Trauma exposure, alcohol consumption, and sleep quality: a latent growth curve model.

This study examined the relations among precollege trauma exposure, alcohol use upon entering college, growth in alcohol use, and sleep quality in a sample of undergraduate students. Participants were 932 students from a large, urban, public university. Participants completed a survey upon entering college and then subsequent follow-up surveys each Spring semester. Precollege trauma exposure was associated with both baseline and growth in alcohol use, whereby higher levels of trauma were associated with higher baseline alcohol use, but with less steep increases in growth rate, as compared to those with lower levels of trauma. Baseline alcohol use was associated with sleep quality whereby those with higher levels of consumption demonstrated worsened sleep quality. This study provides longitudinal evidence for the relations among trauma, alcohol use, and sleep quality. Although the relationship between trauma and alcohol is well-established, further work is needed to identify how this relationship impacts additional health outcomes.

An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry.

Fast beta (20-28 Hz) electroencephalogram (EEG) oscillatory activity may be a useful endophenotype for studying the genetics of disorders characterized by neural hyperexcitability, including substance use disorders (SUDs). However, the genetic underpinnings of fast beta EEG have not previously been studied in a population of African-American ancestry (AA). In a sample of 2382 AA individuals from 482 families drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a genome-wide association study (GWAS) on resting-state fast beta EEG power. To further characterize our genetic findings, we examined the functional and clinical/behavioral significance of GWAS variants. Ten correlated single-nucleotide polymorphisms (SNPs) (r2>0.9) located in an intergenic region on chromosome 3q26 were associated with fast beta EEG power at P<5 × 10-8. The most significantly associated SNP, rs11720469 (ß: -0.124; P<4.5 × 10-9), is also an expression quantitative trait locus for BCHE (butyrylcholinesterase), expressed in thalamus tissue. Four of the genome-wide SNPs were also associated with Diagnostic and Statistical Manual of Mental Disorders Alcohol Dependence in COGA AA families, and two (rs13093097, rs7428372) were replicated in an independent AA sample (Gelernter et al.). Analyses in the AA adolescent/young adult (offspring from COGA families) subsample indicated association of rs11720469 with heavy episodic drinking (frequency of consuming 5+ drinks within 24 h). Converging findings presented in this study provide support for the role of genetic variants within 3q26 in neural and behavioral disinhibition. These novel genetic findings highlight the importance of including AA populations in genetics research on SUDs and the utility of the endophenotype approach in enhancing our understanding of mechanisms underlying addiction susceptibility.

Prevalence and predictors of sexual assault among a college sample.

OBJECTIVE: This study examined the prevalence and correlates of precollege, college-onset, and repeat sexual assault (SA) within a representative student sample. PARTICIPANTS: A representative sample of 7,603 students. METHODS: Incoming first-year students completed a survey about their exposure to broad SA prior to college, prior trauma, personality, relationships, and mental health. Broad SA was then reassessed each spring semester while enrolled. RESULTS: Nearly 20% of the sample reported experiencing broad SA, with women endorsing significantly higher rates compared with males. Prior victimization before coming to college was related to a greater risk of victimization in college, and there was no statistically significant difference between males and females who reported revictimization. Correlates of college-onset broad SA were found and are discussed. CONCLUSIONS: Given the need for SA intervention and prevention on college campuses, identification of factors potentially contributing to exposure within this population is essential.

Genome-wide association data suggest ABCB1 and immune-related gene sets may be involved in adult antisocial behavior.

