Disrupted functional connectivity of the habenula links psychomotor retardation and deficit of verbal fluency and working memory in late-life depression

作者：Su, Ting; Chen, Ben; Yang, Mingfeng; Wang, Qiang; Zhou, Huarong; Zhang, Min; Wu, Zhangying; Lin, Gaohong; Wang, Danpeng; Li, Yue; Zhong, Xiaomei^*; Ning, Yuping^*

来源：CNS Neuroscience & Therapeutics, 2023.

DOI：10.1111/cns.14490

• cognitive impairment
• functional connectivity
• habenula
• late-life depression
• MRI
• verbal fluency
• working memory

BackgroundFunctional abnormalities of the habenula in patients with depression have been demonstrated in an increasing number of studies, and the habenula is involved in cognitive processing. However, whether patients with late-life depression (LLD) exhibit disrupted habenular functional connectivity (FC) and whether habenular FC mediates the relationship between depressive symptoms and cognitive impairment remain unclear.MethodsOverall, 127 patients with LLD and 75 healthy controls were recruited. The static and dynamic FC between the habenula and the whole brain was compared between LLD patients and healthy controls, and the relationships of habenular FC with depressive symptoms and cognitive impairment were explored by correlation and mediation analyses.ResultsCompared with the controls, patients with LLD exhibited decreased static FC between the right habenula and bilateral inferior frontal gyrus (IFG); there was no significant difference in dynamic FC of the habenula between the two groups. Additionally, the decreased static FC between the right habenula and IFG was associated with more severe depressive symptoms (especially psychomotor retardation) and cognitive impairment (language, memory, and visuospatial skills). Last, static FC between the right habenula and left IFG partially mediated the relationship between depressive symptoms (especially psychomotor retardation) and cognitive impairment (verbal fluency and working memory).ConclusionsPatients with LLD exhibited decreased static FC between the habenula and IFG but intact dynamic FC of the habenula. This decreased static FC mediated the relationship between depressive symptoms and cognitive impairment. @@@ Patients with late-life depression (LLD) exhibited decreased static FC between the right habenula and bilateral IFG compared with healthy controls, and this decreased FC was involved in the underlying pathway connecting psychomotor retardation and deficit of verbal fluency and working memory. The present results provide a more in-depth understanding of their pathological mechanism, and could inform the development of more targeted and effective therapeutic interventions, improving the management and treatment outcomes for LLD.image

• 单位
  南方医科大学; 1; 广州医学院