Behavioral and Neural Heterogeneity in OCD and Depression

强迫症和抑郁症的行为和神经异质性

• 批准号: 10672403
• 负责人: Emily R Stern
• 金额: $ 70.08万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-05 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10672403
• 关键词: Address; Anterior; Behavior; Behavioral; Brain; Characteristics; Clinical; Communities; Complement; Data; Data Analyses; Depressed mood; Development; Diagnosis; Diagnostic; Dimensions; Disease; Etiology; Functional Magnetic Resonance Imaging; Future; Goals; Heterogeneity; Human; Individual; Insula of Reil; Interoception; Intervention; Investigation; Link; Machine Learning; Major Depressive Disorder; Measures; Mediating; Mental Depression; Mental disorders; Modeling; Neurobiology; Obsessive compulsive behavior; Obsessive-Compulsive Disorder; Patients; Pattern; Phenotype; Prediction of Response to Therapy; Prefrontal Cortex; Prevalence; Protocols documentation; Research; Research Domain Criteria; Rest; Sampling; Severities; Source; Subgroup; Symptoms; Thinking; Work; behavior measurement; biotypes; bodily sensation; brain circuitry; cingulate cortex; clinical heterogeneity; comorbidity; connectome; data acquisition; depressive symptoms; disability; effective therapy; individual patient; inventory of depressive symptomatology; neural; neurobehavioral; neurobiological mechanism; neuroimaging; novel; personalized intervention; personalized medicine; psychologic; recruit; symptom cluster; unsupervised learning

Project Summary This project investigates behavioral and neural heterogeneity in obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) using hypothesis- and data-driven approaches. OCD and MDD are major sources of disability worldwide, with fewer than half of patients responding adequately to first-line treatments. Treatment may be impeded by the fact that OCD and MDD are both highly heterogeneous, with clusters of symptoms likely derived from differing psychological and neurobiological etiologies. The Research Domain Criteria (RDoC) framework seeks to address this problem in part by investigating dimensional components of behavior that span across disorders and more closely align with brain circuitry than does the multifaceted diagnostic phenotype. In the present project, we follow an RDoC approach to the study of heterogeneity by investigating relationships between behavior, clinical symptoms, and brain function using task-based and resting-state fMRI in a sample of 75 OCD patients and 75 MDD patients. Our preliminary data in OCD patients and individuals with depressive symptoms point to interoceptive sensitivity (IS) and perseverative negative thinking (PT) as dimensional components of behavior that are not only transdiagnostic but also explain important within-disorder heterogeneity; the first aim of this proposal builds on these findings by investigating associations of IS and PT with clinical symptoms, behavior, and brain function in OCD and MDD. Complementing this hypothesis-driven approach, the second aim of the project is a data-driven investigation using unsupervised machine learning (ML) to uncover neurobiological profiles that characterize variability in brain function across OCD and MDD. Building on our preliminary analysis identifying three subgroups within OCD distinguished by differential patterns of resting-state functional connectivity, we will investigate neurobiological heterogeneity across OCD and MDD and link clinical and behavioral data to neurobiological subgroups using a comprehensive ‘deep phenotyping’ approach to data acquisition and analysis. The overarching goals of both aims are to identify factors contributing to heterogeneity that can be developed as novel targets for personalized treatments based on an individual patient’s neurobehavioral profile.

项目摘要 该项目调查了强迫症（OCD）和主要的行为和神经异质性 使用假设和数据驱动方法的抑郁症（MDD）。强迫症和MDD是主要来源 全球残疾人，只有不到一半的患者对一线治疗做出适当反应。治疗 强迫症和MDD都是高度异质的，可能会阻碍 源自区分心理和神经生物学病因。研究领域标准（RDOC） 框架旨在通过研究跨越行为的维数组成部分来解决此问题 跨疾病和与脑电路更紧密相比，比多方面的诊断表型。 本项目，我们通过研究关系遵循RDOC方法来研究异质性 在行为，临床症状和大脑功能之间，使用基于任务的静止状态fMRI在一个样本中 75例强迫症患者和75例MDD患者。我们在强迫症患者和抑郁症患者中的初步数据 症状指向互感敏感性（IS）和持续的负面思维（PT） 行为的组成部分不仅是经诊断的，而且还解释了重要的内部。 异质性；该提案的第一个目的是通过调查IS和PT的关联来建立这些发现的基础 OCD和MDD中的临床症状，行为和大脑功能。补充这一假设驱动的 方法，该项目的第二个目的是使用无监督的机器学习（ML）进行数据驱动的调查 揭示表征OCD和MDD脑功能变异性的神经生物学特征。建筑 在我们的初步分析中，确定OCD中的三个亚组，以差异模式区分 静止状态的功能连通性，我们将研究OCD和MDD的神经生物学异质性 使用全面的“深度表型”将临床和行为数据与神经生物学亚组联系起来 数据获取和分析的方法。这两个目标的总体目标是确定促成的因素 对于基于个人的个性化治疗的新颖目标，可以发展为异质性 患者的神经行为轮廓。