Search tips
Search criteria


Important Notice

PubMed Central Canada to be taken offline in February 2018

On February 23, 2018, PubMed Central Canada (PMC Canada) will be taken offline permanently. No author manuscripts will be deleted, and the approximately 2,900 manuscripts authored by Canadian Institutes of Health Research (CIHR)-funded researchers currently in the archive will be copied to the National Research Council’s (NRC) Digital Repository over the coming months. These manuscripts along with all other content will also remain publicly searchable on PubMed Central (US) and Europe PubMed Central, meaning such manuscripts will continue to be compliant with the Tri-Agency Open Access Policy on Publications.

Read more

Results 1-21 (21)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  Comparison of parent, peer, psychiatric, and cannabis use influences across stages of offspring alcohol involvement: Evidence from the COGA Prospective Study 
All stages of development of alcohol use disorder (AUD) have not been equally studied. While initiation of drinking has been given considerable attention, other stages have not been as thoroughly investigated. It is not clear if the same factors are associated consistently across early and late transitions in AUD involvement. High risk family samples that are enriched for AUD vulnerability and transitions in AUD development offer an opportunity to examine influences across multiple stages of AUD development.
Data from adolescents and young adults from high risk families were used to study four transitions in AUD development –time to first drink, first drink to first problem, first drink to first diagnosis, and first problem to first diagnosis. Cox modeling was used to compare associations of parental AUD, parental separation, peer substance use, offspring ever-use of cannabis, trauma exposures and internalizing and externalizing psychopathology across transitions.
Hazards of most transitions were elevated for those who had ever used cannabis, those who attributed substance use to their peers, those with externalizing disorders and those with parents with AUD. Many risk factors were linked to early initiation of alcohol, particularly cannabis use. Internalizing disorders were associated with later stages. Non-assaultive trauma was associated only with early initiation; assaultive trauma was not associated with any transition. .
In this large, ethnically-diverse sample of high risk youth, significant influences across transitions were fairly consistent, with externalizing disorders and cannabis ever-use elevating the likelihood of each stage, and peer and parental (and especially maternal AUD) influences linked to initiation and some later stages. Finally, in light of the increasingly permissive legal and social stances toward cannabis in the U.S., the marked elevations of all alcohol outcomes observed for cannabis use underscore the importance of studying the underpinnings of this relationship.
PMCID: PMC5272776  PMID: 28073157
2.  Reward processing deficits and impulsivity in high-risk offspring of alcoholics: A study of event-related potentials during a monetary gambling task 
Individuals at high risk to develop alcoholism often manifest neurocognitive deficits as well as increased impulsivity. The goal of the present study is to elucidate reward processing deficits, externalizing disorders, and impulsivity as elicited by electrophysiological, clinical and behavioral measures in subjects at high risk for alcoholism from families densely affected by alcoholism in the context of brain maturation across age groups and gender.
Event-related potentials (ERPs) and current source density (CSD) during a monetary gambling task (MGT) were measured in 12–25 year old offspring (N = 1864) of families in the Collaborative Study on the Genetics of Alcoholism (COGA) Prospective study; the high risk (HR, N = 1569) subjects were from families densely affected with alcoholism and the low risk (LR, N = 295) subjects were from community families. Externalizing disorders and impulsivity scores were also compared between LR and HR groups.
HR offspring from older (16–25 years) male and younger (12–15 years) female subgroups showed lower P3 amplitude than LR subjects. The amplitude decrement was most prominent in HR males during the loss condition. Overall, P3 amplitude increase at anterior sites and decrease at posterior areas were seen in older compared to younger subjects, suggesting frontalization during brain maturation. The HR subgroups also exhibited hypofrontality manifested as weaker CSD activity during both loss and gain conditions at frontal regions. Further, the HR subjects had higher impulsivity scores and increased prevalence of externalizing disorders. P3 amplitudes during the gain condition were negatively correlated with impulsivity scores.
Older male and younger female HR offspring, compared to their LR counterparts, manifested reward processing deficits as indexed by lower P3 amplitude and weaker CSD activity, along with higher prevalence of externalizing disorders and higher impulsivity scores.
Reward related P3 is a valuable measure reflecting neurocognitive dysfunction in subjects at risk for alcoholism, as well as to characterize reward processing and brain maturation across gender and age group.
