Department of Medical Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey.
Department of Psychiatry, Faculty of Medicine, Gazi University, Ankara, Turkey.
J Neural Transm (Vienna). 2022 Dec;129(12):1513-1526. doi: 10.1007/s00702-022-02553-x. Epub 2022 Nov 5.
The kynurenine pathway (KP) and inflammation are substantial in depression pathogenesis. Although there is a crosstalk between the KP, inflammation, and neurotrophic factors, few studies examine these topics together. Novel medications may be developed by clarifying dysregulations related to inflammation, KP, and neurotrophic factors in treatment-resistant depression (TRD). We aimed to evaluate the serum levels of KP metabolites, proinflammatory biomarkers, and brain-derived neurotrophic factor (BDNF) in healthy controls (HC) and the patients with TRD whose followed up with three different treatments. Moreover, the effect of electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) on biomarkers was investigated. Study groups comprised a total of 30 unipolar TRD patients consisting of three separate patient groups (ECT = 8, rTMS = 10, pharmacotherapy = 12), and 9 HC. The decision to administer only pharmacotherapy or ECT/rTMS besides pharmacotherapy was given independently of this research by psychiatrists. Blood samples and symptom scores were obtained three times for patients. At baseline, quinolinic acid (QUIN) was higher in the patients with TRD compared to HC, whereas picolinic acid (PIC), PIC/QUIN, and PIC/3-hydroxykynurenine were lower. Baseline interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) were higher in nonresponders and non-remitters. ECT had an acute effect on cytokines. In the rTMS group, tumor necrosis factor-α (TNF-α) decreased in time. PIC, QUIN, and aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) enzyme may play a role in TRD pathogenesis, and have diagnostic potential. rTMS and ECT have modulatory effects on low-grade inflammation seen in TRD. Baseline inflammation severity is predictive in terms of response and remission in depression.
犬尿酸途径 (KP) 和炎症在抑郁症发病机制中起重要作用。虽然 KP、炎症和神经营养因子之间存在相互作用，但很少有研究将这些主题一起研究。通过阐明与治疗抵抗性抑郁症 (TRD) 相关的炎症、KP 和神经营养因子的失调，可能会开发出新的药物。我们旨在评估健康对照组 (HC) 和接受三种不同治疗的 TRD 患者的 KP 代谢物、促炎生物标志物和脑源性神经营养因子 (BDNF) 的血清水平。此外，还研究了电惊厥治疗 (ECT) 和重复经颅磁刺激 (rTMS) 对生物标志物的影响。研究组共包括 30 名单相 TRD 患者，分为三个单独的患者组（ECT=8，rTMS=10，药物治疗=12）和 9 名 HC。是否仅给予药物治疗或药物治疗外加 ECT/rTMS 的决定是由精神科医生独立于本研究做出的。患者的血液样本和症状评分均采集了三次。在基线时，TRD 患者的 QUIN 高于 HC，而 PIC、PIC/QUIN 和 PIC/3-羟基犬尿氨酸则较低。基线时，反应不良者和无缓解者的白细胞介素-6 (IL-6) 和高敏 C 反应蛋白 (hsCRP) 较高。ECT 对细胞因子有急性作用。rTMS 组中，TNF-α 随时间减少。PIC、QUIN 和氨基羧基脒半醛脱羧酶 (ACMSD) 酶可能在 TRD 发病机制中起作用，具有诊断潜力。rTMS 和 ECT 对 TRD 中所见的低水平炎症具有调节作用。基线炎症严重程度可预测抑郁的反应和缓解。
