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: 9068241
• 负责人: Faith M Gunning
• 金额: $ 32.66万
• 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 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9068241
• 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; Research Domain Criteria; Risk; Role; Selective Serotonin Reuptake Inhibitor; Single-Blind Study; Source; Stimulus; Structure; Symptoms; System; Testing; Treatment outcome; White Matter Hyperintensity; age related; base; brain abnormalities; cingulate cortex; clinically relevant; cognitive control; depressed patient; 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.

描述（由申请人提供）：长期以来，人们一直认为与衰老相关的大脑变化会导致迟发性抑郁症（LOD）。我们认为，白质微观结构异常以及情绪和认知控制区域的异常激活导致 LOD 的发展及其症状的持续存在。据我们所知，拟议的转化研究将是第一个使用先进的多模态神经影像方法关注 LOD 机制的转化研究。我们对控制网络的关注基于以下观察：1）对负价不相关刺激（情绪控制）的干扰的敏感性在抑郁症中可能特别突出； 2）难以进行目标导向的行为，同时忽略不相关的刺激（认知控制）是抑郁症的一个主要特征，并且认知控制过程更容易受到年龄增长的影响； 3）传统的认知控制神经心理学测量表现不佳与尽管接受抗抑郁治疗但抑郁症持续存在相关。与 NIMH RDoC 项目的任务一致，即确定“电路行为关系的临床相关模型”， 该项目的主要目的是在患有LOD的个体中使用功能磁共振成像（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与衰老相关的大脑异常导致LOD的机制。对于我们的主要假设，我们将重点关注以下作用：1）微结构白质（WM）异常（通过概率纤维束描记术测量）和情绪控制结构的激活在 LOD 的发展中； 2) LOD 发展过程中的微观结构 WM 异常和认知控制结构的激活。对于我们的次要假设，我们将重点关注微观结构 WM 异常的作用、控制结构的激活以及尽管使用 SSRI 治疗但 LOD 的持续存在。该目标将在 70 名 LOD 患者和 70 名非抑郁老年人中实现。 LOD 组将经历为期 2 周的单盲、安慰剂导入、精神药物清除阶段，最后他们将完成包括 fMRI 和 DTI 在内的 MRI 会议。然后，患者将接受为期 12 周的艾司西酞普兰治疗，每日目标剂量为 20 毫克。除了测试我们的假设之外，该研究还可以对以下内容进行探索性分析：1）WM 高信号、控制系统激活以及 LOD 的发展和持续性之间的关系； 2) 控制网络激活后处理与a的关系。基线激活和 WM 完整性 b．抑郁症持续 12 周。我们期望这项 LOD 的 MRI 研究能够提供有关抑郁症神经回路机制的新信息。此外，识别 LOD 的结构和功能损伤可以帮助开发临床仪器和有针对性的干预措施。