PMCID: PMC4898464  PMID: 26388585
Alcohol use disorders; family history of alcoholism; P3; current source density; reward processing; impulsivity; endophenotype; brain maturation; hypofrontality; frontalization
3.  Alcohol problems in young adults transitioning from adolescence to adulthood: The association with race and gender 
Addictive behaviors  2010;36(3):167-174.
Race and gender may be important considerations for recognizing alcohol related problems in Black and White young adults. This study examined the prevalence and age of onset of individual alcohol problems and alcohol problem severity across race and gender subgroups from a longitudinal study of a community sample of adolescents followed into young adulthood (N = 166; 23–29 yrs. old who were drinkers). All alcohol problems examined first occurred when subjects were in their late teens and early 20s. Drinking in hazardous situations, blackouts, and tolerance were the most common reported alcohol problems. In race and gender comparisons, more males than females experienced alcohol problems. Blacks generally had a later age of onset of alcohol problems. Multivariate regressions showed greater alcohol problem severity in males compared to females, but no significant differences between Blacks and Whites. Education, family environment and earlier alcohol use behaviors and expectancies were reliable predictors of alcohol problem severity in young adulthood. White males were at particular risk for experiencing more severe alcohol problems. Findings may inform the design of more targeted interventions for alcohol problems in different populations.
PMCID: PMC3018558  PMID: 21115225
Alcohol; alcohol problems; race; gender; adolescents; young adults
4.  Development and Vulnerability Factors in Adolescent Alcohol Use 
This article provides an overview of the characteristics of adolescent alcohol use, normative and subgroup variations in drinking behavior, and important factors associated with an increased risk for developing alcohol problems in later adolescence and young adulthood. A parental/family history of alcoholism, temperament traits, conduct problems, cognitive functioning, alcohol expectancies, and peer and other social relations are identified as influencing an adolescent’s susceptibility for initiating a variety of alcohol use behaviors. The Deviance Prone Model, proposed by Sher (1991), is presented as an important tool for testing possible relationships among the various risk factors and their sequencing that leads to early adolescent alcohol and drug initiation and use. It is also possible to extend the model to allow for an examination of the complex interplay of risk factors that leads to the development of alcohol use problems in late adolescence and young adults.
PMCID: PMC2916876  PMID: 20682217
Adolescents; alcohol use; vulnerability factors; deviance proneness
5.  Deficient Event-Related Theta Oscillations in Individuals at Risk for Alcoholism: A Study of Reward Processing and Impulsivity Features 
PLoS ONE  2015;10(11):e0142659.
Individuals at high risk to develop alcoholism often manifest neurocognitive deficits as well as increased impulsivity. Event-related oscillations (EROs) have been used to effectively measure brain (dys)function during cognitive tasks in individuals with alcoholism and related disorders and in those at risk to develop these disorders. The current study examines ERO theta power during reward processing as well as impulsivity in adolescent and young adult subjects at high risk for alcoholism.
EROs were recorded during a monetary gambling task (MGT) in 12–25 years old participants (N = 1821; males = 48%) from high risk alcoholic families (HR, N = 1534) and comparison low risk community families (LR, N = 287) from the Collaborative Study on the Genetics of Alcoholism (COGA). Impulsivity scores and prevalence of externalizing diagnoses were also compared between LR and HR groups.
HR offspring showed lower theta power and decreased current source density (CSD) activity than LR offspring during loss and gain conditions. Younger males had higher theta power than younger females in both groups, while the older HR females showed more theta power than older HR males. Younger subjects showed higher theta power than older subjects in each comparison. Differences in topography (i.e., frontalization) between groups were also observed. Further, HR subjects across gender had higher impulsivity scores and increased prevalence of externalizing disorders compared to LR subjects.
As theta power during reward processing is found to be lower not only in alcoholics, but also in HR subjects, it is proposed that reduced reward-related theta power, in addition to impulsivity and externalizing features, may be related in a predisposition to develop alcoholism and related disorders.
PMCID: PMC4651365  PMID: 26580209
6.  Genetic Influences on Alcohol Use across Stages of Development: GABRA2 and Longitudinal Trajectories of Drunkenness from Adolescence to Young Adulthood 
Addiction biology  2013;19(6):1055-1064.
