The BDNF Val66Met polymorphism, resting-state hippocampal functional connectivity and cognitive deficits in acute late-onset depression
The BDNF Val66Met polymorphism, resting-state hippocampal functional connectivity and cognitive deficits in acute late-onset depression
复制标题
急性迟发性抑郁症的 BDNF Val66Met 多态性、静息态海马功能连接和认知缺陷
DOI：
10.1016/j.jad.2015.04.050
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发表时间：
2015-09-01
影响因子：
6.6
通讯作者：
Yuan，Yonggui
中科院分区：
文献类型：
--
作者：
Yin，Yingying;Hou，Zhenghua;Yuan，Yonggui
目的探讨急性晚发性抑郁症（LOD）患者海马功能连接（HFC）与认知功能障碍的关系，以及脑源性神经营养因子（BDNF）Val 66 Met基因多态性对HFC的影响。根据是否携带BDNF Met等位基因将LOD组和NC组进一步分为4组（LOD Met-（n=8）; LOD Met+（n=18）; NC Met-（n=9）; NC Met+（n=24））。通过种子相关分析和双因素协方差分析（ANCOVA）探讨LOD和BDNF Val 66 Met多态性对HFC的主效应和交互效应。斯皮尔曼相关性被应用于研究这些改变的HFC网络的认知和情感的意义。结果与NCs相比，双侧正HFC与右侧额叶皮层，左侧正HFC与双侧眶额皮层（OFC）和左侧楔前叶，右侧正HFC与右侧背外侧前额叶皮层（DLPFC）减少，双侧负HFC与右侧中央后回逆转。脑源性神经营养因子Met等位基因主要减少双侧阳性HFC与小脑。LOD和BDNF Met等位基因的交互作用主要影响双侧HFC与颞叶皮质和背侧神经的联系。眶额皮层、中央后回、小脑和颞叶皮质的HFC改变与认知功能的减退显著相关。结论LOD患者、BDNF Met等位基因携带者和携带Met等位基因的LOD患者的认知功能恶化分别与眶额皮层/中央后回、小脑和颞叶皮层HFC网络的改变有关。
ObjectiveTo investigate the relationship between hippocampal functional connectivity (HFC), cognitive deficits, and the influence of BDNF Val66Met polymorphism on the HFC in acute late-onset depression (LOD).Methods26 LOD patients and 33 and normal controls (NCs) completed clinical assessments, neuropsychological testing, blood samples collecting for genotyping, and resting-state functional MRI (R-fMRI) scans. The LOD and NCs groups were further divided into four groups according to BDNF Met allele carrier or not (LOD Met−(n=8); LOD Met+(n=18); NCs Met−(n=9); NCs Met+(n=24)). Then, seed-based correlation analyses and two-way analysis of covariance (ANCOVA) were performed to explore the main effects and interactive effects of LOD and BDNF Val66Met polymorphism on the HFC. Spearman correlation was applied to examine the cognitive and emotional significance of these altered HFC networks.ResultsCompared with NCs, bilateral positive HFC with the right insula, left positive HFC with bilateral orbit-frontal cortex (OFC) and left precuneus, right positive HFC with right dorsolateral prefrontal cortex (dlPFC) were decreased, and bilateral negative HFC with right postcentral gyrus were reversed in LOD patients. BDNF Met allele mainly decreased bilateral positive HFC with the cerebellum. The interaction of LOD and BDNF Met allele primarily influenced the bilateral HFC with the temporal cortex and dorsal nexus. The changed HFC with the OFC, postcentral gyrus, cerebellum and temporal cortex significantly correlated to the cognitive deterioration. There was no significant association between the depressive severity and any altered HFC networks.ConclusionThe cognitive deterioration in LOD patients, BDNF Met allele carriers, and LOD patients carring Met allele were associated with the changed HFC networks in the OFC/postcentral gyrus, cerebellum and temporal cortex respectively.