Identifying Reproducible Brain Signatures of Obsessive-Compulsive Profiles

焦虑和相关的疾病，包括强迫症（OCD），是导致 全球残疾的原因。大脑回路异常已经被确定，但重要的是 知识差距依然存在。目前还不清楚哪些异常是什么症状的基础，如何 功能障碍的发展，从而大脑异常的目标与新的干预措施。 此外，电路异常可能跨越传统的诊断类别， 诊断类别，存在个体差异。我们的方法是识别可再生的大脑 可测量的行为和临床症状的特征;这些大脑特征可以被 用于揭示跨诊断疾病的维度，绘制其发展，并开发 直接针对这些电路异常的治疗。 这项提案的目标是识别与以下相关的可重复的大脑签名： 认知和临床特征在强迫症患者中很常见。为了实现这一点， 我们将在五个专家小组中研究250名未用药的强迫症患者和250名健康对照组（HC）。 研究地点横跨五个国家（美国，巴西、印度、荷兰和南非）。 我们将使用最终可用于临床的成像方法， 多个脑回路被认为是强迫症行为的基础，重点是形态测量学（使用T1- 加权MRI）、结构连接（使用扩散张量成像[DTI]）和功能 连接性（使用静息态fMRI [rs-fMRI]）。我们将识别神经成像特征， 通过分析每种模态，用标准化的 协议，并使用多模态融合与现代机器学习统计方法。 然后，我们将研究这些成像特征如何与行为表现联系起来， 认知任务，探测这些相同的电路和一系列的临床概况， 常见的强迫症最后，我们将探讨特定的环境特征（童年） 创伤，社会经济地位，宗教信仰）可能会缓和这种脑行为关系。我们 短期目标是识别强迫症认知和临床特征的大脑特征， 我们的全球合作既招募了一个非常大的未经药物治疗的样本， 签名的再现性。我们的长期目标是识别大脑信号， 行为和临床症状，跨越传统的诊断类别，并使用 这些特征改变了我们如何概念化，诊断和最终治疗精神疾病， 强迫症之类的疾病

Anxiety and related disorders, including obsessive-compulsive disorder (OCD), are leading causes of global disability. Brain circuit abnormalities have been identified, but important knowledge gaps remain. It is unclear which abnormalities underlie what symptom profiles, how dysfunction develops and thus which brain abnormalities to target with new interventions. Moreover, circuit abnormalities likely cut across traditional diagnostic categories and, within a diagnostic category, there is individual variability. Our approach is to identify reproducible brain signatures of measurable behaviors and clinical symptoms; these brain signatures can then be used to reveal trans-diagnostic disease dimensions, to chart their development, and to develop treatments that target these circuit abnormalities directly. The goal of this proposal is to identify reproducible brain signatures associated with cognitive and clinical profiles that are common in individuals with OCD. To accomplish this, we will study 250 unmedicated OCD and 250 healthy control subjects (HCs) at five expert research sites spanning five countries (U.S., Brazil, India, Netherlands, and South Africa). Using imaging methods that could ultimately be adapted for clinical use, we will examine multiple brain circuits thought to underlie OCD behaviors, focusing on morphometry (using T1- weighted MRI), structural connectivity (using Diffusion Tensor Imaging [DTI]), and functional connectivity (using resting-state fMRI [rs-fMRI]). We will identify neuroimaging signatures that distinguish individuals with OCD from HCs by analyzing each modality with standardized protocols and by using multi-modal fusion with modern machine learning statistical methods. We will then examine how these imaging signatures are linked to behavioral performance on cognitive tasks that probe these same circuits and to a range of clinical profiles that are common to OCD. Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, religiosity) may moderate this brain-behavior relationship. Our short-term goal is to identify brain signatures of OCD cognitive and clinical profiles, leveraging our global collaboration both to recruit a very large unmedicated sample and to prove these signatures' reproducibility. Our long-term goal is to identify brain signatures for measurable behaviors and clinical symptoms that cut across traditional diagnostic categories and to use these signatures to transform how we conceptualize, diagnose and ultimately treat mental illnesses like OCD.