Vascular Depression: Longitudinal Followup

描述(由申请人提供)：一项重要的研究支持血管疾病在老年抑郁症发病机制中的作用。已有研究表明，血管疾病影响参与情绪调节的白质通路和皮质下结构，并与认知功能和治疗抵抗力下降有关。虽然已经描述了一些横断面观察，但这些异常如何预测纵向过程尚不清楚。此外，白质病理与重要灰质结构的结构变化之间的相互作用还没有得到充分的研究，这些结构包括眼眶额叶皮质、杏仁核、海马体和基底节。这项拟议的研究将对NIH资助的“血管性抑郁症的治疗结果”研究招募的老年抑郁症(LLD)受试者进行明确的队列研究。在这项研究中，我们发现基线认知和结构性措施与抗抑郁药物的急性反应之间存在关联。在目前的提案中，我们将扩展这些发现，以确定它们对抑郁症纵向病程的影响。这项拟议的研究将检验基线神经成像结果和认知功能在预测五年随访病程方面的效果。我们建议对之前在杜克大学和华盛顿大学进行的“血管性抑郁症的治疗结果”研究的168名老年受试者进行合作研究。他们将接受随访的磁共振成像、神经心理测试和仔细的间歇史，重点关注他们的抑郁史、抗抑郁药物的使用和病史，以检验以下假设：1)纵向病程5年内有更多抑郁发作的LLD个体在a)白质结构指标上将有更大的基线损害；b)杏仁核、海马体和眶前皮质体积较小；3)神经心理功能；2)LLD个体在纵向病程5年内有更多抑郁发作的个体在过渡期间这些MRI和神经心理测试变量将有更大的变化。在次级目标中，我们将检验这些措施的交互作用对抑郁持续时间的影响，并检验特定纤维束的连通性对抑郁病程的影响。该提案将为导致老年人复发或慢性抑郁症的神经放射学和神经心理学因素提供重要的新数据。

DESCRIPTION (provided by applicant): A significant body of research supports a role of vascular disease in the pathogenesis of late-life depression. It has been proposed that vascular disease affects white matter pathways and subcortical structures involved in mood regulation and is associated with poorer cognitive function and treatment resistance. While a number of cross-sectional observations have been described, it is not known how these abnormalities predict longitudinal course. Further, the interaction between white matter pathology and structural changes in important gray matter structures, including orbitofrontal cortex, amygdala, hippocampus and basal ganglia is not fully studied. The proposed study will follow up a well defined cohort of late life depressed (LLD) subjects recruited for the NIH-funded "Treatment Outcome of Vascular Depression" study. In that study we have found an association between baseline cognitive and structural measures and acute response to antidepressants. In the current proposal we will extend those findings to determine their impact on longitudinal course of depression. The proposed study will examine the effect of baseline neuroimaging findings and cognitive function in predicting course of illness over a five year follow-up. We propose to conduct a collaborative study with 168 elderly subjects enrolled in the previous "Treatment Outcomes of Vascular Depression" study at Duke University and Washington University. They will receive follow-up magnetic resonance imaging, neuropsychological testing, and a careful interval history focusing on their depression history, antidepressant use, and medical history to test the hypotheses that: 1) LLD individuals with more depressive episodes over the 5 year longitudinal course will have greater baseline impairment on measures of a) white matter structure b) smaller volumes of the amygdala, hippocampus, and orbitofrontal cortex and c) neuropsychological function; 2) LLD individuals with more depressive episodes over the 5 year longitudinal course will have greater changes on these MRI and neuropsychological test variables over the interim. In secondary aims we will test the effect of the interaction of the measures on depression duration, and examine the effects of connectivity in specific fiber tracts on depression course. The proposal will provide important new data on neuroradiologic and neuropsychological factors contributing to recurrent or chronic depression in older individuals.