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Background: We sought to clarify the impact of adolescent alcohol misuse on adult physical health and subjective well‐being. To do so, we investigated both the direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction and the indirect effects on these outcomes attributable to subsequent alcohol problems. Method: The sample included 2733 twin pairs (32% monozygotic; 52% female) from the FinnTwin16 study. Adolescent alcohol misuse was a composite of frequency of drunkenness, frequency of alcohol use, and alcohol problems at ages 16, 17, and 18.5. The early midlife outcomes included somatic symptoms, self‐rated health, and life satisfaction at age 34. The mediators examined as part of the indirect effect analyses included alcohol problems from the Rutgers Alcohol Problem Index at ages 24 and 34. Serial mediation and co‐twin comparison models were applied and included covariates from adolescence and early midlife. Results: There were weak direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction. However, there was stronger evidence for indirect effects, whereby young adult and early midlife alcohol problems serially mediated the relationship between adolescent alcohol misuse and early midlife somatic symptoms (β = 0.03, 95% CI [0.03, 0.04]), self‐rated health (β = −0.02, 95% CI [−0.03, −0.01]), and life satisfaction (β = −0.03, CI [−0.04, −0.02]). These serial mediation effects were robust in co‐twin comparison analyses. Conclusions: These results provide evidence that alcohol problems are a primary driver linking adolescent alcohol misuse and poor health outcomes across the lifespan. [ABSTRACT FROM AUTHOR]

Background: Do drinking patterns in late adolescence/early adulthood predict lifetime childlessness and number of children? Research on this question has been only tangentially relevant and the results inconsistent. The designs used to date have been compromised by genetic and environmental confounds that are poorly controlled; covariate effects of smoking and education that are often ignored; males being understudied; population‐based sampling rare, and long‐term prospective studies with genetically informative designs yet to be reported. Method: In a 33‐year follow‐up, we linked the drinking patterns of >3500 Finnish twin pairs, assessed at ages 18–25, to registry data on their eventual number of children. Analyses distinguished associations of early drinking patterns with lifetime childlessness from those predictive of family size. Within‐twin pair analyses used fixed‐effects regression models to account for shared familial confounds and genetic liabilities. Childlessness was analyzed with Cox proportional hazards models and family size with Poisson regression. Analyses within‐pairs and of twins as individuals were run before and after adjustment for smoking and education, and for oral contraceptive (OC) use in individual‐level analyses of female twins. Results: Baseline abstinence and heavier drinking both significantly predicted lifetime childlessness in individual‐level analyses. Few abstinent women used OCs, but they were nonetheless more often eventually childless; adjusting for smoking and education did not affect this finding. Excluding childless twins, Poisson models of family size showed heavier drinking at 18–25 to be predictive of fewer children in both men and women. Those associations were replicated in within‐pair analyses of dizygotic twins, each level of heavier drinking being associated with smaller families. Among monozygotic twins, associations of drinking with completed family size yielded effects of similar magnitude, reaching significance at the highest levels of consumption, ruling out familial confounds. Conclusions: Compared to moderate levels of drinking, both abstinence and heavier drinking in late adolescence/early adulthood predicted a greater likelihood of lifetime childlessness and eventual number of children. Familial confounds do not fully explain these associations. [ABSTRACT FROM AUTHOR]

Background: DNA methylation may play a role in the progression from normative to problematic drinking and underlie adverse health outcomes associated with alcohol misuse. We examined the association between alcohol consumption and DNA methylation patterns using 3 approaches: a conventional epigenome‐wide association study (EWAS); a co‐twin comparison design, which controls for genetic and environmental influences that twins share; and a regression of age acceleration, defined as a discrepancy between chronological age and DNA methylation age, on alcohol consumption. Methods: Participants came from the Finnish Twin Cohorts (FinnTwin12/FinnTwin16; N = 1,004; 55% female; average age = 23 years). Individuals reported the number of alcoholic beverages consumed in the past week, and epigenome‐wide DNA methylation was assessed in whole blood using the Infinium HumanMethylation450 BeadChip. Results: In the EWAS, alcohol consumption was significantly related to methylation at 24 CpG sites. When evaluating whether differences between twin siblings (185 monozygotic pairs) in alcohol consumption predicted differences in DNA methylation, co‐twin comparisons replicated 4 CpG sites from the EWAS and identified 23 additional sites. However, when we examined qualitative differences in drinking patterns between twins (heavy drinker vs. light drinker/abstainer or moderate drinker vs. abstainer; 44 pairs), methylation patterns did not significantly differ within twin pairs. Finally, individuals who reported higher alcohol consumption also exhibited greater age acceleration, though results were no longer significant after controlling for genetic and environmental influences shared by co‐twins. Conclusions: Our analyses offer insight into the associations between epigenetic variation and levels of alcohol consumption in young adulthood. [ABSTRACT FROM AUTHOR]