Longitudinal analyses allow us to understand how genetic risk unfolds across development, in a way that is not possible with cross-sectional analyses of individuals at different ages. This has received little attention in genetic association analyses. In this study, we test for genetic effects of GABRA2, a gene previously associated with alcohol dependence, on trajectories of drunkenness from age 14 to 25. We use data from 1070 individuals who participated in the prospective sample of the Collaborative Study on the Genetics of Alcoholism (COGA), in order to better understand the unfolding of genetic risk across development. Piecewise linear growth models were fit to model the influence of genotype on rate of increase in drunkenness from early adolescence to young adulthood (14–18 years), the change in drunkenness during the transition to adulthood (18–19 years), and the rate of change in drunkenness across young adulthood (≥ 19 years). Variation in GABRA2 was associated with an increase in drunkenness that occurred at the transition between adolescence and adulthood. The genotypic effect was more pronounced in females. These analyses illustrate the importance of longitudinal data to characterize how genetic effects unfold across development. The findings suggest that transitions across important developmental periods may alter the relative importance of genetic effects on patterns of alcohol use. The findings also suggest the importance of considering gender when evaluating genetic effects on drinking patterns in males and females.
PMCID: PMC3783626  PMID: 23692184
alcohol; COGA; GABRA2; genetic association; longitudinal; trajectories
7.  A Comparison of Three Vulnerability Models for the Onset of Substance Use in a High-Risk Sample* 
The purpose of this prospective study was to compare the following three vulnerability models for early-onset substance use in a high-risk sample: the deviance proneness model, the negative affect regulation model, and a comprehensive model including both delinquency and negative affect.
The sample included 249 15- to 19-year-old adolescents (57% children of alcoholics) and their fathers, all of whom were seen at follow-up 5 years later. At both times of measurement. participants completed a clinical psychiatric interview and a battery of self-report questionnaires assessing temperament, negative affect, delinquency, and substance use.
Although all Of the models fit the data well. the deviance proneness model was parsimonious and provided the best fit. Delinquency played a significant mediating role. whereas negative affect did not. Moreover, negative affect and delinquency were not significantly related to one another.
Results from this study suggest that the deviance proneness model may be a more useful theoretical framework than the negative affect regulation model or a comprehensive model when examining the onset of substance use, particularly in a high-risk sample.
PMCID: PMC2705180  PMID: 18080067
8.  An ADH1B variant and peer drinking in progression to adolescent drinking milestones: Evidence of a gene-by-environment interaction 
Adolescent drinking is an important public health concern, one that is influenced by both genetic and environmental factors. The functional variant rs1229984 in alcohol dehydrogenase 1B (ADH1B) has been associated at a genome-wide level with alcohol use disorders in diverse adult populations. However, few data are available regarding whether this variant influences early drinking behaviors and whether social context moderates this effect. This study examines the interplay between rs1229984 and peer drinking in the development of adolescent drinking milestones.
1,550 European and African American individuals who had a full drink of alcohol before age 18 were selected from a longitudinal study of youth as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Cox proportional hazards regression, with GxE product terms in the final models, was used to study two primary outcomes during adolescence: age of first intoxication and age of first DSM-5 alcohol use disorder symptom.
The minor A allele of rs1229984 was associated with a protective effect for first intoxication (HR=0.56, 95% CI 0.41–0.76) and first DSM-5 symptom (HR=0.45, 95% CI 0.26–0.77) in the final models. Reporting that most or all best friends drink was associated with a hazardous effect for first intoxication (HR=1.81, 95% CI 1.62–2.01) and first DSM-5 symptom (HR=2.17, 95% 1.88–2.50) in the final models. Furthermore, there was a significant GxE interaction for first intoxication (p=.002) and first DSM-5 symptom (p=.01). Among individuals reporting none or few best friends drinking, the ADH1B variant had a protective effect for adolescent drinking milestones, but for those reporting most or all best friends drinking, this effect was greatly reduced.
Our results suggest that the risk factor of best friends drinking attenuates the protective effect of a well-established ADH1B variant for two adolescent drinking behaviors. These findings illustrate the interplay between genetic and environmental factors in the development of drinking milestones during adolescence.
