The Role of Socioregional Factors in Moderating Genetic Influences on Early Adolescent Behavior Problems and Alcohol Use

Background: Twin and family studies have demonstrated that adolescent alcohol use and behavior problems are influenced by a combination of genetic and environmental factors. More recently, studies have begun to investigate how genetic and environmental influences may interact, with efforts underway to identify specific environmental variables that moderate the expression of genetic predispositions. Previously, we have reported that community‐level factors, including urban/rural residency, migration rates, and prevalence of young adults, moderate the importance of genetic effects on alcohol use in late adolescence (ages 16 to 18). Here, we extend these findings to test for moderating effects of these socioregional factors on alcohol use and behavior problems assessed in a younger sample of adolescent Finnish twins. Methods: Using data from the population‐based Finnish twin study, FinnTwin12, biometric twin models were fit to data on >1,400 twin pairs to examine the significance of each of the socioregional moderating variables on alcohol use measured at age 14, and behavior problems, measured at age 12. Results: We find no evidence of a moderating role of these socioregional variables on alcohol use; however, there was significant moderation of genetic influences on behavior problems, with effects limited to girls. Genetic influences assumed greater importance in urban settings, communities with greater migration, and communities with a higher percentage of slightly older adolescents. Conclusions: The moderation effects observed on behavior problems in early adolescence paralleled the effects found on alcohol use late in adolescence in an independent sample, providing further support for the idea that behavior problems may represent an earlier manifestation of the predisposition to subsequent alcohol problems. Our findings also support the growing body of evidence suggesting that females may be more susceptible to a variety of environmental influences than males.     

Stress, Depression, Irrational Beliefs, and Alcohol Use and Problems in a College Student Sample

One-hundred thirty-five alcohol-using college students completed a questionnaire on their levels of alcohol use, moderate-to-severe problems with alcohol use, the Eysenck 1.7 measure of impulsiveness and venturesomeness, the Zung depression scale, the "Hassles and Uplifts" scale of life stresses, and a scale of proneness to irrational beliefs. Impulsivity and venturesomeness were significantly correlated with quantity-frequency of alcohol use, but not with the occurrence of alcohol use problems; whereas depression, stress, and irrational beliefs were significantly correlated with alcohol problems, but not with alcohol use. Multiple regression analyses indicated that the effect of stress on alcohol problems was mediated by depression, whereas the effect of depression, in turn, was mediated by irrational beliefs.     

Common Genetic Contributions to Alcohol and Cannabis Use and Dependence Symptomatology

Background: Despite mounting evidence that use of and dependence on alcohol and cannabis are influenced by heritable factors, the extent to which heritable influences on these phenotypes overlap across the 2 substances has only rarely been explored. In the current study, we quantified cross‐substance overlap in sources of variance and estimated the degree to which within‐substance associations between use and dependence measures are attributable to common genetic and environmental factors for alcohol and cannabis. Methods: The sample was comprised of 6,257 individuals (2,761 complete twin pairs and 735 singletons) from the Australian Twin Registry, aged 24 to 36 years. Alcohol and cannabis use histories were collected via telephone diagnostic interviews and used to derive an alcohol consumption factor, a frequency measure for cannabis use, and DSM‐IV alcohol and cannabis dependence symptom counts. Standard genetic analyses were conducted to produce a quadrivariate model that provided estimates of overlap in genetic and environmental influences across the 4 phenotypes. Results: Over 60% of variance in alcohol consumption, cannabis use, and cannabis dependence symptoms, and just under 50% of variance in alcohol dependence (AD) symptoms were attributable to genetic sources. Shared environmental factors did not contribute significantly to the 4 phenotypes. Nearly complete overlap in heritable influences was observed for within‐substance measures of use and dependence symptoms. Genetic correlations across substances were 0.68 and 0.62 for use and dependence symptoms, respectively. Conclusions: Common heritable influences were evident for alcohol and cannabis use and for AD and cannabis dependence symptomatology, but findings indicate that substance‐specific influences account for the majority of the genetic variance in the cannabis use and dependence phenotypes. By contrast, the substantial correlations between alcohol use and AD symptoms and between cannabis use and cannabis dependence symptoms suggest that measures of heaviness of use capture much of the same genetic liability to alcohol‐ and cannabis‐related problems as dependence symptomatology.     