Background: Many adult drinkers consume far beyond the binge threshold. This "high‐intensity drinking" (HID), defined as 2 (HID‐2) and 3 (HID‐3) times the binge threshold, is of public health interest due to its role in acute alcohol‐related harms. Research on HID has mostly been limited to college‐aged young adults, focused on contextual factors, and neglected the potential role of genetic influences on the propensity to engage in HID. Methods: Structured diagnostic interviews assessing past‐year alcohol involvement were conducted with 3,785 individuals (1,365 men, 2,420 women; Mage = 32, range = 21 to 46), including 3,314 twins and 471 nontwin siblings from the Australian Twin Registry. Multinomial logistic regression analyses were conducted to compare HID‐2 and HID‐3 to binge drinking on demographic correlates, drinking characteristics, and drinking‐related consequences. Biometric modeling was conducted to estimate the role of genetic, common, and individual‐specific environmental factors in HID propensity. Results: Among past‐year drinkers, the prevalence of HID‐2 and HID‐3 was both 22%, with men disproportionally represented. The frequencies of drinking, intoxication, and binge drinking significantly increased across the heavier drinking categories, which also evidenced higher average consumption quantities and higher rates of alcohol‐related consequences. The propensity to engage in HID was significantly heritable (A = 37% [95% CI: 28 to 46%]), with individual‐specific environmental influences accounting for the remainder of the variance. Conclusions: This study convincingly demonstrates that HID is not restricted to college‐aged young adults, but also can be highly prevalent among those of working age, and that the propensity to engage in HID is partially explained by genetic influences. [ABSTRACT FROM AUTHOR]

Background: Alcohol involvement has familial associations with bulimic symptoms (i.e., binge eating, inappropriate compensatory behaviors), with several studies indicating a genetic overlap between the two. It is unclear whether overlapping familial risk with alcohol involvement extends to other eating disorder symptoms. Understanding the genetic overlap between alcohol involvement and other eating disorder symptoms may aid in more targeted interventions for comorbid alcohol use‐eating disorder symptoms. Thus, we investigated associations between alcohol involvement and 2 core eating disorder symptoms: drive for thinness and body dissatisfaction in adolescent female and male twins. Methods: We assessed 3 levels of alcohol involvement: alcohol use in the last month, having ever been intoxicated, and alcohol intoxication frequency via self‐report. The Eating Disorder Inventory‐II assessed drive for thinness and body dissatisfaction. Sex‐specific biometrical twin modeling examined the genetic overlap between alcohol involvement and eating disorder symptoms. Results: Phenotypic associations between alcohol involvement, drive for thinness, and body dissatisfaction were significantly greater in girls compared with boys. A majority of the associations between alcohol involvement, drive for thinness, and body dissatisfaction in girls, but not boys, met our threshold for twin modeling (phenotypic r > 0.20). Moderate genetic correlations were observed between the 3 aspects of alcohol involvement and drive for thinness. Moderate genetic correlations were observed between alcohol use and intoxication frequency and body dissatisfaction. Conclusions: Together with the literature on alcohol involvement and bulimic symptoms, these findings suggest a generalized association between alcohol involvement and eating disorder symptoms in girls, whereas this association may be symptom specific in boys. Genetic correlations indicate that the amount and direction of this genetic overlap differs across specific symptoms. When intervening on comorbid alcohol involvement and eating disorder symptoms, it may be important to target‐specific eating disorder symptoms. It is unclear whether alcohol involvement (AI) has familial associations with eating disorder symptoms beyond symptoms of bulimia nervosa. We investigated associations between alcohol involvement and drive for thinness (DT) and body dissatisfaction (BD) in adolescent twins using sex‐specific biometrical twin modeling. Moderate genetic correlations were observed between AI and DT. Findings suggest the amount and direction of the genetic overlap between AI and eating disorder symptoms differs across specific symptoms. [ABSTRACT FROM AUTHOR]

