Circulating versus lipopolysaccharide-induced inflammatory markers as correlates of subthreshold depressive symptoms in older adults

<b>Objectives:</b> Circulating cytokines have been associated with depression, but their detection has limitations, which may be overcome by direct detection of intracellular cytokines (ICCs) after lipopolysaccharide (LPS) stimulation <i>in vitro</i>. This study compared circulating versus LPS-induced inflammatory markers as correlates of subthreshold depressive symptoms. <b>Methods:</b> Secondary data analysis of a cross-sectional insomnia study in healthy community-dwelling older adults was conducted. In 117 participants (≥55 years), plasma tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP) and <i>in vitro</i> LPS-induced monocyte production of IL-6 and TNF-α were assayed. Depressive symptoms were assessed using the clinician-rated Inventory of Depressive Symptomatology (IDS-C). Multivariate linear regression was conducted to test the associations between inflammatory markers and subthreshold depressive symptoms in the entire sample as well as in subgroups stratified into higher and lower inflammation levels. <b>Results:</b> LPS-induced TNF-α (adjusted <i>β</i> = 0.28, <i>p = </i>.04), IL-6 (0.29, <i>p = </i>.03) and TNF-α + IL-6 (0.43, <i>p = </i>.001) significantly positively correlated with subthreshold depressive symptoms only in higher inflammation subgroups. No circulating biomarkers positively correlated in any subgroups. In the entire sample, no biomarkers were significantly associated with subthreshold depressive symptoms. <b>Conclusions:</b> LPS-induced cytokines may be more sensitive correlates of subthreshold depressive symptoms than circulating cytokines, particularly in older adults with higher systemic inflammation. <b>Clinical Trials Registry:</b> ClinicalTrials.gov NCT00280020.

**研究目的：** 循环细胞因子与抑郁症存在关联，但现有检测手段存在局限性，而通过脂多糖（lipopolysaccharide, LPS）体外（in vitro）刺激后直接检测细胞内细胞因子（intracellular cytokines, ICCs）或可突破此类局限。本研究对比了循环炎症标志物与脂多糖诱导的炎症标志物作为亚阈值抑郁症状关联指标的效能。
**研究方法：** 本研究针对一项纳入社区健康老年群体的横断面失眠研究开展二次数据分析。共纳入117名年龄≥55岁的受试者，对其血浆肿瘤坏死因子-α（tumour necrosis factor-α, TNF-α）、白细胞介素-6（interleukin-6, IL-6）、C反应蛋白（C-reactive protein, CRP），以及体外（in vitro）脂多糖诱导的单核细胞产生的IL-6与TNF-α进行了检测。采用临床医师评定版抑郁症状量表（Inventory of Depressive Symptomatology, IDS-C）评估抑郁症状。通过多元线性回归分析，检验全样本以及按全身炎症水平分层的高低炎症亚组中，炎症标志物与亚阈值抑郁症状之间的关联。
**研究结果：** 仅在高炎症亚组中，脂多糖诱导的TNF-α（校正后β=0.28，p=0.04）、IL-6（校正后β=0.29，p=0.03）以及TNF-α与IL-6联合指标（校正后β=0.43，p=0.001）与亚阈值抑郁症状呈显著正相关。所有亚组中均未观察到循环生物标志物与抑郁症状存在正相关关联。全样本分析中，未发现任何生物标志物与亚阈值抑郁症状存在显著关联。
**研究结论：** 相较于循环细胞因子，脂多糖诱导的细胞因子或可作为亚阈值抑郁症状更为敏感的关联指标，这一效应在全身炎症水平较高的老年群体中尤为显著。
**临床试验注册信息：** ClinicalTrials.gov 编号NCT00280020。