在健康的成年人中,对大脑中血清素载体水平的遗传贡献
Silvia Elisabetta Portis Bruzzone1,2, Arafat Nasser1, Sagar Sanjay Aripaka1,2
1Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
遗传变异会影响人类大脑中的血清素载体 (5-HTT) 水平. MAOA rs1137070 T-载体显示了较高的大脑5-HTT,这表明血清素神经传递的遗传调节.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学是一种遗传学.
- 精神病学是一个精神病学.
背景情况:
- 血清素转运体 (5-HTT) 调节大脑中的血清素水平,影响神经传递.
- 人类大脑中的5-HTT水平在何种程度上是基因决定的,尚不完全理解.
研究的目的:
- 调查常见的血清素相关遗传变异与人脑中的体内5-HTT水平之间的关联.
- 通过机器学习,探索这些基因变异在5-HTT水平上的预测能力.
主要方法:
- 使用[11C]DASB的正子发射断层扫描 (PET) 用于在140名健康志愿者中对大脑5-HTT水平进行成像.
- 评估了与五种遗传变异的关联:BDNF rs6265,SLC6A4 5-HTTLPR,HTR1A rs6295,HTR2A rs7333412和MAOA rs1137070. 这五种遗传变异的关联是:
- 一个随机森林框架与五倍交叉验证被用于预测建模.
主要成果:
- MAOA rs1137070 T-载体在多个大脑区域中表现出明显更高的脑5-HTT水平 (2-11%的增加) 与C-homozygotes相比.
- 在HTR1A rs6295和HTR2A rs7333412基因型中没有发现显著的关联.
- 之前观察到的BDNF rs6265甲基载体的低皮层5-HTT可用性持续存在.
- 基因型在尾状体中适度改善了5-HTT预测,但在多次比较调整后,这种效应在统计学上没有显著意义.
结论:
- MAOA rs1137070多态性与更高的成人人类大脑5-HTT水平有关.
- 这些发现提供了进一步的证据,即特定的与血清素相关的遗传变异调节了脑中血清素输送器的可用性和神经传递.
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