results indicate that ECT mobilizes the KP, where a moderate association between selected metabolites and treatment response in unipolar depressed patients is evident.
色氨酸和犬尿氨酸途径（KP）代谢物与抑郁症的病理生理学有关。我们旨在研究接受药物治疗的抑郁症患者（n=94）与年龄和性别匹配的健康对照组（n=57）之间的血浆浓度，并在现实临床环境中研究电抽搐治疗（ECT）后抑郁症患者的浓度，同时考虑包括ECT 方式和异质精神病理学在内的协变量。使用汉密尔顿抑郁评定量表（HAM-D24）评估抑郁严重程度。与对照组相比，患者的色氨酸（TRP）和犬尿氨酸（KYN）代谢物浓度[邻氨基苯甲酸（AA）、3-羟基邻氨基苯甲酸（3HAA）、吡啶酸（PA）、犬尿氨酸（KYNA）和黄尿酸（XA）]和 KYNA/KYN 和 KYNA/喹啉酸（QUIN）比值较低。对于整个组，ECT 后 KP 代谢物没有明显变化，也与情绪评分没有相关性。然而，在单相抑郁患者亚组中，情绪评分的改善与 KYN、3-羟基犬尿氨酸（3HK）、3HAA、QUIN 和 KYN/TRP 的增加相关。此外，在缓解者中，基线 KYN、3HK 和 QUIN 与基线 HAM-D24 评分相关，ECT 后 3HK 和 3HAA 浓度的变化与情绪改善相关。与 ECT 前浓度相比，在较小的 3 个月随访组（n=19）中，KYN、KYNA、AA、3HK、XA、PA 和 QUIN 增加。总的来说，这些结果表明 ECT 可动员 KP，在单相抑郁患者中，一些代谢物与治疗反应之间存在中等相关性。