PMCID: PMC4256939  PMID: 25257461
Gene-Environment Interaction; Adolescent; Alcohol Dehydrogenase; Peer drinking
9.  Multiple distinct CHRNB3-CHRNA6 variants are genetic risk factors for nicotine dependence in African Americans and European Americans 
Addiction (Abingdon, England)  2014;109(5):814-822.
Studies have shown association between common variants in the α6–β3 nicotinic receptor subunit gene cluster and nicotine dependence in European Ancestry populations. We investigate whether this generalizes to African Americans, whether the association is specific to nicotine dependence, and whether this region contains additional genetic contributors to nicotine dependence.
We examined consistency of association across studies and race between the α6β3 nicotinic receptor subunit locus and nicotine, alcohol, marijuana, and cocaine dependence in three independent studies.
United States of America
European Americans and African Americans from three case control studies of substance dependence.
Subjects were evaluated using the Semi-Structured Assessment for the Genetics of Alcoholism. Nicotine dependence was determined using the Fagerström Test for Nicotine Dependence.
rs13273442 was significantly associated to nicotine dependence across all three studies in both ancestry groups (OR=0.75, p=5.8 × 10−4 European Americans; OR=0.80, p=0.05 African Americans). No other substance dependence was consistently associated to this variant in either group. Another SNP in the region, rs4952, remains modestly associated with nicotine dependence in the combined data after conditioning on rs13273442.
The common variant rs13273442 in the CHRNB3-CHNRA6 region is significantly associated to nicotine dependence in European Americans and African Americans across studies recruited for nicotine, alcohol, and cocaine dependence. Although these data are modestly powered for other substances, our results provide no evidence that correlates of rs13273442 represent a general substance dependence liability. Additional variants likely account for some of the association of this region to nicotine dependence.
PMCID: PMC3984604  PMID: 24401102
10.  Parent and Child Psychopathology and Suicide Attempts among Children of Parents with Alcohol Use Disorder 
Parents with psychopathology such as alcohol use disorder (AUD) that confers risk for suicide attempt (SA) may have children who are more likely to develop such psychopathology and to attempt suicide, suggesting that risk may be “transmitted” from parents to children. We examined this phenomenon during the transition from childhood to adolescence, when risk for SA increases dramatically. A cohort of 418 children were examined at average age 9.4 (range 7–14) years at enrollment (Time 1, childhood) and approximately five years later, prior to reaching age 18 (Time 2, adolescence). One or both biological parents, oversampled for AUD, were also interviewed. Structural equation models (SEM) examined father-child, mother-child, and either/both parent-child associations. The primary outcome was SA over follow-up among offspring, assessed at Time 2. As hypothesized, parental antisocial personality disorder predicted conduct disorder symptoms in offspring both during childhood and adolescence (parent-child model, father-child model) and maternal AUD predicted conduct disorder symptoms during childhood (mother-child model). However, we did not find evidence to support transmission of depression from parents to offspring either during childhood or adolescence, and parent psychopathology did not show statistically significant associations with SA during adolescence. In conclusion, we conducted a rare study of parent-to-child “transmission” of risk for SA that used a prospective research design, included diagnostic interviews with both parents and offspring, and examined the transition from childhood to adolescence, and the first such study in children of parents with AUD. Results provided mixed support for hypothesized parent-child associations.
PMCID: PMC4059391  PMID: 24716789
adolescent; parent; suicide attempt; alcohol use disorder; risk factor
11.  On the association of common and rare genetic variation influencing body mass index: a combined SNP and CNV analysis 
BMC Genomics  2014;15(1):368.
As the architecture of complex traits incorporates a widening spectrum of genetic variation, analyses integrating common and rare variation are needed. Body mass index (BMI) represents a model trait, since common variation shows robust association but accounts for a fraction of the heritability. A combined analysis of single nucleotide polymorphisms (SNP) and copy number variation (CNV) was performed using 1850 European and 498 African-Americans from the Study of Addiction: Genetics and Environment. Genetic risk sum scores (GRSS) were constructed using 32 BMI-validated SNPs and aggregate-risk methods were compared: count versus weighted and proxy versus imputation.