Adult antisocial behavior (AAB) is moderately heritable, relatively common and has adverse consequences for individuals and society. We examined the molecular genetic basis of AAB in 1379 participants from a case-control study in which the cases met criteria for alcohol dependence. We also examined whether genes of interest were expressed in human brain. AAB was measured using a count of the number of Antisocial Personality Disorder criteria endorsed under criterion A from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). Participants were genotyped on the Illumina Human 1M BeadChip. In total, all single-nucleotide polymorphisms (SNPs) accounted for 25% of the variance in AAB, although this estimate was not significant (P=0.09). Enrichment tests indicated that more significantly associated genes were over-represented in seven gene sets, and most were immune related. Our most highly associated SNP (rs4728702, P=5.77 × 10(-7)) was located in the protein-coding adenosine triphosphate-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1). In a gene-based test, ABCB1 was genome-wide significant (q=0.03). Expression analyses indicated that ABCB1 was robustly expressed in the brain. ABCB1 has been implicated in substance use, and in post hoc tests we found that variation in ABCB1 was associated with DSM-IV alcohol and cocaine dependence criterion counts. These results suggest that ABCB1 may confer risk across externalizing behaviors, and are consistent with previous suggestions that immune pathways are associated with externalizing behaviors. The results should be tempered by the fact that we did not replicate the associations for ABCB1 or the gene sets in a less-affected independent sample.

Impulsivity and genetic variants in DRD2 and ANKK1 moderate longitudinal associations between sleep problems and overweight from ages 5 to 11.

OBJECTIVE: Short sleep duration and sleep problems increase risks of overweight and weight gain. Few previous studies have examined sleep and weight repeatedly over development. This study examined the associations between yearly reports of sleep problems and weight status from ages 5 to 11. Although, previous studies have shown that inter-individual differences moderate the effect of short sleep duration on weight, it is not known whether inter-individual differences also moderate the effect of sleep problems on weight. We tested how the longitudinal associations between sleep problems and weight status were moderated by impulsivity and genetic variants in DRD2 and ANKK1. DESIGN: Seven-year longitudinal study. PARTICIPANTS: A total of 567 children from the Child Development Project for the analysis with impulsivity and 363 for the analysis with genetic variants. MEASUREMENTS AND RESULTS: Sleep problems and weight status were measured by mothers' reports yearly. Impulsivity was measured by teachers' reports yearly. Six single-nucleotide polymorphisms located in DRD2 and ANKK1 were genotyped. Data were analyzed using multilevel modeling. Higher average levels of sleep deprivation across years were associated with greater increases in overweight (P=0.0024). Sleep problems and overweight were associated at both within-person across time (P<0.0001) and between-person levels (P<0.0001). Impulsivity and two polymorphisms, rs1799978 and rs4245149 in DRD2, moderated the association between sleep problems and overweight; the association was stronger in children who were more impulsive (P=0.0022), in G allele carriers for rs1799978 (P=0.0007) and in A allele carriers for rs4245149 (P=0.0002). CONCLUSIONS: This study provided incremental evidence for the influence of sleep problems on weight. Findings of DRD2, ANKK1 and impulsivity are novel; they suggest that reward sensitivity and self-regulatory abilities might modulate the influences of sleep on weight gain. The analysis of polymorphisms was restricted to European Americans and hence the results might not generalize to other populations.

Common biological networks underlie genetic risk for alcoholism in African- and European-American populations.

Alcohol dependence (AD) is a heritable substance addiction with adverse physical and psychological consequences, representing a major health and economic burden on societies worldwide. Genes thus far implicated via linkage, candidate gene and genome-wide association studies (GWAS) account for only a small fraction of its overall risk, with effects varying across ethnic groups. Here we investigate the genetic architecture of alcoholism and report on the extent to which common, genome-wide SNPs collectively account for risk of AD in two US populations, African-Americans (AAs) and European-Americans (EAs). Analyzing GWAS data for two independent case-control sample sets, we compute polymarker scores that are significantly associated with alcoholism (P = 1.64 × 10(-3) and 2.08 × 10(-4) for EAs and AAs, respectively), reflecting the small individual effects of thousands of variants derived from patterns of allelic architecture that are population specific. Simulations show that disease models based on rare and uncommon causal variants (MAF < 0.05) best fit the observed distribution of polymarker signals. When scoring bins were annotated for gene location and examined for constituent biological networks, gene enrichment is observed for several cellular processes and functions in both EA and AA populations, transcending their underlying allelic differences. Our results reveal key insights into the complex etiology of AD, raising the possibility of an important role for rare and uncommon variants, and identify polygenic mechanisms that encompass a spectrum of disease liability, with some, such as chloride transporters and glycine metabolism genes, displaying subtle, modifying effects that are likely to escape detection in most GWAS designs.