Background Few studies examine risk to offspring who experience both parental alcohol problems and parental separation and still fewer consider gender of the affected parent. We examined interactive effects of maternal versus paternal alcohol problems and parental separation on timing of first alcoholic drink in daughters. Methods Data were drawn from a sample of 3,539 European (or other) ancestry (EA) and 611 African ancestry (AA) female twins born between 1975 and 1985, median age 15 at first assessment. Cox proportional hazards regression models were estimated predicting age at first full drink from parental history of alcohol problems (mother only, father only, or both parents), parental separation during childhood, and the interaction of parental alcohol problems and parental separation. Cox models were estimated without and with adjustment for correlated risk factors, separately for EA and AA twins. Results For both EA and AA twins, a significant interaction between parental separation and mother-only alcohol problems was observed, suggesting reduced risk of drinking associated with mother-only alcohol problems in separated versus intact families. Conclusions Findings highlight parental separation as an important moderator of risk to children of mothers who have a history of problem drinking, with interactive effects observed consistently across racial group. To identify underlying processes, additional research is needed with more detailed characterization of separated families where mother only has a history of alcohol problems. [ABSTRACT FROM AUTHOR]

Background Resilience has been shown to be protective against alcohol use disorders (AUDs), but the magnitude and nature of the relationship between these 2 phenotypes are not clear. The aim of this study was to examine the strength of this relationship and the degree to which it results from common genetic or common environmental influences. Methods Resilience was assessed on a 9-point scale during a personal interview in 1,653,721 Swedish men aged 17 to 25 years. AUD was identified based on Swedish medical, legal, and pharmacy registries. The magnitude of the relationship between resilience and AUD was examined using logistic regression. The extent to which the relationship arises from common genetic or common environmental factors was examined using a bivariate Cholesky decomposition model. Results The 5 single items that comprised the resilience assessment (social maturity, interest, psychological energy, home environment, and emotional control) all reduced risk for subsequent AUD, with social maturity showing the strongest effect. The linear effect by logistic regression showed that a 1-point increase on the resilience scale was associated with a 29% decrease in odds of AUD. The Cholesky decomposition model demonstrated that the resilience-AUD relationship was largely attributable to overlapping genetic and shared environmental factors (57 and 36%, respectively). Conclusions Resilience is strongly associated with a reduction in risk for AUD. This relationship appears to be the result of overlapping genetic and shared environmental influences that impact resilience and risk of AUD, rather than a directly causal relationship. [ABSTRACT FROM AUTHOR]

Background Employment-related substance use can negatively affect both workplace and worker. Relationships between workplace characteristics and substance use may be explained by genetic and environmental effects; this research uses a co-twin control (discordant twin) design to disentangle these influences. Methods This study compared population-level to discordant twin pair relationships to analyze the genetic and environmental influences of work-related risks on substance use in N = 2,138 dizygotic and monozygotic male twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Negative binomial and logistic regressions were fit to predict differences in the frequency of drinking, typical and maximum number of drinks, the number of cigarettes per day, and any binge drinking or any tobacco use across occupation, work hours, job strain, problems with coworkers, and perceived job insecurity. Results In population-level analyses, several work-related variables were associated with substance use. The population-level associations of occupation with typical and maximum drinks per day and of problems with coworkers to binge drinking were not significant at the twin level. At both the population and discordant twin levels, only higher occupational status was associated with a lower likelihood of regular tobacco use ( odds ratio 0.44, 95% confidence interval 0.21, 0.94). Conclusions Variation in genes and shared environment appears to account for many of the population-level relationships between work-related stressors and substance use. Work stressors may not be the most fruitful intervention point when aiming to reduce alcohol or tobacco use, although men in certain high-stress occupations may be at greater risk for substance use. [ABSTRACT FROM AUTHOR]