The weighted SNP-GRSS constructed from imputed probabilities of risk alleles performed best and was highly associated with BMI (p = 4.3×10−16) accounting for 3% of the phenotypic variance. In addition to BMI-validated SNPs, common and rare BMI/obesity-associated CNVs were identified from the literature. Of the 84 CNVs previously reported, only 21-kilobase deletions on 16p12.3 showed evidence for association with BMI (p = 0.003, frequency = 16.9%), with two CNVs nominally associated with class II obesity, 1p36.1 duplications (OR = 3.1, p = 0.009, frequency 1.2%) and 5q13.2 deletions (OR = 1.5, p = 0.048, frequency 7.7%). All other CNVs, individually and in aggregate, were not associated with BMI or obesity. The combined model, including covariates, SNP-GRSS, and 16p12.3 deletion accounted for 11.5% of phenotypic variance in BMI (3.2% from genetic effects). Models significantly predicted obesity classification with maximum discriminative ability for morbid-obesity (p = 3.15×10−18).
Results show that incorporating validated effect sizes and allelic probabilities improve prediction algorithms. Although rare-CNVs did not account for significant phenotypic variation, results provide a framework for integrated analyses.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-368) contains supplementary material, which is available to authorized users.
PMCID: PMC4035084  PMID: 24884913
Body mass index; Obesity; Genome-wide association; Copy number variation; Risk prediction; Polygenic score; FTO; MC4R
12.  Ethnicity and Gender Comparisons of Health Consequences in Adults with Alcohol Dependence 
Substance use & misuse  2013;48(3):200-210.
The moderating effects of ethnicity and gender on factors associated with physical health consequences in adults with alcohol dependence was examined using data from the 2001–2002 U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Black and White respondents with a lifetime diagnosis of DSM-IV alcohol dependence were selected for the study (n = 3,852). A multiple-group structural equation model tested ethnicity, gender, and intervening variables as predictors of physical health status in alcohol dependent men and women. Study findings offer implications for clinical practice with alcohol dependent individuals by identifying likely target groups and problems for intervention.
PMCID: PMC3582739  PMID: 23302062
alcohol; alcohol dependence; physical health; health consequences; gender; ethnicity; race
13.  Copy number variations in 6q14.1 and 5q13.2 are associated with alcohol dependence 
Excessive alcohol use is the third leading cause of preventable death and is highly correlated with alcohol dependence, a heritable phenotype. Many genetic factors for alcohol dependence have been found, but many remain unknown. In search of additional genetic factors, we examined the association between DSM-IV alcohol dependence and all common copy number variations (CNV) with good reliability in the Study of Addiction: Genetics and Environment (SAGE).
All participants in SAGE were interviewed using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA), as a part of three contributing studies. 2,610 non-Hispanic European American samples were genotyped on the Illumina Human 1M array. We performed CNV calling by CNVpartition, PennCNV and QuantiSNP and only CNVs identified by all three software programs were examined. Association was conducted with the CNV (as a deletion/duplication) as well as with probes in the CNV region. Quantitative polymerase chain reaction (qPCR) was used to validate the CNVs in the laboratory.
CNVs in 6q14.1 (P= 1.04 × 10−6) and 5q13.2 (P= 3.37 × 10−4) were significantly associated with alcohol dependence after adjusting multiple tests. On chromosome 5q13.2 there were multiple candidate genes previously associated with various neurological disorders. The region on chromosome 6q14.1 is a gene desert that has been associated with mental retardation, and language delay. The CNV in 5q13.2 was validated whereas only a component of the CNV on 6q14.1 was validated by qPCR. Thus, the CNV on 6q14.1 should be viewed with caution.
This is the first study to show an association between DSM-IV alcohol dependence and CNVs. CNVs in regions previously associated with neurological disorders may be associated with alcohol dependence.
PMCID: PMC3436997  PMID: 22702843
Copy Number Variations; Alcohol dependence; CNV Accuracy
14.  The aggregate effect of dopamine genes on dependence symptoms among cocaine users: Cross-validation of a candidate system scoring approach 
Behavior genetics  2012;42(4):626-635.
Genome-wide studies of psychiatric conditions frequently fail to explain a substantial proportion of variance, and replication of individual SNP effects is rare. We demonstrate a selective scoring approach, in which variants from several genes known to directly affect the dopamine system are considered concurrently to explain individual differences in cocaine dependence symptoms. 273 SNPs from eight dopamine-related genes were tested for association with cocaine dependence symptoms in an initial training sample. We identified a four-SNP score that accounted for 0.55% of the variance in a separate testing sample (p = 0.037). These findings suggest that 1) limiting investigated SNPs to those located in genes of theoretical importance improves the chances of identifying replicable effects by reducing statistical penalties for multiple testing, and 2) considering top-associated SNPs in the aggregate can reveal replicable effects that are too small to be identified at the level of individual SNPs.