Prospective relationships of ADHD symptoms with developing substance use in a population-derived sample.

BACKGROUND: Clinically ascertained reports suggest that boys and girls with attention deficit hyperactivity disorder (ADHD) may differ from each other in their vulnerability to substance use problems. METHOD: A total of 1545 Finnish adolescents were assessed for DSM-IV-based ADHD symptoms by their parents and classroom teachers using standardized rating scales at age 11-12 years. At age 14, substance use disorders and psychiatric co-morbidity were assessed with the Semi-Structured Assessment for the Genetics of Alcoholism, providing DSM-III-R/DSM-IV diagnoses for Axis I disorders. At age 17.5, substance use was assessed by multi-item questionnaire. RESULTS: Although baseline ADHD symptoms were less common among females, they were more predictive of adverse substance use outcomes once conduct disorder and previous substance use were controlled for. Only in females were baseline ADHD symptoms significant predictors of alcohol abuse and dependence and illicit drug use at age 14. At the age of 17.5, parents' reports of inattentiveness and hyperactivity were significant predictors for frequent alcohol use in both sexes, but they were more predictive of frequent alcohol and illicit drug use in girls. Impulsivity in teachers' ratings predicted frequent alcohol use and illicit drug use in boys. Parental reports of inattentiveness in their 11-/12-year-old daughters were a consistent predictor for illicit drug use across adolescence. CONCLUSIONS: Inattentiveness and hyperactivity may be more predictive of alcohol use disorders and maladaptive patterns of alcohol and illicit drug use among girls than boys. The importance of these behavioural symptoms should be assessed further in the community, as they could jeopardize adolescents' successful transitioning into adult roles.

DRD2 and DRD4 in relation to regular alcohol and cannabis use among adolescents: does parenting modify the impact of genetic vulnerability? The TRAILS study.

AIMS: The aims of the present study were to determine the direct effect of DRD2 and DRD4, as well as their interaction with parenting (i.e. rejection, overprotection and emotional warmth), on the development of regular alcohol and cannabis use in 1192 Dutch adolescents from the general population. METHODS: Information was obtained by self-report questionnaires. Perceived rejection, overprotection and emotional warmth were assessed at age 10-12. Regular alcohol and cannabis use were determined at age 15-18 and defined as the consumption of alcohol on 10 or more occasions in the past four weeks, and the use of cannabis on 4 or more occasions in the past four weeks. Models were adjusted for age, sex, parental alcohol or cannabis use, and externalizing behavior. RESULTS: Carrying the A1 allele of the DRD2 TaqIA polymorphism, or the 7 repeat DRD4, was not directly related to regular alcohol or cannabis use. In addition, adolescent carriers of these genetic risk markers were not more susceptible to the influence of less optimal parenting. Main effects for parenting indicated that overprotection increased the risk of regular alcohol use, whereas the risk of cannabis use was enhanced by parental rejection and buffered by emotional warmth. CONCLUSIONS: Our findings do not support an association between DRD2/DRD4 and regular alcohol and cannabis use in adolescents. Given the substance-specific influences of rejection, overprotection and emotional warmth, these parenting factors might be promising candidates for prevention work.

Genome-wide association study of conduct disorder symptomatology.