Background Self-harm has considerable societal and economic costs and has been extensively studied in relation to alcohol involvement. Although early onset alcohol use ( EAU) has been causally linked to maladaptive clinical outcomes, its association with self-harm is less well characterized. This study aimed to further examine the link between EAU and both nonsuicidal self-injury ( NSSI) and suicide attempt ( SA), and elucidate shared familial and causal/individual-specific pathways that explain this co-occurrence. Methods Using data from 6,082 Australian same-sex twin pairs (1,732 monozygotic [MZ] and 1,309 dizygotic [DZ]), ages 23 to 40, we examined prevalence rates of NSSI and SA among twin pairs concordant and discordant for EAU. Conditional logistic regression, controlling for early clinical covariates and the influence of zygosity on EAU, was used to examine the odds ratio ( OR) of self-harm within twin pairs discordant for EAU. Results Prevalence rates of both NSSI and SA were highest among twin pairs concordant for EAU and for twins who reported EAU within discordant twin pairs. Results from discordant twin analyses revealed nearly 4-fold increased odds of SA for the twin who endorsed EAU, and this OR was equal across MZ and DZ twins. EAU also was associated with elevated odds of NSSI ( OR = 7.62), although this was only the case for DZ twins in discordant pairs. Conclusions The equivalent increase in odds of SA for both MZ and DZ twins suggests that causal or individual-specific influences explain the link between EAU and SA. For NSSI, elevated odds for DZ twins and nonsignificant findings for MZ twins implicate correlated genetic factors in the association between EAU and NSSI. Future studies should test mechanisms through which EAU may causally influence SA, as well as examine whether genetic risk for third variables (e.g., negative urgency, stress reactivity) may explain the genetic overlap between EAU and NSSI. [ABSTRACT FROM AUTHOR]

Background We examined associations between parental separation during childhood and offspring alcohol involvement, adjusting for genetic and environmental risks specific to parental alcohol (AD) and cannabis/other illicit drug dependence (DD). Methods The sample consisted of 1,828 offspring of male twins from the Vietnam Era Twin (VET) Registry, who completed a telephone diagnostic interview. Cox proportional hazards regression analyses were conducted predicting onset of first use, transition from first use to first AD symptom, and transition from first use to AD diagnosis from paternal and avuncular AD and DD history, parental separation, and offspring and family background characteristics. Paternal/avuncular DD/AD was based on the DSM-III-R; offspring and maternal AD were based on DSM-IV criteria. Results Paternal DD/AD predicted increased offspring risk for all transitions, with genetic effects suggested on rate of transitioning to AD diagnosis. Parental separation was predictive of increased risk for early alcohol use, but a reduced rate of transition to both AD symptom onset and onset of AD. No interactions between separation and familial risk (indexed by paternal or avuncular DD/AD) were found. Conclusions Findings highlight the contribution of both parental separation and paternal substance dependence in predicting timing of offspring alcohol initiation and problems across adolescence into early adulthood. [ABSTRACT FROM AUTHOR]

Background We sought to develop an empirical, broad-based developmental model for sex differences in risk for symptoms of alcohol use disorders, here called alcohol problems ( APs). Methods We assessed 18 risk factors in 5 developmental tiers in both members of 1,377 opposite-sex dizygotic twin pairs from the Virginia population-based twin registry. Analyses were conducted by structural modeling, examining within-pair differences. Results The best-fitting model explained 73% of the variance in men and 71% in women for last year AP. Forty-nine percent of paths differed significantly across sexes. Ten variables had appreciably different predictive effects on AP in males versus females. Three were stronger in females: familial risk, early-onset anxiety disorders, and nicotine dependence. Seven predictors had a stronger total effect in males: novelty seeking, conduct disorder, childhood sexual abuse, parental loss, neuroticism, low self-esteem, and low marital satisfaction. Conclusions In a co-twin control design, which matches sisters and brothers on genetic and familial-environmental background, we found numerous sex differences in predictors of last year AP. Factors that were more prominent in men and in women were diverse, reflecting both internalizing and externalizing psychopathology. The model was slightly more successful at predicting AP in men than in women. [ABSTRACT FROM AUTHOR]

Background Much is unknown about the relationship between socioeconomic status ( SES) and alcohol use, including the means by which SES may influence risk for alcohol use. Methods Using a sample of 672 twin pairs (aged 25 to 74) derived from the MacArthur Foundation Survey of Midlife Development in the United States, this study examined whether SES, measured by household income and educational attainment, moderates genetic and environmental influences on 3 indices of alcohol use: amount used, frequency of use, and problem use. Results We found significant moderation for amount of alcohol used. Specifically, genetic effects were greater in low- SES conditions, shared environmental effects (i.e., environmental effects that enhance the similarity of twins from the same families) tended to increase in high- SES conditions, and nonshared environmental effects (i.e., environmental effects that distinguish twins) tended to decrease with SES. This pattern of results was found for both income and education, and it largely replicated at a second wave of assessment spaced 9 years after the first. There was virtually no evidence of moderation for either frequency of alcohol use or alcohol problems. Conclusions Our findings indicate that genetic and environmental influences on drinking amount vary as a function of the broader SES context, whereas the etiologies of other drinking phenomena are less affected by this context. Efforts to find the causes underlying the amount of alcohol used are likely to be more successful if such contextual information is taken into account. [ABSTRACT FROM AUTHOR]

