Department for Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
International Max Planck Research School: Neuroscience of Communication: Structure, Function, and Plasticity, Leipzig, Germany.
Psychol Med. 2024 Jan;54(1):125-135. doi: 10.1017/S0033291723000697. Epub 2023 Apr 5.
Cumulative burden from vascular risk factors (VRFs) has been associated with an increased risk of depressive symptoms in mid- and later life. It has been hypothesised that this association arises because VRFs disconnect fronto-subcortical white matter tracts involved in mood regulation, which puts older adults at higher risk of developing depressive symptoms. However, evidence for the hypothesis that disconnection of white matter tracts underlies the association between VRF burden and depressive symptoms from longitudinal studies is scarce.
This preregistered study analysed longitudinal data from 6,964 middle-aged and older adults from the UK Biobank who participated in consecutive assessments of VRFs, brain imaging, and depressive symptoms. Using mediation modelling, we directly tested to what extend white matter microstructure mediates the longitudinal association between VRF burden and depressive symptoms.
VRF burden showed a small association with depressive symptoms at follow-up. However, there was no evidence that fractional anisotropy (FA) of white matter tracts mediated this association. Additional analyses also yielded no mediating effects using alternative operationalisations of VRF burden, mean diffusivity (MD) of single tracts, or overall average of tract-based white matter microstructure (global FA, global MD, white matter hyperintensity volume).
Our results lend no support to the hypothesis that disconnection of white matter tracts underlies the association between VRF burden and depressive symptoms, while highlighting the relevance of using longitudinal data to directly test pathways linking vascular and mental health.
血管危险因素（VRF）的累积负担与中年及以后的抑郁症状风险增加有关。有人假设，这种关联是因为 VRF 会使参与情绪调节的额皮质下白质束断开，从而使老年人更容易出现抑郁症状。然而，从纵向研究中得出 VRF 负担与抑郁症状之间存在关联的假设，即白质束的断开是其基础，这方面的证据很少。
这项预先注册的研究分析了来自英国生物库的 6964 名中年及以上成年人的纵向数据，这些成年人连续接受了 VRF、脑成像和抑郁症状评估。使用中介模型，我们直接测试了白质微观结构在多大程度上介导了 VRF 负担与抑郁症状之间的纵向关联。
VRF 负担与随访时的抑郁症状呈轻度相关。然而，没有证据表明白质束的各向异性分数（FA）介导了这种关联。使用 VRF 负担的替代操作化、单束的平均扩散度（MD）或基于束的白质微观结构的整体平均值（全局 FA、全局 MD、白质高信号体积）进行的额外分析也没有中介效应。
我们的结果不支持 VRF 负担与抑郁症状之间存在关联的假设，即白质束的断开是其基础，同时强调了使用纵向数据直接测试血管和心理健康之间关联途径的重要性。