Conduct disorder (CD) is one of the most prevalent childhood psychiatric conditions, and is associated with a number of serious concomitant and future problems. CD symptomatology is known to have a considerable genetic component, with heritability estimates in the range of 50%. Despite this, there is a relative paucity of studies aimed at identifying genes involved in the susceptibility to CD. In this study, we report results from a genome-wide association study of CD symptoms. CD symptoms were retrospectively reported by a psychiatric interview among a sample of cases and controls, in which cases met the criteria for alcohol dependence. Our primary phenotype was the natural log transformation of the number of CD symptoms that were endorsed, with data available for 3963 individuals who were genotyped on the Illumina Human 1M beadchip array. Secondary analyses are presented for case versus control status, in which caseness was established as endorsing three or more CD symptoms (N = 872 with CD and N = 3091 without CD). We find four markers that meet the criteria for genome-wide significance (P<5 × 10(-8)) with the CD symptom count, two of which are located in the gene C1QTNF7 (C1q and tumor necrosis factor-related protein 7). There were six additional SNPs in the gene that yielded converging evidence of association. These data provide the first evidence of a specific gene that is associated with CD symptomatology. None of the top signals resided in traditional candidate genes, underscoring the importance of a genome-wide approach for identifying novel variants involved in this serious childhood disorder.

Genetic origins of the association between verbal ability and alcohol dependence symptoms in young adulthood.

BACKGROUND: Cognitive deficits in alcohol dependence (AD) have been observed, poorer verbal ability being among the most consistent findings. Genetic factors influence both cognitive ability and AD, but whether these influences overlap is not known. METHOD: A subset of 602 monozygotic (MZ) and dizygotic (DZ) twins from FinnTwin16, a population-based study of Finnish twins, was used to study the associations of verbal ability with DSM-III-R diagnosis and symptoms of AD, the maximum number of drinks consumed in a 24-h period, and the Rutgers Alcohol Problem Index (RAPI) scores. These twins, most of them selected for within-pair discordance or concordance for their RAPI scores at age 18.5 years, were studied with neuropsychological tests and interviewed with the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) in young adulthood (mean age 26.2 years, range 23-30 years). RESULTS: All alcohol problem measures were associated with lower scores on the Vocabulary subtest of the Wechsler Adult Intelligence Scale - Revised (WAIS-R), a measure of verbal ability. In bivariate genetic models, Vocabulary and the alcohol problem measures had moderate heritabilities (0.54-0.72), and their covariation could be explained by correlated genetic influences (genetic correlations -0.20 to -0.31). CONCLUSIONS: Poorer verbal ability and AD have partly overlapping biological etiology. The genetic and environmental influences on the development of cognitive abilities, alcohol problems and risk factors for AD should be studied further with prospective longitudinal designs.

Predicting alcohol consumption in adolescence from alcohol-specific and general externalizing genetic risk factors, key environmental exposures and their interaction.

BACKGROUND: Alcohol consumption is influenced by specific genetic risk factors for alcohol use disorders (AUDs), non-specific genetic risk factors for externalizing behaviors and various environmental experiences. We have limited knowledge of how these risk factors inter-relate through development. METHOD: Retrospective assessments in 1796 adult male twins using a life history calendar of key environmental exposures and alcohol consumption from early adolescence to mid-adulthood. Analysis by linear mixed models. RESULTS: The importance of non-specific genetic risk factors on maximal alcohol consumption rose rapidly in early to mid-adolescence, peaked at ages 15-17 years and then declined slowly. Alcohol-specific genetic risk factors increased slowly in influence through mid-adulthood. We detected robust evidence for environmental moderation of genetic effects on alcohol consumption that was more pronounced in early and mid-adolescence than in later periods. Alcohol availability, peer deviance and low prosocial behaviors showing the strongest moderation effects. More interactions with environmental risk factors were seen for the non-specific externalizing disorder risk than for specific genetic risk for AUDs. CONCLUSIONS: The impact of specific and non-specific genetic influences on alcohol consumption have different development trajectories. Genetic effects on alcohol use are more pronounced when social constraints are minimized (e.g. low prosocial behaviors or parental monitoring) or when the environment permits easy access to alcohol and/or encourages its use (e.g. high alcohol availability or peer deviance). Gene-environment interactions influencing alcohol intake may be more robust at younger ages, indicating greater plasticity of genetic influences early in the development of drinking patterns.

Chernobyl exposure as stressor during pregnancy and behaviour in adolescent offspring.