Background Alcohol consumption is typically correlated with the alcohol use behaviors of one's peers. Previous research has suggested that this positive relationship could be due to social selection, social influence, or a combination of both processes. However, few studies have considered the role of shared genetic and environmental influences in conjunction with causal processes. Methods This study uses data from a sample of male twins ( N = 1,790) who provided retrospective reports of their own alcohol consumption and their peers' alcohol-related behaviors, from adolescence into young adulthood (ages 12 to 25). Structural equation modeling was employed to compare 3 plausible models of genetic and environmental influences on the relationship between phenotypes over time. Results Model fitting indicated that one's own alcohol consumption and the alcohol use of one's peers are related through both genetic and shared environmental factors and through unique environmental causal influences. The relative magnitude of these factors, and their contribution to covariation, changed over time, with genetic factors becoming more meaningful later in development. Conclusions Peers' alcohol use behaviors and one's own alcohol consumption are related through a complex combination of genetic and environmental factors that act via correlated factors and the complementary causal mechanisms of social selection and influence. Understanding these processes can inform risk assessment as well as improve our ability to model the development of alcohol use. [ABSTRACT FROM AUTHOR]

Background Both alcohol-specific genetic factors and genetic factors related to externalizing behavior influence problematic alcohol use. Little is known, however, about the etiologic role of these 2 components of genetic risk on alcohol-related behaviors across development. Prior studies conducted in a male cohort of twins suggest that externalizing genetic factors are important for predicting heavy alcohol use in adolescence, whereas alcohol-specific genetic factors increase in importance during the transition to adulthood. In this report, we studied twin brothers and sisters and brother-sister twin pairs to examine such developmental trajectories and investigate whether sex and cotwin sex effects modify these genetic influences. Methods We used prospective, longitudinal twin data collected between ages 12 and 22 within the population-based FinnTwin12 cohort study (analytic n = 1,864). Our dependent measures of alcohol use behaviors included alcohol initiation (age 12), intoxication frequency (ages 14 and 17), and alcohol dependence criteria (age 22). Each individual's genetic risk of alcohol use disorders ( AUD- GR) was indexed by his/her parents' and cotwin's DSM- IV Alcohol Dependence ( AD) criterion counts. Likewise, each individual's genetic risk of externalizing disorders ( EXT- GR) was indexed with a composite measure of parents' and cotwin's DSM- IV Conduct Disorder and Antisocial Personality Disorder criterion counts. Results EXT- GR was most strongly related to alcohol use behaviors during adolescence, while AUD- GR was most strongly related to alcohol problems in young adulthood. Further, sex of the twin and sex of the cotwin significantly moderated the associations between genetic risk and alcohol use behaviors across development: AUD- GR influenced early adolescent alcohol use behaviors in females more than in males, and EXT- GR influenced age 22 AD more in males than in females. In addition, the associations of AUD- GR and EXT- GR with intoxication frequency were greater among 14- and 17-year-old females with twin brothers. Conclusions We found divergent developmental trajectories for alcohol-specific and externalizing behavior-related genetic influences on alcohol use behaviors; in early adolescence, genetic influences on alcohol use behaviors are largely nonspecific, and later in adolescence and young adulthood, alcohol-specific genetic influences on alcohol use are more influential. Importantly, within these overall trajectories, several interesting sex differences emerged. We found that the relationship between genetic risk and problematic drinking across development is moderated by the individual's sex and his/her cotwin's sex. AUD- GR influenced adolescent alcohol outcomes in females more than in males and by age 22, EXT- GR influenced AD criteria more for males than females. In addition, the association between genetic risk and intoxication frequency was greater among 14- and 17-year-old females with male cotwins. [ABSTRACT FROM AUTHOR]

