Ageing Brain Centre, Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Sydney, NSW, Australia.
Prog Neurobiol. 2012 Jul;98(1):99-143. doi: 10.1016/j.pneurobio.2012.05.009. Epub 2012 May 17.
As the population ages, the economic and societal impacts of neurodegenerative and neuropsychiatric disorders are expected to rise sharply. Like dementia, late-life depressive disorders are common and are linked to increased disability, high healthcare utilisation, cognitive decline and premature mortality. Considerable heterogeneity in the clinical presentation of major depression across the life cycle may reflect unique pathophysiological pathways to illness; differentiating those with earlier onset who have grown older (early-onset depression), from those with illness onset after the age of 50 or 60 years (late-onset depression). The last two decades have witnessed significant advances in our understanding of the neurobiology of early- and late-onset depression, and has shown that disturbances of fronto-subcortical functioning are implicated. New biomedical models extend well beyond perturbations of traditional monoamine systems to include altered neurotrophins, endocrinologic and immunologic system dysfunction, inflammatory processes and gene expression alterations. This more recent research has highlighted that a range of illness-specific, neurodegenerative and vascular factors appear to contribute to the various phenotypic presentations. This review highlights the major features of late-life depression, with specific reference to its associated aetiological, clinical, cognitive, neuroimaging, neuropathological, inflammatory and genetic correlates. Data examining the efficacy of pharmacological, non-pharmacological and novel treatments for depression are discussed. Ultimately, future research must aim to evaluate whether basic biomedical knowledge can be successfully translated into enhanced health outcomes via the implementation of early intervention paradigms.
随着人口老龄化，神经退行性和神经精神疾病对经济和社会的影响预计将急剧上升。与痴呆症一样，老年期抑郁障碍很常见，并且与残疾增加、高医疗保健利用率、认知能力下降和过早死亡有关。在整个生命周期中，重度抑郁症的临床表现存在相当大的异质性，这可能反映出疾病的独特病理生理途径；将那些发病较早但年龄较大的人（早发性抑郁症）与那些发病年龄在 50 岁或 60 岁以后的人（晚发性抑郁症）区分开来。在过去的二十年中，我们对早发性和晚发性抑郁症的神经生物学有了更深入的了解，并表明额皮质下功能障碍与疾病有关。新的生物医学模型不仅超越了传统单胺系统的干扰，还包括神经生长因子的改变、内分泌和免疫功能障碍、炎症过程和基因表达改变。最近的研究强调，一系列特定于疾病的、神经退行性的和血管因素似乎与各种表型表现有关。本综述重点介绍了老年期抑郁症的主要特征，并特别提到了其相关的病因、临床、认知、神经影像学、神经病理学、炎症和遗传相关性。本文还讨论了检查抗抑郁药、非药物和新型治疗方法疗效的数据。最终，未来的研究必须旨在评估基础生物医学知识是否可以通过实施早期干预模式成功转化为改善健康结果。
