Columbia University Irving Medical Center, Columbia University, New York, NY, 10032, USA.
The New York State Psychiatric Institute, New York, NY, 10032, USA.
BMC Psychiatry. 2020 Feb 14;20(1):68. doi: 10.1186/s12888-020-2439-2.
Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2-3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results.
We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations.
Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it.
强迫症（OCD）的终身患病率为 2-3%，是全球残疾的主要原因。已经确定了 OCD 患者大脑回路异常，但仍存在重要的知识空白。本文描述的新全球倡议的目标是确定可衡量行为和常见 OCD 患者临床症状的稳健且可重复的大脑特征。选择全球方法是为了加速发现，提高严谨性和透明度，并确保结果的普遍性。
我们将在五个国家（巴西、印度、荷兰、南非和美国）的五个专家研究地点研究 250 名未服用药物的 OCD 成年患者、100 名未受影响的 OCD 患者成年兄弟姐妹和 250 名健康对照者。所有参与者将接受临床评估、神经认知评估和磁共振成像（MRI）。影像学将检查多个假设为 OCD 行为提供基础的大脑回路，重点是形态计量学（T1 加权 MRI）、结构连接（弥散张量成像）和功能连接（静息状态 fMRI）。除了分别分析每种成像方式外，我们还将使用多模态融合与机器学习统计方法，试图从 MRI 中提取出能够区分 OCD 患者与未受影响的兄弟姐妹和健康对照者的成像特征（目标 #1）。然后，我们将检查这些成像特征如何与神经认知任务的行为表现相关联，这些任务也会探测到相同的大脑回路，以及与临床特征相关联（目标 #2）。最后，我们将探索特定的环境特征（儿童时期的创伤、社会经济地位和宗教信仰）如何调节这些大脑-行为关联。
使用数据收集和分析的协调方法，我们将进行迄今为止最大的、针对未服用药物的 OCD 患者的神经认知和多模态成像研究。通过招募一个大型的、具有种族文化多样性的样本，我们将检验是否存在跨越国家和文化的 OCD 核心特征的稳健生物标志物。如果是这样，未来的研究可以使用这些大脑特征来揭示跨诊断疾病维度，描绘这些特征在何时出现于发育过程中，并确定直接针对这些大脑回路异常的治疗方法。这项研究的长期目标不仅是改变我们对 OCD 的概念化方式，还包括改变我们的诊断和治疗方式。
