Department of Mental Health and Psychiatry, Faculty of Medicine, University Hospitals of Geneva, University of Geneva, Chêne-Bourg, Switzerland.
Acta Neuropathol. 2012 Oct;124(4):453-64. doi: 10.1007/s00401-012-1021-5. Epub 2012 Jul 27.
A first episode of depression after 65 years of age has long been associated with both severe macrovascular and small microvascular pathology. Among the three more frequent forms of depression in old age, post-stroke depression has been associated with an abrupt damage of cortical circuits involved in monoamine production and mood regulation. Late-onset depression (LOD) in the absence of stroke has been related to lacunes and white matter lesions that invade both the neocortex and subcortical nuclei. Recurrent late-life depression is thought to induce neuronal loss in the hippocampal formation and white matter lesions that affect limbic pathways. Despite an impressive number of magnetic resonance imaging (MRI) studies in this field, the presence of a causal relationship between structural changes in the human brain and LOD is still controversial. The present article provides a critical overview of the contribution of neuropathology in post-stroke, late-onset, and late-life recurrent depression. Recent autopsy findings challenge the role of stroke location in the occurrence of post-stroke depression by pointing to the deleterious effect of subcortical lacunes. Despite the lines of evidences supporting the association between MRI-assessed white matter changes and mood dysregulation, lacunes, periventricular and deep white matter demyelination are all unrelated to the occurrence of LOD. In the same line, neuropathological data show that early-onset depression is not associated with an acceleration of aging-related neurodegenerative changes in the human brain. However, they also provide data in favor of the neurotoxic theory of depression by showing that neuronal loss occurs in the hippocampus of chronically depressed patients. These three paradigms are discussed in the light of the complex relationships between psychosocial determinants and biological vulnerability in affective disorders.
65 岁以后首次出现的抑郁症长期以来一直与严重的大血管和小微血管病理学有关。在老年人群中三种较为常见的抑郁症形式中，中风后抑郁症与涉及单胺产生和情绪调节的皮质回路的突然损伤有关。无中风的晚发性抑郁症（LOD）与侵犯皮质和皮质下核的腔隙和白质病变有关。复发性老年期抑郁症被认为会导致海马体形成中的神经元丧失以及影响边缘通路的白质病变。尽管在这一领域进行了大量磁共振成像（MRI）研究，但大脑结构变化与 LOD 之间存在因果关系的说法仍存在争议。本文批判性地综述了神经病理学在后发性中风、晚发性和复发性老年期抑郁症中的作用。最近的尸检发现挑战了中风位置在中风后抑郁症发生中的作用，指出了皮质下腔隙的有害影响。尽管有大量证据支持 MRI 评估的白质变化与情绪失调之间的关联，但腔隙、脑室周围和深部白质脱髓鞘与 LOD 的发生无关。同样，神经病理学数据表明，早发性抑郁症与人类大脑中与年龄相关的神经退行性变化的加速无关。然而，它们也通过显示慢性抑郁患者的海马体中存在神经元丧失，为抑郁症的神经毒性理论提供了数据。这三个范例是根据情感障碍的社会心理决定因素和生物脆弱性之间的复杂关系来讨论的。
