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: 8517821
• 负责人: Faith M Gunning
• 金额: $ 36.5万
• 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/8517821
• 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.

描述（申请人提供）：长期以来，人们一直认为与年龄相关的大脑变化会导致晚发性抑郁症（LOD）。我们认为，情绪和认知控制区域的白质微结构异常和异常激活有助于LOD的发展及其症状的持续。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成像方法关注LOD机制的研究。我们对控制网络的关注是基于以下观察：1)对负效无关刺激（情绪控制）干扰的易感性在抑郁症中可能特别突出；(2)在忽视无关刺激的情况下难以进行目标导向行为（认知控制）是抑郁症的主要特征，认知控制过程优先受年龄的影响；3)传统的认知控制神经心理学测试表现不佳与抑郁症的持续存在有关，尽管进行了抗抑郁治疗。根据NIMH RDoC项目的授权，确定“临床相关的电路-行为关系模型”，