Developmental Endophenotypes: Indexing Genetic Risk for Substance Abuse With the P300 Brain Event-Related Potential
Developmental Endophenotypes: Indexing Genetic Risk for Substance Abuse With the P300 Brain Event-Related Potential
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DOI：
10.1111/j.1750-8606.2011.00205.x
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发表时间：
2011-12-01
影响因子：
6.4
通讯作者：
Malone, Stephen M.
中科院分区：
文献类型：
--
作者：
Iacono, William G.;Malone, Stephen M.
虽然物质使用障碍（SUD）是可遗传的，但其复杂性使得识别其发展背后的基因具有挑战性。内表型，生物信息的定量措施，指数遗传风险的障碍，正在认识到他们的潜力，以协助寻找疾病相关的基因。在概述了包括发育考虑在内的内表型标准后，本文综述了大脑P300反应如何作为药物滥用和相关外化障碍的遗传风险指数。P300反应具有高度遗传性，并且与外化障碍的特征广泛相关，包括儿童破坏性障碍、反社会性和异常行为的早熟表达。这种关联似乎是由共同的遗传影响介导的。前瞻性研究证实，在大量暴露于成瘾物质之前，年轻人中存在的P300振幅降低与随后的SUD发展相关。尽管在发展过程中的平均水平的显着变化，P300振幅显示出强大的排名顺序稳定性与反复评估，通过年轻的成年。此外，基于多项评估的P300发育轨迹显示出非常高的遗传性，作为遗传风险的衡量标准可能特别有用。总的来说，这些研究结果提供了强有力的支持的想法，P300的幅度和它的变化，通过发展反映了遗传脆弱性药物滥用和相关的外化精神病理学。
Although substance use disorders (SUDs) are heritable, their complexity has made identifying genes underlying their development challenging. Endophenotypes, biologically informed quantitative measures that index genetic risk for a disorder, are being recognized for their potential to assist the search for disorder-relevant genes. After outlining criteria for an endophenotype that includes developmental considerations, this article reviews how the brain P300 response serves as an index of genetic risk for substance abuse and related externalizing disorders. The P300 response is highly heritable and associated broadly with characteristics of externalizing disorder, including childhood disruptive disorders, antisociality, and precocious expression of deviant behavior. This association appears to be mediated by shared genetic influences. Prospective studies confirm that reduced P300 amplitude present in youth prior to significant exposure to addictive substances is associated with the subsequent development of SUDs. Despite pronounced change in mean level over the course of development, P300 amplitude shows strong rank-order stability with repeated assessment through young adulthood. In addition, P300 developmental trajectories based on multiple assessments show very high heritability and may be especially informative as measures of genetic risk. Collectively, these findings provide strong support for the idea that P300 amplitude and its change through development reflect genetic vulnerability to substance abuse and related externalizing psychopathology.