Supplementary Material for: An increase in C-reactive protein levels during antidepressant treatment as a candidate marker for treatment non-response in major depressive disorder

Introduction
One-third of patients with major depressive disorder (MDD) exhibit low-grade inflammation as reflected by C-reactive protein (CRP) concentrations > 3 mg/L. We explored whether CRP changes from baseline to week one of antidepressant treatment (ΔCRP) can serve as a marker of treatment response.
Methods
CRP serum levels were measured at baseline and after the first week of treatment in 33 MDD patients and correlated with patients’ Hamilton depression scale (HAM-D), while adjusting for age, gender and body mass index. We assessed antidepressant responses at weeks one and four of treatment as a > 25% and > 50% HAM-D score reduction (ΔHAM-D) compared to baseline, respectively. We compared baseline and week-one CRP levels with the paired t-test within responders and non-responders separately and ΔCRP between the groups with the ANCOVA.
Results
Higher ΔCRP correlated with lower week-four ΔHAM-D scores (r = -0.5, p = 0.006). Non-responders showed higher ΔCRP – but not baseline and week-one CRP – than responders (p = 0.018, Cohen’s d = 1.1). A ΔCRP increase was observed in 13/16 (81%) non-responders and 7/17 (41%) responders (Fisher’s exact test’s p = 0.03). A ΔCRP increase combined with a week-one non-response was observed in 13/16 (81%) non-responders and 1/17 (6%) responders (p < 0.0001).
Conclusions
Rather ΔCRP at week one than baseline CRP might be indicative of treatment response at week four, especially if combined with week-one ΔHAM-D. In the future, ΔCRP could be introduced into psychiatric practice to guide treatment plans.

引言
约三分之一的重度抑郁症（Major Depressive Disorder, MDD）患者存在低度炎症状态，表现为C反应蛋白（C-reactive Protein, CRP）浓度＞3mg/L。本研究旨在探讨抗抑郁治疗基线至第1周的CRP变化量（ΔCRP）是否可作为治疗应答的标志物。

方法
本研究对33名MDD患者分别于治疗基线及第1周后检测血清CRP水平，并校正年龄、性别与体质量指数后，将其与患者的汉密尔顿抑郁量表（Hamilton Depression Scale, HAM-D）评分进行相关性分析。分别以较基线HAM-D评分降低＞25%、＞50%作为治疗第1周及第4周的抗抑郁应答判定标准，计算HAM-D评分变化量（ΔHAM-D）。分别在应答者与无应答者组内采用配对t检验比较基线与第1周CRP水平，采用协方差分析（Analysis of Covariance, ANCOVA）比较两组间的ΔCRP。

结果
ΔCRP升高与第4周ΔHAM-D评分降低程度呈负相关（r=-0.5，p=0.006）。无应答者的ΔCRP水平显著高于应答者（基线及治疗第1周CRP水平则无此组间差异，p=0.018，Cohen’s d=1.1）。13/16（81%）的无应答者出现ΔCRP升高，而应答者中该比例为7/17（41%）（Fisher确切概率法检验p=0.03）。同时出现ΔCRP升高与第1周无应答的比例在无应答者中为13/16（81%），应答者中仅为1/17（6%）（p＜0.0001）。

结论
相较于基线CRP水平，第1周的ΔCRP更能预测第4周的治疗应答情况，尤其是联合第1周ΔHAM-D评分时。未来ΔCRP可应用于精神科临床实践，以辅助制定治疗方案。