Discoveries on the Genetics of ADHD in the 21st Century: New Findings and Their Implications.
Discoveries on the Genetics of ADHD in the 21st Century: New Findings and Their Implications.
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21 世纪 ADHD 遗传学发现：新发现及其启示。
DOI：
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发表时间：
2018
影响因子：
17.7
通讯作者：
A. Thapar
中科院分区：
文献类型：
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作者：
A. Thapar
21世纪已经发现了与注意缺陷多动障碍（ADHD）相关的多种罕见和常见的基因变异，这些发现已经为研究该疾病的生物学和新的治疗方法提供了一个起点。这篇选择性综述的目的是检查过去5年的遗传发现，并考虑它们对ADHD概念化和未来临床实践的影响。最近的发现揭示了多动症和自闭症谱系障碍（ASD）以及智力残疾之间强烈的基因重叠。因此，在存在ASD的情况下，删除先前的ADHD诊断排除标准是DSM-5中一个受欢迎的变化。然而，多动症也显示出与更广泛的神经精神疾病以及非精神疾病（如肺癌）的大量遗传相关性。研究这些联系的潜在解释是重要的下一步。ADHD虽然在临床实践中被有效地概念化为一种疾病，但也可以被视为一种特征。最近的全基因组关联研究发现，与双胞胎研究一致，强调ADHD位于连续分布维度的极端末端，类似于高血压沿着血压的连续体。虽然ADHD水平通常会随着年龄的增长而下降，但双胞胎和分子遗传学研究表明，持续的轨迹与较高的遗传负荷有关。尽管许多国家的指导方针建议对轻度智力残疾或ASD患者进行常规检测，但目前还不建议对ADHD患者进行罕见突变的常规检测，因此实践可能会改变。与药物基因组学一样，ADHD常见基因变异的预测能力很弱，因此目前的临床价值有限。1938年11月：行为问题儿童的脑电图分析脑电图是第一个应用于儿童行为障碍的生物学技术。贾斯珀、所罗门和布拉德利报告说：“脑电图已经成功地揭示了超过一半的儿童行为障碍患者的大脑功能明显异常，而这些儿童行为障碍在以前被认为主要是由心理因素引起的。”[美国精神病学杂志1938；95:641-658]。
The 21st century has witnessed the discovery of multiple rare and common gene variants associated with attention deficit hyperactivity disorder (ADHD), and these discoveries have already provided a starting point for the investigation of the biology of the disorder and novel treatments. The purpose of this selective review is to examine genetic findings from the past 5 years and consider their implications for the conceptualization of ADHD and future clinical practice. Recent discoveries reveal the strong genetic overlaps between ADHD and autism spectrum disorder (ASD) as well as intellectual disability. Thus, the removal of the previous diagnostic exclusion criteria for ADHD in the presence of ASD is a welcome change in DSM-5. However, ADHD also shows substantial genetic correlations with a much broader group of neuropsychiatric disorders as well as with nonpsychiatric conditions (e.g., lung cancer). Investigating potential explanations for these links is an important next step. ADHD, while usefully conceptualized as a disorder in clinical practice, can be viewed as a trait. Recent genome-wide association study findings, consistent with twin studies, highlight that ADHD lies at the extreme end of a continuously distributed dimension, akin to hypertension along the continuum of blood pressure. Although ADHD levels typically decline with age, twin and molecular genetic studies suggest that a persistent trajectory is associated with higher genetic loading. Routine testing for rare mutations in ADHD is not yet recommended, although guidelines in many countries recommend testing individuals with mild intellectual disability or ASD, so practice could change. Common gene variants for ADHD are only weakly predictive and therefore have limited clinical value at present, as does pharmacogenomics. [AJP at 175: Remembering Our Past As We Envision Our Future November 1938: Electroencephalographic Analyses of Behavior Problem Children The electroencephalogram was the first biological technique to be applied to childhood behavioral disorders. Jasper, Solomon, and Bradley reported that "the electroencephalogram has succeeded in revealing a definite abnormality of brain function in over one half of a group of childhood behavior disorders which had been previously considered as largely psychogenic." (Am J Psychiatry 1938; 95:641-658 )].