背景:炎症已成为重度抑郁症(MDD)的重要病理机制。NLRP3是维持免疫平衡的关键炎症通路。最近,临床前证据表明,ResolvinD1可能为抗抑郁治疗提供新的选择,因为它通过抑制神经炎症具有保护作用.然而,它们在青少年抑郁症的诊断和治疗评估中是否具有临床价值尚不清楚.
方法:48名未经治疗的首发青少年中重度抑郁症患者,以及30名健康青少年(HC,年龄和性别匹配),参加了这项研究。他们的年龄范围为13至18(15.75±1.36)岁。患者接受氟西汀治疗6-8周。HDRS-17用于评估抑郁症状的严重程度。两组在基线和患者抗抑郁治疗后的时间点收集静脉血样本。血清RvD1,NLRP3,IL-1β,在氟西汀治疗前后,通过酶联免疫吸附测定(ELISA)测量IL-18和IL-4。
结果:与健康青少年相比,MDD青少年血清RvD1和抗炎细胞因子IL-4水平显著升高,但NLRP3、IL-1β、两组之间的IL-18。同时,RvD1(正)和IL-4(负)与调整年龄后的症状严重程度(HDRS-17评分)相关,性别,BMI。有趣的是,氟西汀治疗显著降低血清RvD1、NLRP3、IL-1β、和IL-18在青少年MDD中,但IL-4水平相对于基线增加。此外,我们观察到血清RvD1水平可能是抑郁症和健康青少年的一个很好的区分指标.
结论:我们的研究首次比较了青少年MDD和HCs之间的RvD1和NLRP3。我们发现青少年MDD中RvD1的反应性增加具有新颖而重要的贡献。我们的结果表明青少年MDD患者存在炎症消退不平衡,表明RvD1可能是诊断和治疗青少年MDD的理想生物标志物。
BACKGROUND: Inflammation has become a critical pathological mechanism of Major Depressive Disorder (MDD). NLRP3 is a critical inflammatory pathway to maintain the immune balance. Recently, preclinical evidence showed that Resolvin D1 might potentially offer a new option for antidepressant treatment due to its protective effects through the inhibition of neuroinflammation. However, whether they have clinical value in the diagnosis and treatment evaluation of adolescent depression was unclear.
METHODS: Forty-eight untreated first-episode adolescent patients with moderate to severe major depressive disorder, as well as 30 healthy adolescents (HCs, age and gender-matched), were enrolled for this study. Their ages ranged from 13 to 18 (15.75 ± 1.36) years. The patients were treated with fluoxetine for 6-8 weeks. HDRS-17 was used to evaluate the severity of depressive symptoms. Venous blood samples were collected at baseline for the two groups and at the time-point of post-antidepressant treatment for the patients. Serum concentrations of RvD1, NLRP3, IL-1β, IL-18, and IL-4 were measured by enzyme-linked immunosorbent assays (ELISA) pre- and post-fluoxetine treatment.
RESULTS: Serum levels of RvD1 and anti-inflammatory cytokine IL-4 were significantly elevated in adolescents with MDD compared to healthy adolescents, but no significant difference in NLRP3, IL-1β, and IL-18 between the two groups. Meanwhile, RvD1 (positively) and IL-4 (negatively) were correlated with the severity of symptoms (HDRS-17 scores) after adjusting age, gender, and BMI. Interestingly, fluoxetine treatment significantly reduced the serum levels of RvD1, NLRP3, IL-1β, and IL-18 in MDD adolescents but increased the levels of IL-4 relative to baseline. Furthermore, we observed that serum levels of RvD1 might be an excellent distinguishing indicator for depression and healthy adolescents.
CONCLUSIONS: Our study is the first to compare RvD1 and NLRP3 between adolescent MDD and HCs. Our findings of reactive increase of RvD1 in adolescent MDD comprised a novel and critical contribution. Our results showed the presence of inflammation resolution unbalanced in adolescents with MDD and indicated that RvD1 might be an ideal biomarker for diagnosing and treating adolescent MDD.