Department of Psychiatry, Rambam Health Care Campus, Haifa, Israel; Department of Neuroscience, Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, United States of America.
Department of Psychiatry, Rambam Health Care Campus, Haifa, Israel; Department of Physical Therapy, The Stanley Steer School of Health Professions, Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel; Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
J Affect Disord. 2025 Jan 15;369:1013-1020. doi: 10.1016/j.jad.2024.10.077. Epub 2024 Oct 22.
Depression is a heterogeneous disorder, both in terms of patient symptomatology and in patient sociodemographic factors. Here, we examine the contribution of age to this heterogeneity, by characterizing the associations of depressive symptoms with cognitive performance and brain structure across the lifespan. We analyzed data from the Cambridge Centre for Aging Neuroscience (Cam-CAN) cohort (N = 2591, age 18-99). A subset of this cohort (N = 647) underwent structural MRI. Depressive symptoms were measured using the Hospital Anxiety and Depression Scale. Cognitive assessments were performed using The Addenbrooke's Cognitive Examination Revised. Generalized linear models were employed to examine the relationship between depressive symptoms and cognitive performance. Statistical parametric mapping explored age-dependent associations between depressive symptoms and grey matter volume. Cognitive performance was associated with a significant age by depression by cognitive domain interaction, indicating that older individuals with more depressive symptoms had a lower cognitive performance, particularly in the fluency domain. Structural MRI revealed preferential depression-related reduction in grey matter volume in the left and right hippocampi in older adults. By contrast, in younger adults, depressive symptoms were more strongly associated with grey matter volume reduction in the left superior frontal gyrus and left middle frontal gyrus. Collectively, these findings indicate that the associations of depression with cognitive performance and brain structure are age-dependent, suggesting that the pathophysiological mechanisms underlying depression may differ between young and older adults. Recognizing these differences will support the development of better diagnostic tools and therapeutic interventions for depression across the lifespan.
抑郁症是一种异质性疾病，无论是在患者的症状表现还是患者的社会人口学因素方面均是如此。在这里，我们通过研究抑郁症状与认知表现和大脑结构在整个生命周期中的关联，来考察年龄对此种异质性的影响。我们分析了剑桥老龄化神经科学中心（Cam-CAN）队列（N=2591，年龄 18-99 岁）的数据。该队列的一部分（N=647）接受了结构磁共振成像（MRI）检查。使用医院焦虑和抑郁量表（HADS）来测量抑郁症状。使用 Addenbrooke 认知测验修订版（ACE-R）进行认知评估。使用广义线性模型来研究抑郁症状与认知表现之间的关系。统计参数映射（SPM）探索了抑郁症状与灰质体积之间的年龄依赖性关联。认知表现与抑郁症状与认知域的交互作用呈显著的年龄依赖性相关，这表明抑郁症状更严重的老年人认知表现更差，尤其是在流畅性领域。结构 MRI 显示，在老年人中，左、右海马体的灰质体积与抑郁相关的减少呈优先关系。相比之下，在年轻成年人中，抑郁症状与左额上回和左额中回灰质体积减少的相关性更强。综上所述，这些发现表明，抑郁与认知表现和大脑结构的关联是年龄依赖性的，这表明抑郁的病理生理机制在年轻人和老年人中可能存在差异。认识到这些差异将有助于开发针对整个生命周期的抑郁症的更好的诊断工具和治疗干预措施。
