Section for Neurophysiology and Neuroimaging, Laboratory of Neuroscience, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University, Frankfurt, Germany.
Prog Neurobiol. 2011 Dec;95(4):703-17. doi: 10.1016/j.pneurobio.2011.08.001. Epub 2011 Aug 12.
Major depressive disorders (MDD) are among the most debilitating diseases worldwide and occur with a high prevalence in elderly individuals. Neurodegenerative diseases (in particular Alzheimer's disease, AD) do also show a strong age-dependent increase in incidence and prevalence among the elderly population. A high number of geriatric patients with MDD show cognitive deficits and a very high proportion of AD patients present co-morbid MDD, which poses difficult diagnostic and prognostic questions. Especially in prodromal and in very early stages of AD, it is almost impossible to differentiate between pure MDD and MDD with underlying AD. Here, we give a comprehensive review of the literature on the current state of candidate biomarkers for MDD ("positive MDD markers") and briefly refer to established and validated diagnostic AD biomarkers in order to rule out underlying AD pathophysiology in elderly MDD subjects with cognitive impairments ("negative MDD biomarkers"). In summary, to date there is no evidence for positive diagnostic MDD biomarkers and the only way to delineate MDD from AD is to use "negative MDD" biomarkers. Because of this highly unsatisfactory current state of MDD biomarker research, we propose a research strategy targeting to detect and validate positive MDD biomarkers, which is based on a complex (genetic, molecular and neurophysiological) biological model that incorporates current state of the art knowledge on the pathobiology of MDD. This model delineates common pathways and the intersection between AD and MDD. Applying these concepts to MDD gives hope that positive MDD biomarkers can be successfully identified in the near future.
重度抑郁症（MDD）是全球最具致残性的疾病之一，在老年人中发病率很高。神经退行性疾病（特别是阿尔茨海默病，AD）也在老年人群中表现出发病率和患病率的强年龄依赖性增加。大量患有 MDD 的老年患者表现出认知缺陷，而相当高比例的 AD 患者存在共病 MDD，这给诊断和预后带来了困难。特别是在 AD 的前驱期和早期阶段，几乎不可能区分单纯的 MDD 和有潜在 AD 的 MDD。在这里，我们对 MDD 的候选生物标志物（“阳性 MDD 标志物”）的文献进行了全面综述，并简要提到了已建立和验证的 AD 诊断生物标志物，以排除有认知障碍的老年 MDD 患者中潜在的 AD 病理生理学（“阴性 MDD 标志物”）。总的来说，迄今为止，没有证据表明存在阳性的 MDD 诊断生物标志物，将 MDD 与 AD 区分开来的唯一方法是使用“阴性 MDD”生物标志物。由于 MDD 生物标志物研究目前的状况非常令人不满意，我们提出了一种研究策略，旨在检测和验证阳性 MDD 生物标志物，该策略基于一个复杂的（遗传、分子和神经生理学）生物模型，该模型结合了 MDD 病理生理学的最新知识。该模型描绘了 AD 和 MDD 的共同途径和交叉点。将这些概念应用于 MDD 研究有望在不久的将来成功识别出阳性 MDD 生物标志物。
