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）：涉及抑郁症和焦虑的内部化精神病理学（IP）是最普遍，昂贵和残疾的疾病。可以使用IP的治疗方法，但是个别患者反应的程度是相当异质的。很少有信息，特别是在生物领域中，这有助于解释治疗反应中的个体差异。 NIMH的研究领域标准（RDOC）项目可以通过鼓励超出某些分类疾病及其相关症状的创新研究来解决这一问题，从而朝着更广泛的，CORE（RDOC）构造与脑病理生理学有关，并跨疾病共享。 IP在额额 - 束缚影响调节和情感显着性（Flares）脑电路中具有相似的功能障碍模式，以及两种常用的“黄金标准”治疗方法 - 选择性5-羟色胺再摄取抑制剂（SSRIS）（SSRIS）和认知行为疗法和认知行为疗法（CBTS） - 在焦虑和压抑的范围内同样有效，并且在焦虑症中都具有相同的范围，并且在大脑中都具有相同的变化。拟议项目的总体目标是描述SSRI和CBT的常见大脑靶标与特定的耀斑大脑目标，并确定耀斑功能障碍的特定方面，可以更好地预测对两者的反应以及对特定治疗方式的反应。提出的实验将情感及其与认知的相互作用融合在一起，在情感体验的几个阶段，包括对急性和潜在威胁的敏感性以及与耀斑脑网络相关的影响调节的敏感性的研究。这些实验将生成有关多层分析层的负价系统（NVS）RDOC结构域的数据（fMRI和EEG的神经回路，皮肤电导和惊吓反应，用于生理，性能和行为的自我报告）。我们建议将200名患者招募参加我们的情绪和焦虑症计划，以寻求治疗“焦虑，忧虑，情绪低落”（IP，包括未指定的特征的人），并将其随机化为12周的SSRI或CBT课程。每次处理之前和之后，将测量尺寸，转诊NVS构建体，包括耀斑功能。具体而言，该项目将研究2个特定目的：1）SSRI和CBT处理如何在哪里以及如何对NVS构建体发挥作用？ 2）哪些NV构建体可以预测SSRI和CBT处理成功的可能性？这样的发现可用于指导合适的患者获得成功可能性最高的正确治疗方法。他们还阐明了以病理生理驱动的机械模型的何处以及如何在大脑中起作用，从而加快了针对基本病理生理学跨内在疾病的新疗法的发展。