Knopik Valerie S, Heath Andrew C, Bucholz Kathleen K, Madden Pamela A F, Waldron Mary
Center for Alcohol and Addiction Studies, Department of Community Health, Brown University Medical School, Box G-S121-4, Providence, RI 02912, United States.
Pharmacol Biochem Behav. 2009 Sep;93(3):313-21. doi: 10.1016/j.pbb.2009.03.011. Epub 2009 Mar 31.
Genetic and environmental contributions to the observed correlations among DSM-IV ADHD problems [inattentive (INATT) and hyperactive/impulsive (HYP/IMP) behaviors], conduct problems (CDP) and alcohol problems (AlcProb) were examined by fitting multivariate structural equation models to data from the Missouri Adolescent Female Twin Study [N=2892 twins (831 monozygotic pairs, 615 dizygotic pairs)]. Based on results of preliminary regression models, we modified the structural model to jointly estimate (i) the regression of each phenotype on significant familial/prenatal predictors, and (ii) genetic and environmental contributions to the residual variance and covariance. Results suggested that (i) parental risk factors, such as parental alcohol dependence and regular smoking, increase risk for externalizing behavior; (ii) prenatal exposures predicted increased symptomatology for HYP/IMP (smoking during pregnancy), INATT and CDP (prenatal alcohol exposure); (iii) after adjusting for measured familial/prenatal risk factors, genetic influences were significant for HYP/IMP, INATT, and CDP; however, similar to earlier reports, genetic effects on alcohol dependence symptoms were negligible; and (iv) in adolescence, correlated liabilities for conduct and alcohol problems are found in environmental factors common to both phenotypes, while covariation among impulsivity, inattention, and conduct problems is primarily due to genetic influences common to these three behaviors. Thus, while a variety of adolescent problem behaviors are significantly correlated, the structure of that association may differ as a function of phenotype (e.g., comorbid HYP/IMP and CDP vs. comorbid CDP and AlcProb), a finding that could inform different approaches to treatment and prevention.
通过对密苏里青少年女性双胞胎研究[样本量为2892对双胞胎(831对同卵双胞胎,615对异卵双胞胎)]的数据拟合多变量结构方程模型,研究了遗传和环境因素对观察到的《精神疾病诊断与统计手册》第四版(DSM-IV)中多动症问题[注意力不集中(INATT)和多动/冲动(HYP/IMP)行为]、品行问题(CDP)和酒精问题(AlcProb)之间相关性的影响。基于初步回归模型的结果,我们修改了结构模型,以联合估计:(i)每种表型对显著家族性/产前预测因素的回归;以及(ii)遗传和环境因素对残差方差和协方差的影响。结果表明:(i)父母风险因素,如父母酒精依赖和经常吸烟,会增加外化行为的风险;(ii)产前暴露可预测HYP/IMP(孕期吸烟)、INATT和CDP(产前酒精暴露)症状增加;(iii)在调整测量的家族性/产前风险因素后,遗传因素对HYP/IMP、INATT和CDP有显著影响;然而,与早期报告相似,遗传因素对酒精依赖症状的影响可忽略不计;以及(iv)在青春期,品行问题和酒精问题的相关易感性存在于两种表型共有的环境因素中,而冲动性、注意力不集中和品行问题之间的协变主要是由于这三种行为共有的遗传影响。因此,虽然多种青少年问题行为显著相关,但这种关联的结构可能因表型而异(例如,HYP/IMP与CDP共病与CDP与AlcProb共病),这一发现可为不同的治疗和预防方法提供依据。