Amyloid Hypothesis: Is There a Role for Antiamyloid Treatment in Late-Life Depression?
Amyloid Hypothesis: Is There a Role for Antiamyloid Treatment in Late-Life Depression?
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DOI：
10.1016/j.jagp.2015.12.003
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Alexopoulos GS
中科院分区：
文献类型：
--
作者：
Mahgoub N;Alexopoulos GS
抗抑郁药对老年抑郁症的疗效有限，这可能是因为各种神经生物学过程损害了抗抑郁反应所需的额边缘网络。我们认为，淀粉样蛋白的积累是一个病因学因素额边缘妥协，易患抑郁症，并增加治疗阻力，在一个亚组的老年人。在没有抑郁症病史的患者中，阿尔茨海默病临床前阶段的淀粉样蛋白积累可能导致认知障碍之前的前驱抑郁综合征。在早发性抑郁症患者中，反复发作期间的病理生理学变化可能促进淀粉样蛋白积聚，进一步损害抗抑郁反应所需的神经回路，并在连续抑郁发作期间增加治疗抵抗。以下研究结果支持老年抑郁症的淀粉样蛋白假说：a）抑郁症是阿尔茨海默病的危险因素、前驱症状和常见行为表现; B）淀粉样蛋白沉积发生在抑郁症普遍存在的长的痴呆前期; c）有抑郁症终身史的患者在与情绪调节相关的脑区域中具有显著的淀粉样蛋白积累; d）淀粉样蛋白沉积导致神经生物学过程，包括血管损伤、神经退行性变、神经炎症、功能连接中断，其损害与抑郁症有关的网络。老年抑郁症的淀粉样蛋白假说是及时的，因为配体的可用性允许在人脑中对淀粉样蛋白进行体内评估，许多抗淀粉样蛋白药物相对安全，并且有证据表明一些抗抑郁药可能减少淀粉样蛋白的产生。一个引入淀粉样蛋白作用的晚年抑郁模型可能会指导旨在确定新的抗抑郁方法以及阿尔茨海默病预防策略的研究设计。
Antidepressants have modest efficacy in late-life depression, perhaps because various neurobiological processes compromise frontolimbic networks required for antidepressant response. We propose that amyloid accumulation is an etiological factor for frontolimbic compromise that predisposes to depression and increases treatment resistance in a subgroup of older adults. In patients without history of depression, amyloid accumulation during the preclinical phase of Alzheimer’s disease may result in the prodromal depression syndrome that precedes cognitive impairment. In patients with early-onset depression, pathophysiological changes during recurrent episodes may promote amyloid accumulation, further compromise neurocircuitry required for antidepressant response and increase treatment resistance during successive depressive episodes. The following findings support the amyloid hypothesis of late-life depression: a) Depression is a risk factor, a prodrome, and a common behavioral manifestation of Alzheimer’s disease; b) Amyloid deposition occurs during a long pre-dementia period when depression is prevalent; c) Patients with lifetime history of depression have significant amyloid accumulation in brain regions related to mood regulation; d) Amyloid deposition leads to neurobiological processes, including vascular damage, neurodeheneration, neuroinflammation, disrupted functional connectivity, that impair networks implicated in depression. The amyloid hypothesis of late-life depression is timely, because availability of ligands allows in vivo assessment of amyloid in the human brain, a number of anti-amyloid agents are relatively safe, and there is evidence that some antidepressants may reduce amyloid production. A model of late-life depression introducing the role of amyloid may guide the design of studies aiming to identify novel antidepressant approaches as well as prevention strategies of Alzheimer’s disease.
影响因子：
2.4
作者：
Ji W;Ha I
通讯作者：
Ha I