Vascular Depression: Longitudinal Followup

描述（由申请人提供）：大量研究支持血管疾病在老年抑郁症发病机制中的作用。已经提出血管疾病影响参与情绪调节的白色物质通路和皮质下结构，并且与较差的认知功能和治疗抗性相关。虽然已经描述了一些横截面观察结果，但尚不清楚这些异常如何预测纵向过程。此外，还没有充分研究白色物质病理学与重要灰质结构（包括眶额皮质、杏仁核、海马和基底神经节）的结构变化之间的相互作用。该研究将随访一个明确定义的老年抑郁症（LLD）受试者队列，这些受试者是为NIH资助的“血管性抑郁症的治疗结果”研究招募的。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急性反应之间的关联。在目前的建议中，我们将扩展这些发现，以确定其对抑郁症纵向过程的影响。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疾病过程中的作用，为期五年的随访。我们建议对168名老年受试者进行一项合作研究，这些受试者参加了杜克大学和华盛顿大学先前的“血管性抑郁症的治疗结局”研究。他们将接受随访磁共振成像，神经心理学测试，以及仔细的间隔史，重点是他们的抑郁史，抗抑郁药使用和病史，以测试以下假设：1）在5年纵向病程中具有更多抑郁发作的LLD个体将在a）白色物质结构B）杏仁核、海马体的较小体积，和眶额皮质和c）神经心理功能; 2）在5年纵向病程中抑郁发作较多的LLD个体在这些MRI和神经心理测试变量上的变化更大。在第二个目标，我们将测试抑郁持续时间的措施的相互作用的效果，并检查在特定的纤维束的连接抑郁症的过程中的影响。该提案将提供重要的新数据，神经放射学和神经心理学因素有助于复发或慢性抑郁症的老年人。

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.