Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
J Affect Disord. 2020 Jul 1;272:1-7. doi: 10.1016/j.jad.2020.03.145. Epub 2020 Apr 5.
Replicated evidence has documented elevated levels of pro-inflammatory cytokines in populations with major depressive disorder (MDD). However, childhood trauma, a risk factor for MDD, has been separately shown to also impact inflammatory systems; its potential moderating effect on inflammation in MDD has been less frequently investigated.
We systematically searched the PubMed, Google Scholar, Scopus, Web of Science, and PsycINFO databases between database inception to June 19th, 2019 using the search string: (Childhood trauma or Adverse childhood experiences or childhood abuse or childhood rape or physical abuse or emotional abuse) AND (Inflammation or inflammatory cytokines or interleukin-6 or tumor necrosis factor-alpha or c-reactive protein) AND (Major Depressive Disorder or Depression).
We identified nine articles that evaluated inflammatory biomarkers in MDD populations with adverse childhood experiences (ACE). Eight articles evaluated IL-6, three articles evaluated CRP, and five articles evaluated TNF-α. The strongest effects were observed for IL-6; six studies reported significantly elevated levels of IL-6 in MDD and ACE patients compared to healthy controls and/or MDD-only populations. Meanwhile, only three studies found TNF-α to be significantly elevated in the MDD and ACE cohort. In contrast, MDD-ACE populations did not exhibit significantly elevated CRP.
The methodological heterogeneity amongst studies was very high.
The current review suggests that MDD and ACE subpopulations present elevated levels of IL-6 compared to MDD-only and healthy control populations. Therefore, research should consider whether elevated inflammation in MDD is just an epiphenomenon of previous ACE and whether MDD-ACE subgroups are more likely to respond to immune-inflammatory targeted intervention.
已有大量证据表明，患有重度抑郁症（MDD）的人群中促炎细胞因子水平升高。然而，作为 MDD 的风险因素之一的童年创伤也被证明会对炎症系统产生影响；其对 MDD 中炎症的潜在调节作用则较少受到关注。
我们系统地检索了 PubMed、Google Scholar、Scopus、Web of Science 和 PsycINFO 数据库，检索时间从数据库建立至 2019 年 6 月 19 日，使用的检索词为：（童年创伤或不良童年经历或儿童虐待或儿童性侵犯或身体虐待或情感虐待）和（炎症或炎症细胞因子或白细胞介素-6 或肿瘤坏死因子-α或 C 反应蛋白）和（重度抑郁症或抑郁症）。
我们共确定了 9 篇评估有不良童年经历（ACE）的 MDD 人群中炎症生物标志物的文章。8 篇文章评估了白细胞介素-6（IL-6），3 篇文章评估了 C 反应蛋白（CRP），5 篇文章评估了肿瘤坏死因子-α（TNF-α）。观察到的最强影响是白细胞介素-6（IL-6）；有 6 项研究报告称，与健康对照组和/或仅有 MDD 的人群相比，MDD 和 ACE 患者的 IL-6 水平显著升高。同时，只有 3 项研究发现 MDD 和 ACE 队列中的 TNF-α水平显著升高。相比之下，MDD-ACE 人群的 CRP 没有显著升高。
研究之间的方法学异质性非常高。
本综述表明，与仅有 MDD 和健康对照组人群相比，MDD 和 ACE 亚群的 IL-6 水平升高。因此，研究应该考虑 MDD 中的炎症是否仅仅是 ACE 之前的一种表现，以及 MDD-ACE 亚组是否更有可能对免疫炎症靶向干预产生反应。
