大脑结构功能连接性解的表观遗传分子基础在患有严重抑郁症的患者中
Lili Tang1, Pengfei Zhao2, Chunyu Pan3
1Early Intervention Unit, Department of Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, PR China; Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, PR China.
大型抑郁症 (MDD) 涉及到大脑网络动态的改变. HPA轴的表观遗传变化与MDD患者的这些结构功能连接 (SC-FC) 合变化有关.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 精神病学是一个精神病学.
背景情况:
- 大型抑郁症 (MDD) 越来越多地被理解为一种与压力相关的疾病,其特征是异常的大脑网络动态.
- 这些动态大脑网络与它们的分子基础之间的相互作用,特别是表观遗传修饰,尚未得到充分理解.
研究的目的:
- 研究大脑中的结构功能连接 (SC-FC) 合与MDD患者关键HPA轴基因的表观遗传变化之间的关系.
- 探索关联慢性压力,大脑网络功能障碍和MDD易感性的分子机制.
主要方法:
- 从183名MDD患者和300名健康对照者的神经成像数据分析了结构性和功能性脑网络.
- 结构功能连接 (SC-FC) 合被评估在整个大脑 (连接体) 和个别区域 (节点) 层面.
- 五个HPA轴基因 (NR3C1,FKBP5,CRHBP,CRHR1,CRHR2) 的甲基化模式使用Illumina甲基化EPIC BeadChip进行了分析.
主要成果:
- 与对照组相比,MDD患者在连接体水平上显著减少了SC-FC合.
- 节点分析显示了SC-FC合的不平衡,皮层区域的合减少,皮层下区域的合增加.
- 在HPA轴中确定了23个差异甲基化的CpG位点,NR3C1,FKBP5,CRHR1和CRHR2的特定位点与MDD中的SC-FC合有显著的关联.
结论:
- 在HPA轴上的表观遗传修饰与MDD中的宏观大脑网络改变有关.
- 这些发现阐明了在慢性压力下导致MDD易受影响的机制.
- 与HPA轴相关的表观遗传标可能为MDD治疗提供新的治疗途径.
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