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晚年抑郁症发病机制中的作用。有人提出，血管疾病影响参与情绪调节的白质通路和皮层下结构，并与认知功能下降和治疗抵抗有关。虽然已经描述了一些横断面观察结果，但尚不清楚这些异常如何预测纵向病程。此外，白质病理与包括眶额皮质、杏仁核、海马和基底神经节在内的重要灰质结构变化之间的相互作用尚未得到充分研究。该研究将对美国国立卫生研究院资助的“血管性抑郁症的治疗结果”研究中招募的一组明确的晚年抑郁症（LLD）受试者进行随访。在这项研究中，我们发现了基线认知和结构测量与抗抑郁药的急性反应之间的联系。在目前的建议中，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查基线神经影像学结果和认知功能在预测五年随访过程中的作用。我们建议在杜克大学和华盛顿大学之前的“血管性抑郁症的治疗结果”研究中招募168名老年受试者进行合作研究。他们将接受后续的磁共振成像、神经心理测试，并仔细记录他们的抑郁史、抗抑郁药使用情况和病史，以检验以下假设：1)5年纵向病程中抑郁发作次数较多的LLD个体在a)白质结构、b)杏仁核、海马体和眶额皮质体积较小以及c)神经心理功能方面的基线损害更大；2)在5年的纵向病程中，抑郁发作次数较多的LLD个体在这些MRI和神经心理学测试变量上的变化更大。在次要目标中，我们将测试这些措施的相互作用对抑郁持续时间的影响，并检查特定纤维束的连通性对抑郁病程的影响。该提案将为老年人复发性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.