Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
Department of Psychiatry, Taipei Veterans General Hospital, Taiwan No. 201, Shi-Pai Rd, Section 2, Taipei 112, Taiwan.
J Clin Psychiatry. 2018 Jan/Feb;79(1). doi: 10.4088/JCP.17m11540.
The relationship between severe inflammation and clinical depression in the context of major medical illnesses has been addressed, but the relationship between inflammation caused by mild infections and clinical depression is unclear. We aimed to examine whether a history of repeated low-grade infections (RLGI) in medically healthy subjects (MHS) could increase their vulnerability to major depressive disorder (MDD) (ICD-9-CM) and whether RLGI could be associated with higher resistance to antidepressants in those developing MDD.
A nationwide, population-based cohort study (January 1996 to December 2011) was conducted for MHS with and without a history of RLGI. The rates of MDD during an up to 8-year follow-up period were compared between the 2 groups in 2 independent cohorts. The stratified responses to adequate antidepressant trials, including easy-to-treat (ETT) and difficult-to-treat (DTT) responses, were also compared in the MDD patients.
During the follow-up, the 2 cohorts consistently revealed that the RLGI(+) (ie, high-inflammation; n = 727) group had a significantly higher chance of developing MDD over time than the RLGI(-) (ie, low-inflammation; n = 443) group: Cox proportional hazards regression models showed that the hazard ratio associated with a history of RLGI was 1.369 to 1.911 (P < .001), after adjusting for confounding factors. The RLGI(+) group was consistently associated with a higher likelihood of DTT responses than was the RLGI(-) group (Cohort-2002: 11.5% vs 7.6%; Cohort-2004: 11.8% vs 4.3%; P < .05 by Wald χ² tests in both cohorts).
This is the first large-scale retrospective cohort study to report a reliable temporal association between a history of RLGI and subsequent diagnosis of MDD and poor responses to antidepressants in 2 independent cohorts. Our data support the view that repeated mild infections play a role in the pathophysiology of MDD and antidepressant-resistant depression.
在重大疾病的背景下，严重炎症与临床抑郁症之间的关系已得到研究，但轻度感染引起的炎症与临床抑郁症之间的关系尚不清楚。我们旨在研究在无重大疾病的健康受试者（MHS）中，反复发生轻度感染（RLGI）是否会增加他们患重度抑郁症（MDD）（ICD-9-CM）的易感性，以及 RLGI 是否与那些发生 MDD 的患者对抗抑郁药的反应较差有关。
我们进行了一项全国性的基于人群的队列研究（1996 年 1 月至 2011 年 12 月），其中包括有和无 RLGI 病史的 MHS。在 2 个独立队列中，比较了长达 8 年的随访期间 MDD 的发病率。还比较了 MDD 患者对充分的抗抑郁药试验的分层反应，包括容易治疗（ETT）和困难治疗（DTT）反应。
在随访期间，2 个队列均显示，RLGI（+）（即炎症水平高；n=727）组随着时间的推移发展为 MDD 的可能性明显高于 RLGI（-）（即炎症水平低；n=443）组：Cox 比例风险回归模型显示，调整混杂因素后，RLGI 病史相关的风险比为 1.369 至 1.911（P<.001）。RLGI（+）组与 DTT 反应的可能性更高相关，而 RLGI（-）组则不然（队列 2002：11.5%比 7.6%；队列 2004：11.8%比 4.3%；通过 Wald χ²检验在两个队列中均有统计学差异，P<.05）。
这是第一项大规模回顾性队列研究，报告了 RLGI 病史与随后的 MDD 诊断以及 2 个独立队列中对抗抑郁药反应不佳之间存在可靠的时间关联。我们的数据支持这样一种观点，即反复发生的轻度感染在 MDD 和抗抑郁药难治性抑郁症的病理生理学中起作用。
