Frederick Jon A, Iacono William G
Department of Psychology, University of Minnesota, 75 East River Road, Minneapolis, MN 55455, USA.
Curr Psychiatry Rep. 2006 Apr;8(2):144-50. doi: 10.1007/s11920-006-0014-2.
Although substance-related disorders are heritable, the genetic factors contributing to vulnerability to these disorders are expected to be complex. Nonetheless, identifying genes underlying this vulnerability and understanding their relationship with environmental factors and behavior holds the promise of dramatic advances in diagnosis, prevention, and treatment. The search is complicated by a number of factors, however, including the weak validity of psychiatric diagnosis for identifying gene carriers, the complexity of the brain and behavior, and the numerous intervening variables between genetic transcription and its behavioral consequences. One strategy for bridging this theoretical gap is to study endophenotypes--biologic correlates of disorders that precede their overt development, may have higher reliability than behavioral measures, and present simpler relationships with a smaller number of genes. This article reviews research suggesting the usefulness of several putative endophenotypes for substance-related disorders, including 1) reduced P3 amplitude of the visual event-related potential, 2) increased EEG beta power, 3) a lowered level of response to an alcohol challenge, and 4) the inability to modulate autonomic nervous system reactivity under the stress of anticipating a predictable aversive stimulus.
尽管物质相关障碍具有遗传性，但导致易患这些障碍的遗传因素预计是复杂的。然而，识别这种易感性背后的基因并理解它们与环境因素及行为的关系，有望在诊断、预防和治疗方面取得重大进展。然而，这项研究因多种因素而变得复杂，包括用于识别基因携带者的精神科诊断有效性较弱、大脑和行为的复杂性，以及基因转录与其行为后果之间众多的中间变量。弥合这一理论差距的一种策略是研究内表型——在障碍明显发展之前的生物学相关因素，可能比行为测量具有更高的可靠性，并且与较少数量的基因呈现更简单的关系。本文综述了一些研究，这些研究表明几种假定的内表型对物质相关障碍有用，包括：1）视觉事件相关电位的P3波幅降低；2）脑电图β波功率增加；3）对酒精激发的反应水平降低；4）在预期可预测的厌恶刺激的压力下无法调节自主神经系统反应性。
