注意力不足過動症：從行為表現型到內在表現型與基因型

Attention Deficit Hyperactivity Disorder: from Behavioral Phenotypes to Endophenotypes and Genotypes

注意力不足過動症（attention-deficit/hyperactivity disorder，簡稱ADHD）是兒童青少年精神疾病中一個常見的臨床問題，對個人的學業、工作及人際關係等層面會產生極大的影響。目前分子基因與影像醫學的研究進展迅速，讓我們可以從行為表現型，深入到內在表現型與基因型的探索，以致更進一步了解ADHD 的致病機轉。在神經心理學方面，目前研究顯示與ADHD 最有關連性的障礙包括抑制功能、工作記憶、延遲嫌惡、視覺記憶、以及時間知覺。在神經生理學方面，包含大腦皮質、神經聯結、以及腦部電生理方面的異常。在神經影像學方面，ADHD 患者最常被報告異常的區域為前額葉、紋狀體以及小腦。動物研究顯示ADHD 的症狀與單胺（monoaminergic）神經傳導系統異常有關，而最具代表性的ADHD 動物模式則是spontaneously hypertensive rats（SHR）。目前用來尋找ADHD 致病基因的方法，包含相關性分析（association analysis），全基因體掃描（genome-wide scan），以及複製數變異（copy number variation, CNV）等。未來仍需要進一步的探索，並整合各個層面的研究結果，以期能全面了解ADHD 的基因型、內在表現型與行為表現型之間的關係。

Attention deficit hyperactivity disorder (ADHD) is a common childhood psychiatric disorder, and has significant influence on the academic performance, occupational function, and interpersonal relationship of individuals with this disorder. Because of the advancement in research on the molecular genetics and imaging medicine, we can explore the mechanisms underlying ADHD from behavioral phenotypes to endophenotypes and genotypes, which can enhance our understanding of the pathophysiology of ADHD. Researches on the neuropsychology have shown that impairments in response inhibition, working memory, delay aversion, visual memory, and time perception are associated with ADHD. In neurophysiology, previous studies have demonstrated abnormality in cerebral cortex, neural connectivity, and electrophysiology in the brain. The majority of neuroimaging studies have found abnormality in prefrontal lobe, striatum, and cerebellum. Researches on animal models have shown that behavioral symptoms of ADHD are related to dysfunction in monoaminergic neurotransmitter systems. Spontaneously hypertensive rats (SHR) are the representative animal model for ADHD. Several methods have been used to detect the risk genes of ADHD, including association analysis, genome-wide scan, and copy number variation (CNV). Future studies with multidisciplinary approach are needed to integrate the results from neuropsychology, neurophysiology, neuroimaging, animal models, and genetics, and thus we are able to obtain more comprehensive understanding of the relationship among genotypes, endophenotypes, and behavioral phenotypes for ADHD.