Department of Psychology, University of Minnesota, Elliott Hall, 75 East River Road, Minneapolis, MN, 55455, USA.
Behav Genet. 2010 Mar;40(2):186-200. doi: 10.1007/s10519-010-9343-3. Epub 2010 Feb 13.
Abnormalities in electrophysiological measures of stimulus-evoked brain activity (including the P3 event-related potential (ERP) and its associated delta and theta time-frequency (TF) components), and intrinsic, resting state brain activity (including EEG in the beta frequency band) have each been associated with biological vulnerability to a variety of externalizing (EXT) spectrum disorders, such as substance use disorders, conduct disorder, and antisocial behavior. While each of these individual measures has shown promise as an endophenotype for one or more aspects of EXT, we proposed that the power to identify EXT-related genes may be enhanced by using these measures collectively. Thus, we sought to explore a multivariate approach to identifying electrophysiological endophenotypes related to EXT, using measures identified in the literature as promising individual endophenotypes for EXT. Using data from our large twin sample (634 MZ and 335 DZ, male and female same-sex pairs), and fitting multivariate biometric Cholesky models, we found that these measures (1) were heritable, (2) showed significant phenotypic and genetic correlation with a general vulnerability to EXT (which is itself highly heritable), (3) showed modest phenotypic and genetic correlation with each other, and (4) were sensitive to genetic effects that differed as a function of gender. These relationships suggest that these endophenotypes are likely tapping into neurophysiological processes and genes that are both common across them and unique to each-all of which are relevant to a biological vulnerability to EXT psychopathology.
电生理测量中刺激诱发脑活动（包括 P3 事件相关电位（ERP）及其相关的德尔塔和θ时间频率（TF）成分）和内在的静息态脑活动（包括β频带的 EEG）的异常，都与各种外化（EXT）谱障碍（如物质使用障碍、品行障碍和反社会行为）的生物易感性有关。虽然这些个体测量中的每一个都显示出作为一个或多个 EXT 方面的内表型的潜力，但我们提出，通过共同使用这些测量，可以增强识别与 EXT 相关的基因的能力。因此，我们试图探索一种多变量方法来识别与 EXT 相关的电生理内表型，使用文献中确定的有前途的 EXT 个体内表型测量。使用我们的大型双胞胎样本（634 对同卵双胞胎和 335 对异卵双胞胎，男性和女性同性对）的数据，并拟合多变量生物计量 Cholesky 模型，我们发现这些测量值（1）是可遗传的，（2）与 EXT 的一般易感性（本身具有高度遗传性）表现出显著的表型和遗传相关性，（3）彼此之间表现出适度的表型和遗传相关性，（4）对性别作为函数的遗传效应敏感。这些关系表明，这些内表型可能涉及到神经生理过程和基因，这些过程和基因在它们之间是共同的，而且对每个内表型都是独特的——所有这些都与 EXT 精神病理学的生物易感性有关。