OBJECTIVE: Research in animals has shown that exposure to stressors during pregnancy is associated with offspring behavioural disorders. We aimed to study the effect of in utero exposure to the Chernobyl disaster in 1986, and maternal anxiety presumably associated with that exposure, on behaviour disorder observed at age 14. METHOD: Exposed (n = 232) and non-exposed Finnish twins (n = 572) were compared. A semi-structured interview was used to assess lifetime symptoms of depression, generalized anxiety disorder, attention deficit hyperactivity disorder, conduct disorder and oppositional defiant disorder symptoms. RESULTS: Adolescents who were exposed from the second trimester in pregnancy onwards, had a 2.32-fold risk (95% CI: 1.13-4.72) of having lifetime depression symptoms, an increased risk of fulfilling DSM-III-R criteria of a major depressive disorder (OR = 2.48, 95% CI: 1.06-5.7), and a 2.01-fold risk (95% CI: 1.14-3.52) of having attention deficit hyperactivity disorder symptoms. CONCLUSION: Perturbations in fetal brain development during the second trimester may be associated with the increased prevalence of depressive and attention deficit hyperactivity disorder symptoms.

A genome-wide screen for genes influencing conduct disorder.

While behavioral genetic studies have suggested that childhood conduct disorder is under genetic influence, studies aimed at gene identification are lacking. This study represents the first genome-wide linkage analysis directed toward identifying genes contributing to conduct disorder. Genome screens of retrospectively reported childhood conduct disorder and conduct disorder symptomatology were carried out in the genetically informative adult sample collected as part of the Collaborative Study on the Genetics of Alcoholism (COGA). The results suggest that regions on chromosomes 19 and 2 may contain genes conferring risk to conduct disorder. Interestingly, the same region on chromosome 2 has also been linked to alcohol dependence in this sample. Childhood conduct disorder is known to be associated with the susceptibility for future alcohol problems. Taken together, these findings suggest that some of the genes contributing to alcohol dependence in adulthood may also contribute to conduct disorder in childhood.

Exploring gene-environment interactions: socioregional moderation of alcohol use.

Examples of gene-environment interaction in human behavioral data are relatively rare; those that exist have used simple, dichotomous measures of the environment. The authors describe a model that allows for the specification of more continuous, more realistic variations in environments as moderators of genetic and environmental influences on behavior. Using data from a population-based Finnish twin study, the authors document strong moderating effects of socioregional environments on genetic and environmental influences on adolescent alcohol use, with nearly a five-fold difference in the magnitude of genetic effects between environmental extremes. The incorporation of specific environmental measures into genetically informative designs should prove to be a powerful method for better understanding the nature of gene-environment interaction and its contribution to the etiology of behavioral variation.

Drinking or abstaining at age 14? A genetic epidemiological study.

BACKGROUND: Regular drinking by age 14 years is a significant risk factor for alcoholism, and genetically informative data suggest that whether a young adolescent abstains or drinks is largely attributable to familial (or other shared) environmental factors. METHODS: Three consecutive birth cohorts of Finnish twins, enrolled into a longitudinal study at age 11 to 12 years, completed a follow-up questionnaire within 3 months of their 14th birthdays. The sample included 1380 twin sisters and 1330 twin brothers at age 14, and at that age, 35.4% reported using alcohol. Genetic analyses (model-fitting of twin pair data) and epidemiological analyses (logistical regressions of data from individual twins) were conducted to examine predictive factors of drinking versus abstinence at age 14. RESULTS: Polychoric correlations were substantial across all same-sex twin pairs but were lower for brother-sister twins, suggesting significant influences of common environments, with some sex-specific effects. Common environmental effects were equivalent in male and female adolescents and accounted for 76% of the total variation in abstinence/drinking. Logistical regression analyses among 2206 individual twins with complete data on risk-relevant measures at both baseline and follow-up identified significant predictors of drinking or abstaining at age 14, including female sex, twin sibling of the opposite sex, accelerated pubertal development, and the twins' assessments, made at age 12, of reduced parental monitoring and a less supportive home atmosphere; drinking at age 14 was also predicted by behaviors rated by the twins' classroom teachers 2 years earlier, increasing with rated behavioral problems but decreasing with rated emotional problems. CONCLUSIONS: Our results show that environmental factors shared by twin siblings account for most of the variance in abstaining or drinking at age 14. We identify predictors of drinking in the adolescent twins' home environments and in their dispositional behaviors, sibling interactions, and pubertal timing.

