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

描述（由申请人提供）：老年抑郁症并发脑血管疾病和神经退行性变，这两种疾病被认为是导致老年人抗抑郁治疗疗效有限的原因。然而，抑郁综合征的神经生物学基础和老年抑郁症的治疗反应尚未建立。该R 01应用的主要目的是表征老年重性抑郁症的功能神经解剖学，我们认为其特征在于功能连接的改变，并以此来解释治疗反应的变异性。这项拟议的研究将确定老年人与抑郁症相关的区域大脑活动的变化，治疗抑郁症，以及对抑郁症治疗的反应。为此，我们将调查，与功能磁共振成像，80名老年抑郁症患者和40名老年对照。受试者将接受两次fMRI扫描，间隔12周。对于抑郁症受试者，扫描将在艾司西酞普兰治疗开始前和开始后12周进行。抑郁症受试者将限于65岁及以上的个体，其首次抑郁症发作始于60岁或以上。我们将我们的样本限制在这些“晚发性”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，因此最有可能表现出晚年特定的生物学因素。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）陈述性记忆和c）情感反应。这些是LLD理论的核心，并且与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。在特定的任务中，受试者会抑制优势反应（认知控制），识别以前看到的单词（陈述性记忆），并对表达情感的面孔做出反应（情感反应）。功能连接，以及区域活动，将估计使用BOLD功能磁共振成像信号。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，这将被用来解释为什么有些患者对抗抑郁症治疗反应不佳。这些治疗反应亚组可以作为未来预防和治疗研究的目标。

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.