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

描述(申请人提供)：老年人的抑郁症并发脑血管疾病和神经变性，这两种疾病都被认为是老年人抗抑郁治疗效果有限的原因之一。然而，老年抑郁症的抑郁综合征和治疗反应的神经生物学基础尚未建立。此R01应用程序的主要目的是描述老年性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性改变，并用此来解释治疗反应的变异性。这项拟议的研究将在老年人中确定与抑郁、接受抑郁治疗和对抑郁治疗做出反应相关的区域大脑活动的变化。为此，我们将使用功能磁共振对80名老年抑郁症患者和40名老年对照组进行调查。受试者将在12周内进行两次功能磁共振扫描。对于抑郁的受试者，扫描将在艾司匹兰开始治疗前和12周后进行。抑郁症的受试者将仅限于65岁及以上的人，他们的第一次抑郁症发作始于60岁或以上。我们将样本限制在这些“晚发性”老年抑郁症受试者，因为根据定义，这些人没有中年抑郁症，因此最有可能表现出晚年特定的生物因素。我们的fMRI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，c)情感反应。这些区域是LLD理论的核心，并与LLD的神经生物学相关的特定脑区有关：外侧前额叶皮质(LPFC)、背侧前扣带回皮质(DACC)、内侧颞叶(MTL)和杏仁核。在特定的任务中，受试者将抑制优先反应(认知控制)，识别以前见过的单词(陈述性记忆)，并对表达情绪的面孔做出反应(情感反应)。功能连通性以及区域活动将使用BOLD功能磁共振信号进行估计。这项研究的结果将描述晚年抑郁症的功能神经解剖学，这将被用来解释为什么一些患者对抗抑郁治疗没有很好的反应。这些治疗反应亚组然后可以作为未来预防和治疗研究的目标。

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.