Mol Psychiatry:王晶研究组等发现注意缺陷多动障碍执行抑制缺陷易感基因

2017-05-31 佚名 心理研究所

近日,中国科学院心理研究所王晶研究组与北京大学第六医院王玉凤研究组、北京大学刘东研究组合作,在中国汉族儿童注意缺陷多动障碍(Attention deficit hyperactivity disorder, ADHD)患者中开展了国际首个ADHD执行抑制功能的全基因组关联研究,并发现了新的与ADHD执行抑制相关的易感基因。ADHD是儿童/青少年期常见的行为障碍,患病率在5%左右,其主要表现为与发育

近日,中国科学院心理研究所王晶研究组与北京大学第六医院王玉凤研究组、北京大学刘东研究组合作,在中国汉族儿童注意缺陷多动障碍(Attention deficit hyperactivity disorder, ADHD)患者中开展了国际首个ADHD执行抑制功能的全基因组关联研究,并发现了新的与ADHD执行抑制相关的易感基因。

ADHD是儿童/青少年期常见的行为障碍,患病率在5%左右,其主要表现为与发育不相称的注意力不集中、多动及冲动。ADHD致病机制尚不明确,一般认为是由多种生物因素、心理和社会因素所致的一种综合征。目前候选基因关联研究发现了一些与疾病相关联的基因,但这些基因对疾病的表型变异只有3.3%的影响力,而且只能解释遗传力的4.3%。同时,该病表型复杂、异质性高,因此目前的全基因组关联研究都没有发现显着的疾病易感基因。

已有研究表明,执行抑制功能受损是ADHD患者的核心缺陷。为更加深入了解ADHD的发病原因,研究人员开展了国际上首个ADHD执行抑制功能的两阶段GWAS研究,使用Stroop色字-干扰测验评估1702例病例的执行抑制功能,最终在7p22.3上发现了一个和Stroop测验的词干扰时间显着相关的新的易感位点(rs11514810,Pdiscovery=3.42e-09,Preplication=0.01176,Pcombined=5.249e-09)。同时,网络分析显示大多数与MICALL2 相互作用的基因均与精神疾病相关,而调控特征分析和表达数量性状位点(eQTL)数据显示该位点促成MICALL2 在人脑中的表达。此外,研究发现通过抑制与MICALL2 同源的斑马鱼基因的表达,可诱发多动-冲动样行为,该行为可通过ADHD的临床药物——阿托莫西汀来缓解,从而进一步验证了该基因对ADHD的致病作用。

研究结果表明,在ADHD的多动-冲动行为中,MICALL2 是与执行抑制缺陷相关的新的易感基因,进一步强调了神经发育基因在ADHD的致病机制中的可能作用。执行抑制在精神疾病发病机制研究中扮演了重要角色,该研究作为第一个行为-认知表型层面具有显着结果的GWAS研究,为抑制功能的遗传机制研究提供了重要信息,同时表明从内表型角度入手研究ADHD致病机制会有新的发现。

该研究是王晶研究组同临床医院合作,应用生物信息学方法探索复杂疾病致病机制所取得的系列成果之一。日前,相关论文已经正式发表于《分子精神病学》(Molecular Psychiatry)杂志。

该研究得到科技部、国家自然科学基金委、中科院和北京市科委等项目的资助。

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JAMA Pediatr:ADHD儿童和青少年服用兴奋药物显著降低骨量

鼠研究揭示交感神经系统激活导致骨量减少。用于治疗注意缺陷/多动障碍(ADHD)的兴奋药物增加交感神经张力,并可能影响骨重建。由于骨量增加是在成年早期完成的,所以评估兴奋剂对生长中的儿童骨密度的影响是至关重要的。来自美国的研究人员开展了一项研究,该研究的目的是探讨在儿童和青少年人群中,兴奋药物的使用和骨量之间的关系。该横断面分析使用了在2005年1月1日至2010年12月31日期间国家健康和营养调查

SHP465-306治疗成人ADHD是安全有效的

根据最近一项长达4周的随机、双盲、多中心研究结果,Shire开发的三珠混合苯丙胺盐胶囊三珠混合苯丙胺盐胶囊对注意缺陷多动障碍(ADHD)是安全和有效的。该研究纳入了275名年龄在18岁到55岁之间的ADHD患者,患者随机接受12.5 mg或37.5 mg的SHP465-306,以及安慰剂对照。在4周时,与安慰剂组相比,接受12.5 mg SHP465-306患者的ADHD评定量表总分最小二乘均数差