Negative Valence Brain Targets and Predictors of Anxiety and Depression Treatment

负价大脑目标和焦虑和抑郁治疗的预测因子

• 批准号: 8573679
• 负责人: K. Luan Phan
• 金额: $ 62.51万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-23 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8573679
• 关键词: Acute; Affect; Anxiety; Anxiety Disorders; Area; Behavior; Behavioral; Biological; Brain; Clinical; Cognition; Cognitive; Cognitive Therapy; Data; Depressed mood; Depressive disorder; Development; Diagnosis; Diagnostic; Dimensions; Disease; Electroencephalography; Emotional; Emotions; Enrollment; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Galvanic Skin Response; Genes; Goals; Gold; Individual; Individual Differences; Judgment; Link; Literature; Measures; Mental Depression; Mental disorders; Modality; Modeling; Mood Disorders; Patient Preferences; Patient Rights; Patients; Pattern; Performance; Pharmaceutical Preparations; Physiology; Problem Solving; Process; Psychopathology; Psychotherapy; Publishing; Randomized; Regulation; Research; Right to Treatments; Science; Selective Serotonin Reuptake Inhibitor; Specific qualifier value; Staging; Symptoms; System; Treatment outcome; Work; base; brain behavior; design; emotional experience; healthy volunteer; innovation; neural circuit; programs; public health relevance; research study; response; self reported behavior; standard care; success; systems research; treatment response

DESCRIPTION (provided by applicant): Internalizing psychopathologies (IPs) involving depression and anxiety are among the most prevalent, costly and disabling illnesses. Treatments for IPs are available but the extent to which individual patients respond is quite heterogeneous. Little information exists, particularly in the biological domain, which helps to explain individual differences in treatment response. The NIMH's Research Domain Criteria (RDoC) project may solve this problem by encouraging innovative research beyond certain categorical disorders and their associated symptoms, towards broader, core (RDoC) constructs related to brain pathophysiology, and that are shared across disorders. IPs share similar patterns of dysfunction within the Fronto-Limbic Affect Regulation and Emotional Salience (FLARES) brain circuit, and two commonly used, 'gold standard' treatments - selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapies (CBTs) - are equally effective for both anxiety and depressive disorders, and appear to change brain activity in the same areas within the FLARES circuit. The overarching goal of the proposed project is delineate what are common versus specific FLARE brain targets for SSRI and CBT and identify specific aspects of FLARE dysfunction that might better predict response to both and to a specific modality of treatment. The proposed experiments integrate emotion and its interaction with cognition across several stages of emotional experience, encompassing studies that probe sensitivity to acute and potential threat and automatic and volitional forms of affect regulation in relation to the FLARES brain network. These experiments will generate data on the negative valence systems (NVS) RDoC domain for multiple layers of analysis (fMRI and EEG for neural circuits, skin conductance and startle response for physiology, performance and self-reports for behavior). We propose to enroll 200 patients presenting to our Mood and Anxiety Disorders Program seeking treatment for disabling 'anxiety, worry, depressed mood' (IP,s including those characterized as Not Otherwise Specified) and randomize them to a 12-week course of SSRI or CBT. Dimensional, transdiagnostic NVS constructs, including FLARES function, will be measured before and after each treatment. Specifically, the project will examine 2 Specific Aims: 1) Where and how do SSRI and CBT treatments exert their effects on NVS constructs?; and 2) Which NVS construct can predict the likelihood of success from SSRI and CBT treatment? Such findings can be used to guide the right patients to the right treatments with the highest likelihood of success. They also elucidate a pathophysiologically-driven mechanistic model of where and how treatments work in the brain and thus hasten the development of new treatments that target the underlying pathophysiology across internalizing conditions.

描述（由申请人提供）：涉及抑郁和焦虑的内化精神病理学（IP）是最普遍、最昂贵和致残的疾病之一。 IP 的治疗方法是可用的，但个体患者的反应程度却相当不同。现有的信息很少，特别是在生物领域，这有助于解释治疗反应的个体差异。 NIMH 的研究领域标准 (RDoC) 项目可以通过鼓励超越某些分类疾病及其相关症状的创新研究，转向与脑病理生理学相关且跨疾病共享的更广泛的核心 (RDoC) 结构来解决这个问题。 IP 在额叶边缘情感调节和情绪凸显 (FLARES) 大脑回路中具有相似的功能障碍模式，并且两种常用的“黄金标准”治疗方法 - 选择性血清素再摄取抑制剂 (SSRI) 和认知行为疗法 (CBT) - 对于焦虑症和抑郁症同样有效，并且似乎会改变 FLARES 回路内相同区域的大脑活动。该项目的总体目标是描述 SSRI 和 CBT 的常见 FLARE 脑靶点与特定 FLARE 脑靶点，并确定 FLARE 功能障碍的特定方面，从而可以更好地预测对两者和特定治疗方式的反应。拟议的实验将情绪及其与认知的相互作用整合到情绪体验的多个阶段，包括探索对急性和潜在威胁的敏感性以及与 FLARES 大脑网络相关的自动和意志形式的情感调节的研究。这些实验将生成负价系统 (NVS) RDoC 域的数据，用于多层分析（用于神经回路的功能磁共振成像和脑电图、用于生理学的皮肤电导和惊吓反应、用于行为的表现和自我报告）。我们建议招募 200 名患者参加我们的情绪和焦虑障碍项目，寻求治疗以消除“焦虑、担忧、抑郁情绪”（IP，包括那些未另行指定的特征），并将他们随机分配到为期 12 周的 SSRI 或 CBT 疗程中。每次治疗之前和之后都会测量维度、跨诊断 NVS 结构，包括 FLARES 功能。具体来说，该项目将研究 2 个具体目标：1）SSRI 和 CBT 治疗在何处以及如何对 NVS 结构发挥作用？ 2) 哪种 NVS 结构可以预测 SSRI 和 CBT 治疗成功的可能性？这些发现可用于指导正确的患者接受正确的治疗，成功的可能性最高。他们还阐明了病理生理学驱动的机制模型，说明治疗在大脑中的位置和方式，从而加速针对跨内化条件的潜在病理生理学的新疗法的开发。