关联ADHD和皮质醇变异的共同生物学途径与外部化行为有关
João K N Ramos1, Eugenio H Gravet2, Iago Junger-Santos1
1Laboratory of Physiological Genomics of Mental Health (PhysioGen Lab), Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, São Paulo, Brazil.
注意缺陷/多动症 (ADHD) 和早晨皮质醇水平有共同的遗传联系,这表明复杂的兴奋调节而不是直接的因果关系. 这些发现表明共享的基因组结构影响了这两种情况.
科学领域:
- 神经遗传学
- 内分泌学
- 精神病学
背景情况:
- 皮质醇调节的改变与注意力缺陷/多动症 (ADHD) 有关,但因果关系尚不清楚.
- 现有的分析表明,较低的早晨皮质醇水平与ADHD之间存在相关性,尽管研究存在异质性.
研究的目的:
- 通过先进的遗传方法, 研究早晨皮质醇水平与ADHD之间的因果关系和共同的遗传结构.
- 探索特定遗传区域和多基因分数在皮质醇和ADHD之间的关联中的作用.
主要方法:
- 使用孟德尔随机化 (MR) 用七种方法对早晨皮质醇 (n=25,314) 和ADHD (n=225,543) 的大规模遗传数据.
- 在独立的ADHD样本 (n=1660) 中评估了全球和本地遗传相关性,使用了conjFDR方法,并进行了多基因评分 (PGS) 分析.
主要成果:
- 证据表明区域变, 而不是直接的因果关系,
- 在5号和22号染色体上发现了局部遗传相关性, 包括RASGRF2和TRIOBP等基因.
- 皮质醇PGS与欧洲祖先的外化行为并发症有关,并且在调整为精神疾病时显示ADHD病例的值较低.
结论:
- ADHD和皮质醇水平通过复杂的兴奋调节联系在一起, 符合U型关系模式, 而不是简单的应激反应机制.
- 研究结果支持将ADHD视为系统性失调,
- 共同的遗传因素有助于观察到的关联,强调了ADHD遗传与生理之间的复杂相互作用.
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