White matter and emotional and cognitive control in late-onset depression

迟发性抑郁症中的白质与情绪和认知控制

• 批准号: 8343411
• 负责人: Faith M Gunning
• 金额: $ 43.58万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8343411
• 关键词: Address; Affect; Aftercare; Aging; Amygdaloid structure; Anterior; Antidepressive Agents; Area; Behavior; Biological Neural Networks; Brain; Clinical; Cognition; Cognitive; Conflict (Psychology); Data; Depressed mood; Detection; Development; Diffusion Magnetic Resonance Imaging; Dorsal; Dose; Elderly; Emotional; Escitalopram; Family history of; Functional Magnetic Resonance Imaging; Functional disorder; Generations; Geriatric Psychiatry; Goals; Human; Individual; Institutes; Intervention; Lead; Magnetic Resonance Imaging; Measures; Mental Depression; Methods; Modeling; Mood Disorders; Moods; National Institute of Mental Health; Patients; Performance; Phase; Placebos; Predisposition; Prefrontal Cortex; Process; Relative (related person); Risk; Role; Selective Serotonin Reuptake Inhibitor; Source; Stimulus; Structure; Symptoms; System; Testing; Treatment outcome; age related; base; blind; cingulate cortex; clinically relevant; cognitive control; depressive symptoms; early onset; emotion regulation; emotional stimulus; functional disability; geriatric depression; improved; instrument; neural circuit; neuroimaging; neuropsychological; novel; response; translational study; white matter; white matter change

DESCRIPTION (provided by applicant): It has been long held that aging-related brain changes contribute to late onset depression (LOD). We argue that white matter microstructural abnormalities and abnormal activation in the emotional and the cognitive control territories contribute to the development of LOD and to the persistence of its symptoms. To our knowledge, the proposed translational study would be the first to focus on mechanisms of LOD using advanced multimodal neuroimaging methods. Our focus on control networks is based on the following observations: 1) Susceptibility to interference from negatively-valenced irrelevant stimuli (emotional control) may be particularly salient in depression; 2) Difficulty engaging in goal-directed behavior while ignoring irrelevant stimuli (cognitive control) is a cardinal feature f depression and cognitive control processes are preferentially susceptible to advancing age; 3) Poor performance on a traditional neuropsychological measure of cognitive control is associated with persistence of depression despite antidepressant treatment. Consistent with the NIMH RDoC Project mandate to identify "clinically relevant models of circuitry- behavior relationships," the primary aim of this project is to use functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) in individuals with LOD to examine whether dysfunction of the emotional and cognitive control systems are mechanisms by which aging-related brain abnormalities contribute to LOD. For our primary hypotheses we will focus on the role of: 1) Microstructural white matter (WM) abnormalities (measured by probabilistic tractography) and activation of emotional control structures in the development of LOD; and 2) Microstructural WM abnormalities and activation of cognitive control structures in the development of LOD. For our secondary hypotheses, we will focus on the role of microstructural WM abnormalities, activation of control structures and the persistence of LOD despite treatment with an SSRI. The aims will be pursued in 70 patients with LOD and 70 non-depressed older adults. The LOD group will undergo a 2-week, single-blind, placebo lead-in, psychotropic washout phase at the end of which they will complete an MRI session that includes fMRI and DTI. Patients will then receive 12 weeks of escitalopram treatment at the target daily dose of 20 mg. In addition to testing our hypotheses, the study enables exploratory analyses of: 1) The relationships among WM hyperintensities, control system activations, and the development and persistence of LOD; and 2) Relationships of control network activation post-treatment to a. baseline activation and WM integrity and b. persistence of depression at 12 weeks. We expect this MRI study of LOD to offer novel information about the neural circuitry mechanisms of depression. In addition, the identification of structural and functional impairments of LOD can aid the development of clinical instruments and targeted interventions. PUBLIC HEALTH RELEVANCE: This MRI study has the potential to identify how abnormalities in brain systems that control the ability to ignore irrelevant information may contribute to the development of depression in older adults. We hope that its findings may promote the development of tests that may improve the detection of patients at risk for poor treatment outcomes and eventually guide the development of novel treatments for depression.

描述（由申请人提供）：长期以来，与衰老相关的大脑变化有助于晚期发作抑郁症（LOD）。我们认为，情绪和认知控制领域的白质微结构异常和异常激活有助于LOD的发展以及其症状的持久性。据我们所知，拟议的翻译研究将是第一个使用先进的多模式神经影像学方法专注于LOD机制的研究。我们对控制网络的关注是基于以下观察结果：1）对受负相关的无关刺激（情绪控制）干扰的敏感性可能在抑郁症中特别重要； 2）在忽略无关紧要的刺激（认知控制）的同时，难以从事目标指导行为，这是基本特征F抑郁症，认知控制过程优先易受增长年龄的影响； 3）尽管抗抑郁药治疗，对传统的认知控制神经心理学测量的表现不佳与抑郁症的持续性有关。与NIMH RDOC项目授权一致，以确定“电路行为关系的临床相关模型”， 该项目的主要目的是使用LOD个体中的功能磁共振成像（fMRI）和扩散张量成像（DTI）来检查情绪和认知控制系统的功能障碍是否是衰老相关脑异常的机制。对于我们的主要假设，我们将重点介绍：1）微结构白质（WM）异常（通过概率拖拉术衡量）以及情绪控制结构在LOD发展中的激活； 2）微结构的WM异常和LOD发展中认知控制结构的激活。对于我们的次要假设，我们将重点关注微结构WM异常的作用，控制结构的激活以及尽管用SSRI进行治疗，LOD的持久性。在70名LOD和70名未抑郁的老年人的患者中，将追求目标。 LOD组将在结尾处进行2周的单盲，安慰剂铅，精神冲洗阶段，他们将完成包括fMRI和DTI在内的MRI会议。然后，患者将在目标每日剂量为20 mg时接受12周的依此所治疗。除了检验我们的假设外，该研究还提供了：1）WM高强度，控制系统激活以及LOD的发展和持久性之间的关系； 2）控制网络激活后处理与a的关系。基线激活和WM完整性和b。抑郁症的持久性在12周。我们希望对LOD的MRI研究提供有关抑郁症神经回路机制的新信息。另外，鉴定LOD的结构和功能障碍可以帮助开发临床工具和有针对性的干预措施。 公共卫生相关性：这项MRI研究有可能确定脑系统中的异常如何控制忽略无关信息的能力，可能会导致老年人抑郁症的发展。我们希望它的发现可以促进测试的发展，从而可以改善对治疗结果不良风险的患者的检测，并最终指导开发抑郁症的新型治疗方法。