PMCID: PMC3416038  PMID: 22358648
candidate gene; cocaine dependence; dopamine
Many states require screening of individuals arrested for driving under the influence of alcohol (DUI) to determine recidivism risk and the need for treatment based on severity of alcohol problems. Several screening instruments use DSM-IV criteria for alcohol abuse and dependence to assess alcohol problems in this population, but whether they adequately measure alcohol problems in individuals with DUIs has not been examined. In addition, gender differences in DUI samples suggest that female offenders have more severe alcohol problems than male offenders. The current study examines differences in alcohol criteria functioning by DUI history and gender using an item response theory (IRT) approach.
Data from diagnostic interviews with 8605 participants in the Collaborative Study on the Genetics of Alcoholism, including 1655 who ever reported a DUI arrest (20% women), were used to examine differences in alcohol criteria functioning between men and women with and without DUIs. The factor underlying item response was conceptualized as unidimensional, representing alcohol problem severity.
Social/interpersonal problems, larger/longer, and inability/persistent desire to quit displayed greater discrimination of IRT-defined alcohol problem severity among individuals with DUIs than those without. Irrespective of DUI status, women had a higher threshold than men for time spent drinking or recovering. Women without DUIs had a higher threshold than similar men for social/interpersonal problems. Taken as a whole, the criteria yielded similar amounts of information in all groups.
DSM-IV criteria for alcohol abuse and dependence adequately detect alcohol problem severity in individuals with DUIs and some are better at detecting severity in this particularly high-risk group than in individuals without DUIs. However, the criteria as a whole are equally effective in measuring alcohol problem severity among individuals with and without DUIs, and may be used with confidence in screening DUI offenders.
PMCID: PMC3166544  PMID: 21631541
DUI; Alcohol Use Disorder; Item Response Theory
16.  Copy Number Variation Accuracy in Genome-Wide Association Studies 
Human Heredity  2011;71(3):141-147.
Copy number variations (CNVs) are a major source of alterations among individuals and are a potential risk factor in many diseases. Numerous diseases have been linked to deletions and duplications of these chromosomal segments. Data from genome-wide association studies and other microarrays may be used to identify CNVs by several different computer programs, but the reliability of the results has been questioned.
To help researchers reduce the number of false-positive CNVs that need to be followed up with laboratory testing, we evaluated the relative performance of CNVPartition, PennCNV and QuantiSNP, and developed a statistical method for estimating sensitivity and positive predictive values of CNV calls and tested it on 96 duplicate samples in our dataset.
We found that the positive predictive rate increases with the number of probes in the CNV and the size of the CNV, with the highest positive predicted rates in CNVs of at least 500 kb and at least 100 probes. Our analysis also indicates that identifying CNVs reported by multiple programs can greatly improve the reproducibility rate and the positive predicted rate.
Our methods can be used by investigators to identify CNVs in genome-wide data with greater reliability.
PMCID: PMC3153341  PMID: 21778733
Accuracy; Copy number variations; False positives; Genome-wide association studies
17.  Predicting sensation seeking from dopamine genes: A candidate system approach 
Psychological science  2010;21(9):1282-1290.
Sensation seeking is a heritable personality trait that has been reliably linked to behavior disorders. The dopamine system has been hypothesized to contribute to individual differences in sensation seeking, and both experimental and observational studies in humans and non-human animals provide evidence for this relationship. We present here a candidate-system approach to genetic association analysis of sensation seeking, in which single nucleotide polymorphisms (SNPs) from a number of dopaminergic genes were analyzed. Using 273 SNPs from eight dopamine genes in a sample of 635 unrelated individuals, we examined the aggregate effects of those SNPs significantly associated with sensation seeking. Multiple SNPs in four dopamine genes accounted for significant variance in sensation seeking. These results suggest that aggregation of multiple SNPs within genes relevant to a specific neurobiological system into a “genetic risk score” may explain a nontrivial proportion of variance in human traits.
