Department of Psychiatry,University of Cambridge,UKandCambridgeshire and Peterborough NHS Foundation Trust,Cambridge,UK.
Institute of Health & Wellbeing,University of Glasgow,Glasgow,UK.
Br J Psychiatry. 2019 Jan;214(1):11-19. doi: 10.1192/bjp.2018.66. Epub 2018 May 16.
C-reactive protein (CRP) is a candidate biomarker for major depressive disorder (MDD), but it is unclear how peripheral CRP levels relate to the heterogeneous clinical phenotypes of the disorder.AimTo explore CRP in MDD and its phenotypic associations.
We recruited 102 treatment-resistant patients with MDD currently experiencing depression, 48 treatment-responsive patients with MDD not currently experiencing depression, 48 patients with depression who were not receiving medication and 54 healthy volunteers. High-sensitivity CRP in peripheral venous blood, body mass index (BMI) and questionnaire assessments of depression, anxiety and childhood trauma were measured. Group differences in CRP were estimated, and partial least squares (PLS) analysis explored the relationships between CRP and specific clinical phenotypes.
Compared with healthy volunteers, BMI-corrected CRP was significantly elevated in the treatment-resistant group (P = 0.007; Cohen's d = 0.47); but not significantly so in the treatment-responsive (d = 0.29) and untreated (d = 0.18) groups. PLS yielded an optimal two-factor solution that accounted for 34.7% of variation in clinical measures and for 36.0% of variation in CRP. Clinical phenotypes most strongly associated with CRP and heavily weighted on the first PLS component were vegetative depressive symptoms, BMI, state anxiety and feeling unloved as a child or wishing for a different childhood.
CRP was elevated in patients with MDD, and more so in treatment-resistant patients. Other phenotypes associated with elevated CRP included childhood adversity and specific depressive and anxious symptoms. We suggest that patients with MDD stratified for proinflammatory biomarkers, like CRP, have a distinctive clinical profile that might be responsive to second-line treatment with anti-inflammatory drugs.Declaration of interestS.R.C. consults for Cambridge Cognition and Shire; and his input in this project was funded by a Wellcome Trust Clinical Fellowship (110049/Z/15/Z). E.T.B. is employed half time by the University of Cambridge and half time by GlaxoSmithKline; he holds stock in GlaxoSmithKline. In the past 3 years, P.J.C. has served on an advisory board for Lundbeck. N.A.H. consults for GlaxoSmithKline. P.d.B., D.N.C.J. and W.C.D. are employees of Janssen Research & Development, LLC., of Johnson & Johnson, and hold stock in Johnson & Johnson. The other authors report no financial disclosures or potential conflicts of interest.
C 反应蛋白（CRP）是重度抑郁症（MDD）的候选生物标志物，但外周 CRP 水平与该疾病的异质临床表型之间的关系尚不清楚。目的：探讨 CRP 在 MDD 中的作用及其与表型的关系。
我们招募了 102 名正在接受治疗的 MDD 患者（治疗抵抗组）、48 名未出现抑郁症状的 MDD 患者（治疗缓解组）、48 名未接受药物治疗的抑郁患者和 54 名健康志愿者。检测外周静脉血中的高敏 CRP、体重指数（BMI）以及抑郁、焦虑和儿童期创伤的问卷评估。估计 CRP 的组间差异，并进行偏最小二乘法（PLS）分析，以探讨 CRP 与特定临床表型的关系。
与健康志愿者相比，治疗抵抗组 BMI 校正后的 CRP 显著升高（P = 0.007；Cohen's d = 0.47）；但治疗缓解组（d = 0.29）和未治疗组（d = 0.18）则不明显。PLS 产生了一个最佳的两因素解决方案，该方案解释了临床测量的 34.7%和 CRP 的 36.0%的变化。与 CRP 相关性最强且在第一 PLS 成分中权重较大的临床表型是植物性抑郁症状、BMI、状态焦虑以及童年时期不被爱或希望有不同的童年。
MDD 患者的 CRP 升高，治疗抵抗患者的 CRP 升高更为明显。与 CRP 升高相关的其他表型包括儿童期逆境和特定的抑郁和焦虑症状。我们认为，根据 CRP 等炎症生物标志物进行分层的 MDD 患者具有独特的临床特征，可能对抗炎药物的二线治疗有反应。利益声明 S.R.C. 为 Cambridge Cognition 和 Shire 咨询；他在该项目中的投入由惠康信托基金会临床研究员资助（110049/Z/15/Z）。E.T.B. 受雇于剑桥大学一半时间，受雇于葛兰素史克一半时间；他持有葛兰素史克的股票。在过去 3 年中，P.J.C. 曾担任 Lundbeck 的顾问委员会成员。N.A.H. 为 GlaxoSmithKline 咨询。P.d.B.、D.N.C.J. 和 W.C.D. 是 Janssen Research & Development，LLC.（Johnson & Johnson 的子公司）的员工，持有 Johnson & Johnson 的股票。其他作者没有报告财务利益或潜在的利益冲突。
