Department of Public Health, section Epidemiology, University of Copenhagen, Copenhagen, Denmark; Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark; The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam, The Netherlands; Amsterdam UMC, Vrije Universiteit Amsterdam, GGZ inGeest / Department of Psychiatry and Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
Psychoneuroendocrinology. 2019 Jan;99:20-27. doi: 10.1016/j.psyneuen.2018.08.029. Epub 2018 Aug 24.
Different biological mechanisms may underlie depression beginning in early life (early-onset) and depression beginning later in life (late-onset). Although the relation between inflammation and depression has been studied extensively, the distinct role of inflammation in early and late-onset depression in older patients has not been addressed before. In the cross-sectional part of this study, we explored differences in levels of circulating inflammatory markers and cytokine levels in lipopolysaccharide (LPS) stimulated whole blood between older subjects with a late-life onset depression (≥60 years) and older subjects with an early-onset depression (<60 years). Secondly, in a 2-year follow-up study, we examined if circulating and stimulated inflammatory markers influenced the change in Inventory of Depressive Symptomatology (IDS) scores, and if this relation was different for early- and late-onset depression.
The study was part of the Netherlands Study of Depression in Older Persons (NESDO). We included 350 patients, all aged 60 and older, with a depressive episode in the previous 6 months: 119 with a late-onset depression and 231 with an early-onset depression. Blood samples were collected and CRP, IL-6, NGAL, GDF15, and, LPS plasma levels were determined and whole blood was LPS stimulated and cytokine levels IL-1β, IL-6, TNFα, IFNγ, IL-10, and IL-1 receptor antagonist (IL-1ra) were determined.
After adjustment for demographics, health indicators, and medication use, increased plasma CRP levels were more strongly associated with late-onset depression than early-onset depression (OR [95% CI]: 1.43 [1.05-1.94]). In the longitudinal analyses, higher circulating IL-6 levels were associated with a significantly slower decline in IDS scores in the crude and the adjusted models (p ≤ 0.027). This relation was not different between late- and early-onset depression. Other circulating and stimulated inflammatory markers were not associated with late- and/or early-onset depression.
This study provides preliminary evidence that low-grade inflammation is more strongly associated with late-onset than early-onset depression in older adults, suggesting a distinct inflammatory etiology for late-onset depression. Cytokine production capacity did not distinguish between early- and late-onset depression.
不同的生物学机制可能导致生命早期（早发性）和生命后期（晚发性）开始出现抑郁。虽然炎症与抑郁之间的关系已经得到了广泛的研究，但炎症在老年患者中早发性和晚发性抑郁中的独特作用尚未得到解决。在这项研究的横断面部分，我们探讨了老年患者中晚发性抑郁症（≥60 岁）和早发性抑郁症（<60 岁）患者循环炎症标志物和脂多糖（LPS）刺激全血中细胞因子水平之间的差异。其次，在为期 2 年的随访研究中，我们检查了循环和刺激的炎症标志物是否影响抑郁症状量表（IDS）评分的变化，以及这种关系是否因早发性和晚发性抑郁而不同。
该研究是荷兰老年抑郁症研究（NESDO）的一部分。我们纳入了 350 名年龄在 60 岁及以上、过去 6 个月内有抑郁发作的患者：119 名晚发性抑郁症患者和 231 名早发性抑郁症患者。采集血样，测定 CRP、IL-6、NGAL、GDF15 和 LPS 血浆水平，并刺激全血，测定细胞因子水平 IL-1β、IL-6、TNFα、IFNγ、IL-10 和 IL-1 受体拮抗剂（IL-1ra）。
调整人口统计学、健康指标和用药情况后，与早发性抑郁症相比，LPS 血浆 CRP 水平升高与晚发性抑郁症的相关性更强（OR [95%CI]：1.43 [1.05-1.94]）。在纵向分析中，在未调整和调整模型中，较高的循环 IL-6 水平与 IDS 评分的下降速度显著减慢相关（p≤0.027）。这种关系在晚发性和早发性抑郁症之间没有差异。其他循环和刺激的炎症标志物与晚发性和/或早发性抑郁症无关。
本研究初步表明，在老年人群中，低度炎症与晚发性抑郁的相关性强于早发性抑郁，提示晚发性抑郁的炎症发病机制不同。细胞因子产生能力不能区分早发性和晚发性抑郁。