PMCID: PMC3031097  PMID: 20732903
sensation seeking; dopamine; candidate gene; association study
18.  P300 and the Stroop Effect in Overweight Minority Adolescents 
Neuropsychobiology  2010;61(4):180-187.
The goal was to examine the relationship between a risk factor for poor cognitive control and a health outcome of growing public significance – an excess body mass – among adolescents.
To this end, 109 adolescents aged 14–20 years were recruited and assigned to 1 of 4 groups defined by the crossing of the absence versus presence of a parental history (PH) of externalizing disorders with a body mass index (BMI) percentile (BMIP) <85 versus ≥85. The principal measure estimating cognitive control was the P300 event-related electroencephalographic response recorded during the Stroop task.
The analyses revealed a synergistic interaction between BMIP rank, PH and trial type: the increase in P300 latency and the decrease in response accuracy, elicited by the presence of interfering information, were markedly greater in high-BMIP subjects with a PH of externalizing disorders than in the other subject groups. Analyses of a later component, the N450, previously associated with the Stroop interference effect, revealed no effect of BMI or PH.
We conclude that subjects with both a PH of externalizing disorders and an excess BMI constitute a unique group that is less able to resolve cognitive conflict than others. The excessive delay in P300 evoked by conflicting response demands in these subjects may be a marker of a heritable factor that increases risk for both excess body mass and substance use disorders.
PMCID: PMC2865490  PMID: 20299812
P300; Evoked potentials; Overweight; Family history; Externalizing disorders; Obesity; Adolescents; Stroop effect
19.  Alcohol criteria endorsement and psychiatric and drug use disorders among DUI offenders: Greater severity among women and multiple offenders 
Addictive behaviors  2008;34(5):432-439.
Data from the Collaborative Study on the Genetics of Alcoholism (COGA), a high-risk family study of alcohol dependence, were used to examine differences in alcohol diagnostic criteria endorsement and psychiatric and drug use disorders by gender and by number of DUI offenses.
Individuals with two or more DUIs exhibited greater severity of alcohol dependence than those with none or one DUI. This severity was characterized in three ways: (1) higher endorsement of alcohol diagnostic criterion items, with evidence of greater severity among women, (2) higher prevalence of co-occurring lifetime psychiatric disorders, and (3) higher rates of drug use and of dependence on cocaine, stimulants, and, for women only, marijuana and opiates.
By examining gradations of disorder within a combination of two high-risk indicators, DUI and family vulnerability, this study provides useful information for clinical research about individuals with chronic and severe alcohol problems. In addition, the observed gender differences in this high-risk sample will contribute to the literature on alcohol dependence among women at the more severe end of the dependence spectrum.
PMCID: PMC2855219  PMID: 19167170
Driving under the influence; Alcoholism; Drug dependency; Mental disorders
20.  Do Personality Characteristics and Risk Taking Mediate the Relationship Between Paternal Substance Dependence and Adolescent Substance Use? 
Addictive behaviors  2006;32(9):1852-1862.
This longitudinal study examined whether adolescent personality characteristics and risk taking mediate the relationship between paternal substance dependence and adolescent substance use. At Time 1, the sample included 249 15–19 year-old adolescents and their fathers. These individuals also were assessed five years later (Time 2). Results indicated that paternal substance dependence directly and indirectly (via personality and risk taking) predicted adolescent substance use. Paternal substance dependence had significant direct effects on age when the adolescent first used marijuana and significant indirect effects on age when regular drinking began, age when first used marijuana, and frequency of drinking to get “high” or “drunk.” All of the indirect personality effects were via adolescent disinhibition. In addition, adolescent risk taking further mediated personality and adolescent substance use. Results from this study are discussed in relation to an epigenetic perspective of human development.
PMCID: PMC1993011  PMID: 17241748
adolescence; alcohol; drug; risk taking; personality; COAs
21.  Paternal Alcoholism and Youth Substance Abuse: The Indirect Effects of Negative Affect, Conduct Problems, and Risk Taking 
This longitudinal study followed 200 adolescents into early adulthood to explore the potential mediating roles that hostility, sadness, conduct problems, and risk taking play in the relationship between paternal alcoholism and substance abuse. Results indicated that paternal alcoholism predicted hostility; in turn, hostility predicted risk taking, which predicted substance abuse.
PMCID: PMC2235815  PMID: 18207099

Results 1-21 (21)