Department of Psychiatry, University of Pittsburgh, 3811 O' Hara Street, Pittsburgh 15213, PA, USA; Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Psychiatry, University of Pittsburgh, 3811 O' Hara Street, Pittsburgh 15213, PA, USA.
Psychiatry Res Neuroimaging. 2019 Apr 30;286:31-38. doi: 10.1016/j.pscychresns.2019.03.006. Epub 2019 Mar 8.
Dopaminergic alteration is a prominent feature in those with AD and may influence brain development in those with a family history of AD. MRI scans (3T) from 43 HR offspring (27.4 ± 3.6 years) and 45 controls (24.5 ± 4.1 years) provided whole brain (WB) and region of interest (ROI) analyses. The VBM8 toolbox was used for WB analysis (threshold p < 0.005; cluster = 100 voxels); the MarsBaR ROI toolbox provided region of interest data. Pyrosequencing of CpG sites within the DRD2 gene was performed. DRD2 methylation was significantly increased in association with familial high-risk status. Significant familial risk group differences were seen with HR individuals showing reduced volume of the Left Inferior Temporal, Left Fusiform and Left Insula regions relative to LR controls. These regions have previously been linked to social cognition. DRD2 methylation was negatively related to grey matter volumes in these regions. Because these regions, have been previously linked to facial affect perception and social cognition, lesser grey matter volumes in individuals at high-risk for developing AD suggests that neural underpinnings of social cognitive impairment may be a premorbid risk factors for AD.
多巴胺能改变是 AD 患者的一个突出特征，可能会影响有 AD 家族史的人的大脑发育。对 43 名 HR 后代（27.4±3.6 岁）和 45 名对照（24.5±4.1 岁）的 3T MRI 扫描进行了全脑（WB）和感兴趣区（ROI）分析。使用 VBM8 工具箱进行全脑分析（阈值 p<0.005；簇=100 体素）；MarsBaR ROI 工具箱提供了 ROI 数据。对 DRD2 基因内的 CpG 位点进行焦磷酸测序。DRD2 甲基化与家族高风险状态显著相关。与 LR 对照相比，HR 个体的左侧颞下回、左侧梭状回和左侧脑岛的体积明显减少，与家族高风险状态有关。这些区域以前与社会认知有关。DRD2 甲基化与这些区域的灰质体积呈负相关。由于这些区域以前与面部情感感知和社会认知有关，AD 高风险个体的灰质体积较小表明，社会认知障碍的神经基础可能是 AD 的潜在危险因素。
