BACKGROUND Depression has been associated with low-grade elevation of plasma cytokines (e.g. interleukin-6, IL-6; tumor necrosis factor alpha, TNFα) in both cross-sectional and longitudinal studies in adults. Preclinical and clinical studies also suggest that IL-6 and TNFα elevation are associated with anhedonia. However, few studies have examined longitudinal relationships between cytokines and depression/anhedonia in clinically depressed samples, particularly adolescents. METHODS Thirty-six adolescents with a depressive disorder receiving standard-of-care community treatment were assessed at a baseline and a follow-up timepoint. Self-report and clinical measures of depression and anhedonia, along with plasma IL-6 and TNFα levels, were obtained at both timepoints. Baseline cytokine measures were examined in association with baseline and follow-up clinical measures. On an exploratory basis, change in clinical measures over time was examined in relation to change in cytokine levels over time. RESULTS Higher baseline TNFα levels predicted higher follow-up depression severity after approximately four months (controlling for baseline depression). Higher baseline TNFα levels also associated positively with baseline anhedonia and predicted higher anhedonia at follow-up (controlling for baseline anhedonia). No association was found between change in clinical measures and change in cytokine levels over time. CONCLUSIONS Among adolescents receiving standard-of-care community treatment for depression, higher levels of TNFα predicted greater depressive symptoms at 4-month follow-up, suggesting this cytokine may be used to help identify patients in need of more intensive treatment. Elevated TNFα levels were also associated with concurrent and future anhedonia symptoms, suggesting a specific mechanism in which TNFα affects depression trajectories. Future studies should examine the relationships between cytokine levels and depression/anhedonia symptoms at multiple timepoints in larger cohorts of depressed adolescents.

中文翻译：

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抑郁青少年细胞因子、抑郁和快感缺失的纵向关系

背景技术在成人的横断面和纵向研究中，抑郁症与血浆细胞因子（例如白细胞介素6、IL-6；肿瘤坏死因子α、TNFα）的低度升高有关。临床前和临床研究还表明，IL-6 和 TNFα 升高与快感缺乏有关。然而，很少有研究在临床抑郁样本中，特别是青少年中，检验细胞因子与抑郁/快感缺乏之间的纵向关系。方法 对 36 名接受标准护理社区治疗的抑郁症青少年进行基线和随访时间点评估。在两个时间点都获得了抑郁症和快感缺乏的自我报告和临床测量，以及血浆 IL-6 和 TNFα 水平。基线细胞因子测量与基线和后续临床测量相关联进行检查。在探索性的基础上，检查了临床指标随时间的变化与细胞因子水平随时间变化的关系。结果 较高的基线 TNFα 水平预示着大约四个月后后续抑郁症的严重程度较高（控制基线抑郁症）。较高的基线 TNFα 水平也与基线快感缺乏呈正相关，并预测随访时会出现较高的快感缺乏（控制基线快感缺乏）。随着时间的推移，临床测量的变化与细胞因子水平的变化之间没有发现关联。结论 在接受标准护理社区抑郁症治疗的青少年中，4 个月随访时较高水平的 TNFα 预示着更严重的抑郁症状，表明这种细胞因子可用于帮助识别需要更强化治疗的患者。TNFα 水平升高也与同时发生和未来的快感缺乏症状相关，这表明 TNFα 影响抑郁轨迹的特定机制。未来的研究应该在更大的抑郁青少年群体中检查多个时间点的细胞因子水平与抑郁/快感缺乏症状之间的关系。