Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort
Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort
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DOI：
10.1186/s12888-016-0785-x
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发表时间：
2016-04-16
期刊：
影响因子：
4.4
通讯作者：
Kennedy, Sidney H.
中科院分区：
文献类型：
--
作者：
Lam, Raymond W.;Milev, Roumen;Kennedy, Sidney H.
背景：重度抑郁症（MDD）是世界范围内最普遍和致残的疾病之一。识别治疗反应的临床和生物标志物（“生物标志物”）可以个性化临床决策并导致更好的结果。本文描述了一项由加拿大抑郁症生物标志物整合网络（CAN-BIND）进行的抗抑郁治疗反应生物标志物发现研究的目的、设计和方法。CAN-BIND研究项目调查并确定有助于预测抗抑郁药物治疗的重度抑郁症患者预后的生物标志物。这项初步研究（被称为CAN-BIND-1）的主要目的是确定个体和综合神经影像学、电生理、分子和临床预测因素对顺序抗抑郁药单药治疗和辅助治疗的反应。方法：CAN-BIND-1是一个多站点倡议，涉及6个学术卫生中心与其他大学和研究中心合作。在为期16周的方案中，重度抑郁症患者接受一线抗抑郁药（艾司西酞普兰10- 20mg /d）治疗，如果8周后临床证明有必要，则增加基于证据的附加药物（阿立哌唑2- 10mg /d）。使用临床评定量表获得综合数据集；行为、维度和功能/生活质量措施；神经认知测试;血液样本的基因组、遗传和蛋白质组分析；结构与功能磁共振联合成像；和脑电图。来自所有站点的去识别数据聚合在一个安全的神经信息学平台中，用于数据集成、管理、存储和分析。统计分析将包括多变量和机器学习技术，以确定治疗反应的预测因素、调节因素和中介因素。讨论：从2013年6月至2015年2月，对134名参与者（85名重度抑郁症门诊患者和49名健康参与者）的基线进行了评估。该队列的临床特征与其他重度抑郁症研究相似。所有站点的招募工作正在进行，目标样本为290名参与者。CAN-BIND将通过广泛的临床、分子和影像学评估来识别MDD治疗反应的生物标志物，以改善治疗实践和临床结果。它还将为未来的研究创造一个创新的、强大的平台和数据库。
Background: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD.Methods: CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response.Discussion: From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.