Altered Functioning of Cognitive and Affective Circuits in Late-Life Depression

晚年抑郁症中认知和情感回路功能的改变

• 批准号: 7383129
• 负责人: HOWARD J AIZENSTEIN
• 金额: $ 31.96万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7383129
• 关键词: Affective; Age; Aging; Alzheimer' s Disease; Amygdaloid structure; Anterior; Antidepressive Agents; Belief; Biological; Biological Factors; Brain; Brain region; Cerebrovascular Disorders; Cognition; Cognitive; Data; Depressed mood; Depressive Syndromes; Diagnosis; Diffusion Magnetic Resonance Imaging; Disease; Distress; Dorsal; Elderly; Escitalopram; Expressed Emotion; Face; Functional Magnetic Resonance Imaging; Future; Goals; Grant; Health Services Research; Heart Diseases; Heterogeneity; Hippocampus (Brain); Impaired cognition; Individual; Intervention; Intervention Studies; Joints; K-Series Research Career Programs; Lateral; Lead; Link; MRI Scans; Measures; Medial; Mediating; Medical; Memory; Mental Depression; Methods; Modeling; Mood Disorders; Nerve Degeneration; Neural Pathways; Neuroanatomy; Neurobiology; Numbers; Outcome; Pathway interactions; Patients; Pharmacotherapy; Pilot Projects; Prefrontal Cortex; Prevention; Process; Public Health; Rate; Research; Research Infrastructure; Research Personnel; Resistance; Sampling; Scanning; Signal Transduction; Structure; Subgroup; Suicide; Temporal Lobe; Testing; Time; Week; adjudicate; aged; base; burden of illness; cerebrovascular; cingulate cortex; cognitive change; cognitive control; cognitive function; demographics; depressive symptoms; design; disability; executive function; geriatric depression; geriatric major depression; improved; interest; memory encoding; middle age; neural circuit; neuropsychological; relating to nervous system; research study; response; theories; white matter

DESCRIPTION (provided by applicant): Depression in the elderly is complicated by both cerebrovascular disease and neurodegeneration, both of which are believed to contribute to the limited efficacy of antidepressant treatment in the elderly. However, the neurobiologic basis of the depressive syndrome and treatment response in late-life depression have not been established. The primary aim of this R01 application is to characterize the functional neuroanatomy of geriatric major depression, which we believe is characterized by altered functional connectivity, and use this to explain treatment response variability. The proposed study will identify in elderly individuals the changes in regional brain activity associated with being depressed, being treated for depression, and responding to depression treatment. To this end we will investigate, with fMRI, eighty elderly depressed subjects and 40 elderly controls. Subjects will undergo fMRI scanning on two occasions 12 weeks apart. For the depressed subjects, the scanning will occur just before and 12 weeks after initiating treatment with escitalopram. The depressed subjects will be restricted to individuals aged 65 and older, whose first episode of depression started at age 60 or older. We limit our sample to these 'late-onset' elderly depression subjects because, by definition, these individuals did not have mid-life depression, and thus should be most likely to show late-life specific biological factors. Our fMRI tasks target three of the key cognitive and affective neural pathways associated with LLD: a) cognitive control, b) declarative memory, and c) affective reactivity. These are central to theories of LLD and are associated with specific brain regions that have been linked to the neurobiology of LLD: the lateral prefrontal cortex (LPFC), the dorsal anterior cingulate cortex (dACC); the medial temporal lobe (MTL), and the amygdala. In the specific tasks, subjects will inhibit a prepotent response (cognitive control), recognize previously seen words (declarative memory), and respond to faces expressing emotion (affective reactivity). Functional connectivity, as well regional activity, will be estimated using the BOLD fMRI signal. The results of this study will characterize the functional neuroanatomy of late- life depression, which will be used to explain why some patients do not respond well to anti-depressant treatment. These treatment response subgroups can then serve as targets for future prevention and treatment studies.

描述（由申请人提供）：老年人的抑郁症因脑血管疾病和神经变性而复杂化，这两种疾病被认为是导致老年人抗抑郁治疗效果有限的原因。然而，抑郁综合征的神经生物学基础和晚年抑郁症的治疗反应尚未确定。该 R01 应用的主要目的是表征老年重度抑郁症的功能神经解剖学特征，我们认为其特征是功能连接改变，并用它来解释治疗反应的变异性。拟议的研究将确定老年人中与抑郁、接受抑郁治疗以及对抑郁治疗的反应相关的区域大脑活动的变化。为此，我们将利用功能磁共振成像技术对 80 名老年抑郁症受试者和 40 名老年对照者进行调查。受试者将接受两次功能磁共振成像扫描，间隔 12 周。对于抑郁症受试者，扫描将在开始艾司西酞普兰治疗之前和之后 12 周进行。抑郁症受试者将仅限于 65 岁及以上的个体，其首次抑郁症发作于 60 岁或以上。我们将样本限制在这些“晚发”老年抑郁症受试者中，因为根据定义，这些人没有中年抑郁症，因此应该最有可能表现出晚年特定的生物因素。我们的功能磁共振成像任务针对与 LLD 相关的三个关键认知和情感神经通路：a) 认知控制，b) 陈述性记忆，以及 c) 情感反应。这些是 LLD 理论的核心，并且与与 LLD 的神经生物学相关的特定大脑区域相关：外侧前额叶皮层 (LPFC)、背侧前扣带皮层 (dACC)；内侧颞叶 (MTL) 和杏仁核。在特定任务中，受试者将抑制优势反应（认知控制），识别以前见过的单词（陈述性记忆），并对表达情感的面孔做出反应（情感反应）。将使用 BOLD fMRI 信号来估计功能连接以及区域活动。这项研究的结果将描述晚年抑郁症的功能神经解剖学特征，这将用于解释为什么一些患者对抗抑郁治疗反应不佳。这些治疗反应亚组可以作为未来预防和治疗研究的目标。