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融合和分离的基因表达特征与缺陷和非缺陷精神分裂症中大脑功能连接体功能障碍相关

Chao Zhou¹, Xiaowei Tang², Miao Yu³

¹Department of Geriatric Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

Translational psychiatry

|February 27, 2024

概括

这项研究揭示了缺陷精神分裂症 (DS) 和非缺陷精神分裂症 (NDS) 患者的不同大脑功能连接模式,将这些变化与基因表达联系起来. 这些发现为精神分裂症亚型的遗传基础提供了洞察力.

科学领域:

神经科学是一个神经科学.
遗传学是一个遗传学.
精神病学是一个精神病学.

背景情况:

缺陷精神分裂症 (DS) 的特点是持续的负面症状,与非缺陷精神分裂症 (NDS) 相比,已知大脑功能差异.
在DS和NDS中观察到的这些功能性大脑变化的遗传基础在很大程度上仍未被探索.

研究的目的:

在DS和NDS患者中识别功能连接 (FC) 模式的改变.
调查与这些异常FC模式相关的基因表达特征.
探索改变FC的诊断实用性和基础精神分裂症亚型的遗传调节.

主要方法:

基于Voxel的全脑关联研究,检测82个DS,96个NDS和124个健康对照 (CN) 的改变FC.
机器学习用于评估FC的诊断实用性.
在6个捐赠的大脑上进行了权重基因协同表达网络分析 (WGCNA),以将FC与基因表达联系起来.
对遗传资料的丰富分析和时空基因表达分析.

主要成果:

与CN相比,在DS的23个大脑区域和NDS的20个大脑区域中发现了CF的显著变化.
改变的FC与症状严重程度相关,并显示出高的诊断分类效率.
WGCNA确定了与DS/NDS相关的基因表达和改变的FC之间的关联,在亚型之间发现了22个重叠基因.
丰富分析将已识别的基因与细胞反应,神经调节,受体结合和通道活动途径联系起来.

结论:

独特的FC模式区分了DS和NDS,有可能用于诊断分类.
该研究提供了关键的见解,共同和特定的基因调节机制背后的脑功能变化在DS和NDS.
这些发现表明精神分裂症亚型的潜在基因成像病原体.

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