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ABSTRACT. Objective:We examined the long-term effects of childhood familial and neighborhood risk on adolescent substance use and psychiatric symptomatology. Method: This study used data from an ongoing 2-decade long study that recruited alcoholic and neighborhood control families through fathers' drunk-driving records and door-to-door canvassing in a four county area. The sample included 220 male, initially 3-to 5-year-old children of the participant families, who received inhome assessments at baseline and thereafter at 3-year intervals. Parental lifetime psychopathology and offspring symptomatology at ages 18-20 were assessed by semistructured diagnostic interviews. Census tract variables were used to indicate neighborhood characteristics. Results: The isomorphic parental symptomatology predicted offspring psychopathology. For marijuana-use disorder, major depressive disorder, and nicotine dependence, the other parental comorbidities were also signifi cant predictors. Neighborhood residential instability in childhood contributed to the development of late adolescent alcohol-use disorder, marijuana-use disorder, major depressive disorder, antisocial personality disorder, and nicotine-dependence symptomatology. Although lower family socioeconomic status in childhood contributed to more adolescent marijuana-use disorder, major depressive disorder, and nicotine-dependence symptoms, neighborhood socioeconomic status did not predict adolescent psychopathology. Longitudinal changes in neighborhood environments from early childhood to adolescence had signifi cant effects on alcohol-use disorder, marijuana-use disorder, and major depressive disorder symptoms in late adolescence. A higher frequency of family mobility from early childhood to adolescence predicted more nicotine-dependence symptoms in late adolescence. Conclusions: Findings indicate that parental psychopathology, family socioeconomic status, and neighborhood residential instability are all important risk factors for the development of substance-use disorder and other comorbid psychopathology. Intervention programming might effectively use these early parental psychopathology indicators to identify risk and might target community activity to stabilize the social environment and provide youth services to counteract the effects of family transience. (J. Stud. Alcohol Drugs 70: [489][490][491][492][493][494][495][496][497][498] 2009)

Aims We examined the relationship between alcohol expectancies in childhood and onset of drinking, binge drinking, and drunkenness in adolescence and the influence of drinking onset on expectancy development. Design A prospective, longitudinal study of children assessed for alcohol expectancies and drinking at 4 time points between ages 6 and 17. Setting Community study of families at high risk for alcoholism conducted in a 4-county area in the Midwestern United States. Participants The study involved 614 children; 460 were children of alcoholics and 70% were male. Measurements Expectancies about alcohol effects were measured using the Beverage Opinion Questionnaire and child’s drinking by the Drinking and Drug History - Youth Form. Findings Partial factor invariance was found for expectancy factors from ages 6 to 17. Survival analysis showed that social/relaxation expectancies in childhood predicted time to onset of binge drinking and first time drunk (Wald chi-square, 1 d.f. = 3.8, p < .05 and 5.1, p < .05, respectively). The reciprocal effect was also present; when adolescents began drinking, there was an increase in social/relaxation expectancy and a concomitant increase in slope of the expectancy changes lasting throughout adolescence. Conclusions A reciprocal relationship exists between childhood alcohol expectancies and the development of alcohol involvement. Higher expectancies for positive effects predict earlier onset of problem drinking. Onset of use, in turn, predicts an increase in rate of development of positive expectancies.

BackgroundIn genome-wide association studies (GWAS) for complex diseases, the association between a SNP and each phenotype is usually weak. Combining multiple related phenotypic traits can increase the power of gene search and thus is a practically important area that requires methodology work. This study provides a comprehensive review of existing methods for conducting GWAS on complex diseases with multiple phenotypes including the multivariate analysis of variance (MANOVA), the principal component analysis (PCA), the generalizing estimating equations (GEE), the trait-based association test involving the extended Simes procedure (TATES), and the classical Fisher combination test. We propose a new method that relaxes the unrealistic independence assumption of the classical Fisher combination test and is computationally efficient. To demonstrate applications of the proposed method, we also present the results of statistical analysis on the Study of Addiction: Genetics and Environment (SAGE) data.ResultsOur simulation study shows that the proposed method has higher power than existing methods while controlling for the type I error rate. The GEE and the classical Fisher combination test, on the other hand, do not control the type I error rate and thus are not recommended. In general, the power of the competing methods decreases as the correlation between phenotypes increases. All the methods tend to have lower power when the multivariate phenotypes come from long tailed distributions. The real data analysis also demonstrates that the proposed method allows us to compare the marginal results with the multivariate results and specify which SNPs are specific to a particular phenotype or contribute to the common construct.ConclusionsThe proposed method outperforms existing methods in most settings and also has great applications in GWAS on complex diseases with multiple phenotypes such as the substance abuse disorders.

Aims-Neurocognitive deficits in chronic alcoholic men are well documented and include impairments in memory, visual-spatial processing, problem solving and executive function. The cause of these deficits is unclear, but could include direct effects of alcohol toxicity, pre-existing cognitive deficits that may predispose towards substance abuse, comorbid psychiatric disorders (e.g., depression) and comorbid abuse of substances other than alcohol. For example, cigarette smoking occurs at a much higher rate among persons with alcoholism and has been linked to poor cognitive performance. Until recently, the negative effects of smoking on cognitive function in alcoholism have been ignored.Methods-The effects of alcoholism and smoking are examined in a community recruited sample of alcoholic and non-alcoholic men (N=240) using standard neuropsychological measures and reaction-time measures of executive function. Alcoholism severity was measured as an average of alcoholism diagnoses across the study duration (12 yrs). Smoking was measured in pack-years.Results-Both alcoholism and smoking were negatively correlated with a composite executive function score. For component measures, alcoholism was negatively correlated with a broad range of measures, whereas smoking was negatively correlated with measures that emphasize response speed. In regression analyses, both smoking and alcoholism are significant predictors of executive function composite. However; when IQ is included in the regression analyses, alcoholism severity is no longer a significant predictor.Conclusions-Both smoking and alcoholism were related to executive function. However, the effect of alcoholism on EF was not independent of IQ, suggesting that the alcoholism effect was generalized, perhaps affecting a wide range of cognitive abilities of which executive function is a component. On the other hand, the effect of smoking on measures relying on response speed were NIH Public Access Author ManuscriptAddiction. Author manuscript; available in PMC 2010 January 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript independent of IQ, suggesting a more specific processing speed deficit associated with chronic smoking.Alcohol use disorders (AUD) represent a major public health problem with substantial costs (1;2). Neurocognitive deficits in severe, chronic alcoholic men (3-7) are well documented and include visual-spatial processing, problem solving, memory, and cognitive proficiency (3). Problem solving and higher-order impairments led to theories of frontal lobe dysfunction; recent examinations of neurocognitive function in alcoholics have focused on executive function (8;9) in part because neuroimaging studies have linked alcoholism to changes in brain structure and function, especially the frontal lobes and their connections to other brain areas, including the cerebellum (10-15).Although alcoholism is known to have neuropsychological consequences linked with brain impairment, the direct versus indirect role of alcohol toxicity...