Almutabagani Lara F, Almanqour Raghad A, Alsabhan Jawza F, Alhossan Abdulaziz M, Alamin Maha A, Alrajeh Haya M, Alonazi Asma S, El-Malky Ahmed M, Alrasheed Nouf M
PharmD. Program, College of Pharmacy, King Saud University, Riyadh P.O. Box 145111, Saudi Arabia.
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh P.O. Box 145111, Saudi Arabia.
Neurol Int. 2023 Jan 16;15(1):100-120. doi: 10.3390/neurolint15010009.
The aim of this study was to investigate the relationship between treatment-resistant depression (TRD) and inflammation in humans and experimental models. For the human study, a retrospective cohort study was conducted with 206 participants; half were on antidepressants for major depressive disorder. The patients were divided into healthy and depressed groups. Inflammation was assessed based on the values of the main inflammatory biomarkers (CRP, WBC and ESR). For the animal experiments, 35 adult male Wistar rats were assigned to stressed and non-stressed groups. Inflammation and stress were induced using lipopolysaccharide and chronic unpredictable mild stress. A 10 mg/kg intraperitoneal injection of fluoxetine (FLX), a known antidepressant, was simultaneously administered daily for 4 weeks. Behavioral tests were performed. The plasma levels of inflammatory and stress biomarkers were measured and were significantly higher in the stressed and non-responsive groups in both studies. This study provides evidence of the link between inflammation and TRD. We further observed a possible link via the Phosphorylated Janus Kinase 2 and Phosphorylated Signal Transducer and Activator of Transcription 3 (P-JAK2/P-STAT3) signaling pathway and found that chronic stress and high inflammation hinder the antidepressant effects of FLX. Thus, non-response to antidepressants could be mitigated by treating inflammation to improve the antidepressant effect in patients with TRD.
本研究的目的是调查难治性抑郁症（TRD）与人类及实验模型中炎症之间的关系。对于人体研究，开展了一项针对206名参与者的回顾性队列研究；其中一半参与者正在服用治疗重度抑郁症的抗抑郁药。将患者分为健康组和抑郁组。基于主要炎症生物标志物（CRP、白细胞和血沉）的值评估炎症情况。对于动物实验，将35只成年雄性Wistar大鼠分为应激组和非应激组。使用脂多糖和慢性不可预测轻度应激诱导炎症和应激。每天同时腹腔注射10mg/kg已知的抗抑郁药氟西汀（FLX），持续4周。进行行为测试。在两项研究中，均测量了炎症和应激生物标志物的血浆水平，且在应激组和无反应组中显著更高。本研究提供了炎症与TRD之间存在关联的证据。我们进一步观察到通过磷酸化的Janus激酶2和磷酸化的信号转导子及转录激活子3（P-JAK2/P-STAT3）信号通路存在可能的联系，并发现慢性应激和高度炎症会阻碍FLX的抗抑郁作用。因此，通过治疗炎症来改善TRD患者的抗抑郁效果，可能会减轻对抗抑郁药的无反应情况。