Smoking and Intoxication after Alcohol Challenge in Women and Men: Genetic Influences

In an earlier analysis, men and women who were current or former smokers were found to report feeling less intoxicated on average than nonsmokers after ingestion of a challenge dose of alcohol. Here, we examine whether differences in subjective response to alcohol and a tendency to smoke cigarettes are transmitted together in families; and, if so, whether this association might be entirely explained by the same heritable factors that influence alcohol intake (as we might expect if both smoking and subjective intoxication are influenced by some general susceptibility for substance use). Alcohol challenge data on 388 Australian male and female twins (194 complete pairs) were reanalyzed using multivariate genetic analysis to evaluate the association between cigarette smoking and self-report intoxication after a standard dose of alcohol. In women, we could not reject the hypothesis of complete genetic overlap between effects on intoxication rating and history of smoking, and a significant residual genetic correlation between smoking and postalcohol intoxication persisted even when genetic influences on alcohol consumption were controlled for. In men, the familial association seemed to be largely environmentally mediated and associated with differences in drinking history. These findings prompt the question of whether, in some individuals, cigarette smoking may contribute to the development of tolerance to the effects of alcohol.     

Changes in Alcohol Use and Alcohol-Related Problems among 7th to 12th Grade Students in New York State, 1983–1994

Three comparable representative samples of 7th to 12th grade students in New York State were surveyed in 1983, 1990, and 1994 to determine changes in the patterns of alcohol use over the past decade. Each of the three samples was large ( n = 27,335, 23,860, and 19,321, respectively), permitting detailed analysis of changes in alcohol use in various adolescent subgroups according to age, gender, and race/ethnicity. Previous research revealed that there were marked decreases in the prevalence of overall drinking, heavy drinking, and alcohol-related problems from 1983 to 1990, yet recent national reports indicate that since 1990 there has been an upsurge in substance use among adolescents. Whereas the proportion of drinkers did not significantly increase between 1990 and 1994, average consumption, heavy drinking, and alcohol-related problems all showed modest, but significant increases in the 1990s. Furthermore, between 1990 and 1994, the age distributions for alcohol use, heavy drinking, and alcohol problems changed, as evidenced by significant age by year of survey interactions. These findings indicate that adolescents are currently drinking, drinking heavily, and experiencing alcohol-related problems at younger ages than they were in past years. Prevention efforts should be targeted at delaying alcohol use in early adolescence.     

Decrease in the Prevalence of Adolescent Alcohol Use and its Possible Causes in Japan: Periodical Nationwide Cross-Sectional Surveys

Background:  Trends in alcohol drinking prevalence were assessed among Japanese adolescents, and possible reasons for a decrease in drinking prevalence observed in 2004.
Methods:  Cross-sectional nationwide surveys were conducted periodically. High schools were randomly sampled from throughout Japan in 1996, 2000, and 2004. All enrolled students in sampled schools were subjects of the surveys. Self-reporting anonymous questionnaires were collected from 115,814 students in 1996, 106,297 in 2000, and 102,451 in 2004. Questions about drinking prevalence of students and family members, proportion of students who have no friends, and sources of alcohol were included. Students who drunk at least one day of the 30 days preceding the survey were defined as the current drinkers.
Results:  The drinking prevalence in 2004 was decreased in comparison to that in 1996 and 2000 in both sexes and in all school grades. The current drinking rate (monthly drinker) among junior high school boys was 29.4% in 1996, 29.0% in 2000, and 20.5% in 2004, while that among senior high school boys was 49.7%, 48.7%, and 36.2%, respectively. The respective prevalence among junior and senior girls was 24.0%, 25.5%, and 20.0% and 40.8%, 42.1%, and 34.1%. The prevalent sources of alcohol beverages were searching in home, stores (convenience store, supermarket, or gas-stand), liquor shops, and bars. An analysis of the reasons for this decrease identified a decrease in drinking prevalence in students' families, especially by fathers and older brothers, and an increase in the proportion of students who had no friends.
Conclusions:  A decrease in drinking prevalence of male family members and a limitation of sources of alcoholic beverages may contribute to the decrease in adolescent drinking prevalence.     

Comorbidity of Alcohol Use Disorder and Chronic Pain: Genetic Influences on Brain Reward and Stress Systems

Alcohol use disorder (AUD) is highly comorbid with chronic pain (CP). Evidence has suggested that neuroadaptive processes characterized by reward deficit and stress surfeit are involved in the development of AUD and pain chronification. Neurological data suggest that shared genetic architecture associated with the reward and stress systems may contribute to the comorbidity of AUD and CP. This monograph first delineates the prevailing theories of the development of AUD and pain chronification focusing on the reward and stress systems. It then provides a brief summary of relevant neurological findings followed by an evaluation of evidence documented by molecular genetic studies. Candidate gene association studies have provided some initial support for the genetic overlap between AUD and CP; however, these results must be interpreted with caution until studies with sufficient statistical power are conducted and replications obtained. Genomewide association studies have suggested a number of genes (e.g., TBX19, HTR7, and ADRA1A) that are either directly or indirectly related to the reward and stress systems in the AUD and CP literature. Evidence reviewed in this monograph suggests that shared genetic liability underlying the comorbidity between AUD and CP, if present, is likely to be complex. As the advancement in molecular genetic methods continues, future studies may show broader central nervous system involvement in AUD–CP comorbidity.