Gene-environment interaction in patterns of adolescent drinking: regional residency moderates longitudinal influences on alcohol use.

BACKGROUND: Drinking frequency escalates rapidly during adolescence. Abstinence declines markedly, and drinking monthly or more often becomes normative. Individual differences in adolescent drinking patterns are large, and some patterns are predictive of subsequent drinking problems; little, however, is known of the gene-environment interactions that create them. METHODS: Five consecutive and complete birth cohorts of Finnish twins, born 1975-1979, were enrolled sequentially into a longitudinal study and assessed, with postal questionnaires, at ages 16, 17, and 18.5 years. The sample included 1786 same-sex twin pairs, of whom 1240 pairs were concordantly drinking at age 16. Maximum likelihood models were fit in longitudinal analyses of the three waves of drinking data to assess changes in genetic and environmental influences on alcohol use across adolescence. Secondary analyses contrasted twin pairs residing in rural versus those in urban environments to investigate gene-environment interactions. RESULTS: Longitudinal analyses revealed that genetic factors influencing drinking patterns increased in importance across the 30-month period, and effects arising from common environmental influences declined. Distributions of drinking frequencies in twins residing in urban and rural environments were highly similar, but influences on drinking varied between the two environments. Genetic factors assumed a larger role among adolescents residing in urban areas, while common environmental influences were more important in rural settings. Formal modeling of the data established a significant gene-environment interaction. CONCLUSIONS: The results document the changing impact of genetic and environmental influences on alcohol use across adolescence. Importantly, the results also reveal a significant gene-environment interaction in patterns of adolescent drinking and invite more detailed analyses of the pathways and mechanisms by which environments modulate genetic effects.

Pubertal timing and substance use: associations between and within families across late adolescence.

In the present study, between-family analyses of data from adolescent twin girls offer new evidence that early menarche is associated with earlier initiation and greater frequency of smoking and drinking. The role of personality factors and peer relationships in that association was investigated, and little support was found for their involvement. Novel within-family analyses replicating associations of substance use with pubertal timing in contrasts of twin sisters selected for extreme discordance for age at menarche are reported. Within-family replications demonstrated that the association of pubertal timing with substance use cannot be explained solely by between-family confounds. Within-family analyses demonstrated contextual modulation of the influence of pubertal timing: Its impact on drinking frequency is apparent only among girls in urban settings. Sibling comparisons illustrate a promising analytic tool for studying diverse developmental outcomes.

Testing between-family associations in within-family comparisons.

Using behaviorally discordant siblings to test for gene-behavior associations is a common tool in molecular genetics, because the within-family contrast offers a research design that avoids confounds inevitable in all between-family comparisons of unrelated individuals. We propose a similar strategy to assess the behavior-behavior associations on which much of psychological science is built. Between-family correlations of personality test scores (e.g., sensation seeking) and behavioral outcomes (e.g., substance use) may be mediated by variables that differ between families (e.g., social class or religiosity) and correlate with both personality and outcome. Contrasting twin and nontwin siblings who were highly discordant for behavioral correlates of substance use, we tested whether between-family behavioral correlations replicated within families. Some, but not all, did. Within-family analyses of behaviorally discordant siblings may find wide application in efforts to clarify the meaning of correlational research data.

The reduction of stereotypic screaming in a severely retarded boy through a visual screening procedure.

The stereotypic screaming of a 4.2 yr old severely retarded boy was successfully reduced with a visual screening procedure in both school and home settings. Treatment gains were maintained over time and there was some evidence of treatment generalizing across time and persons. Social validation ratings confirmed the effectiveness of the program.