Background Adolescent alcohol abuse is associated with adverse outcomes in early adulthood, but differences in familial status and structure and household and community environments correlate with both adolescent drinking and adverse adult outcomes and may explain their association. We studied drinking-discordant twin pairs to evaluate such confounds to ask: Will between-family associations replicate in within-family comparisons? Methods With longitudinal data from >3,000 Finnish twins, we associated drinking problems at age 18½ with 13 outcomes assessed at age 25; included were sustained substance abuse, poor health, physical symptoms, early coital debut, multiple sexual partners, life dissatisfaction, truncated education, and financial problems. We assessed associations among twins as individuals with linear regression adjusted for correlated observations; within-family analyses of discordant twin pairs followed, comparing paired means for adult outcomes among co-twins discordant for adolescent problem drinking. Defining discordance by extreme scores on self-reported problem drinking at age 18½ permitted parallel analyses of twins as individuals and discordant twin pairs. Alternate definitions of pair-wise discordance and difference score correlations across the entire twin sample yielded supplementary analyses. Results All individual associations were highly significant for all definitions of discordance we employed. Depending on definitions of discordance, 11 to 13 comparisons of all drinking-discordant twin pairs and 3 to 6 comparisons of discordant monozygotic (MZ) twin pairs replicated between-family associations. For most outcomes, effect size attenuated from individual-level analysis to that within discordant MZ twin pairs providing evidence of partial confounding in associations reported in earlier research. The exception was the General Health Questionnaire (GHQ); at age 25, GHQ-12 had equivalent associations with age 18½ Rutgers Alcohol Problem Index across all comparisons. Conclusions Our analyses control for shared family background, and, partly or fully, for shared genes, to yield within-family replications and more compelling evidence than previously available that adolescent alcohol abuse disrupts transitions into early adulthood. [ABSTRACT FROM AUTHOR]

Background Alcohol consumption is influenced by heritable factors. The genetic influence on usual high-density drinking, including alcohol intoxication and hangover, is unknown. We aim to estimate the heritability of usual high-density drinking. Methods A total of 13,511 male twins in this cross-sectional study were included from the National Academy of Sciences-National Research Council ( NAS- NRC) Twin Registry. Data on the frequency of alcohol intoxication and alcohol hangover over the past year, that is, usual high-density drinking (phenotypes), were collected through a self-administered questionnaire when twins were middle-aged in 1972. Structural equation modeling was used to estimate the variance components of phenotypes. Results The mean of the frequency of usual high-density drinking in the entire twin population was 0.16 times per month for intoxication and 0.18 times per month for hangover. The heritability of usual alcohol intoxication was 50.7% (95% confidence interval [CI] 46.2 to 55.0) before and 49.9% (95% CI 45.3 to 54.2) after the body mass index ( BMI) adjustment. The heritability of usual hangover was 55.4% (95% CI 51.2 to 58.6) before and 54.8% (95% CI 50.6 to 58.8) after adjustment for BMI. Unshared environmental factors between co-twins explained the remaining variance in alcohol intoxication and in hangover. Conclusions Both genetic and unshared environmental factors have important influences on usual alcohol intoxication and hangover. These findings are important in understanding the occurrence of and developing interventions for usual high-density drinking. [ABSTRACT FROM AUTHOR]

Background Studies suggest that better cognitive and verbal abilities in childhood predict earlier experimentation with alcohol and higher levels of drinking in adolescence, whereas poorer ability is related to a higher likelihood of remaining abstinent. Whether individual differences in language development in childhood predict differences in adolescent drinking behaviors has not been studied. Methods To address that question, we compared co-twins from twin pairs discordant for their childhood language development and studied associations of parental reports of within-pair differences in age at speaking words, age at learning to read, and expressive language skills during school age with self-reported within-pair differences in drinking, intoxication, and alcohol-related problems across adolescence and young adulthood. Data from 2 longitudinal population-based samples of twin families were used, with verbal developmental differences in childhood reported by the parents when the twins were 12 and 16 years of age, respectively. Results Conditional logistic regression analyses and within-pair correlation analyses suggested positive associations between verbal development and drinking behaviors in both data sets. In analyses adjusted for birth order and birth weight, the co-twin reported to be verbally more advanced in childhood tended to report more frequent drinking and intoxication in adolescence in both samples. Better verbal development also was associated with the likelihood of having friends who drink in adolescence. Conclusions These findings suggest that, adjusting for familial and other factors shared by co-twins, better verbal development in childhood predicts more frequent drinking and intoxication in adolescence and young adulthood, possibly due, in part, to peer associations. [ABSTRACT FROM AUTHOR]

Background High levels of various forms of social support (e.g., romantic partner, family, friend) have a buffering effect on alcohol use outcomes in both adolescents and adults. The etiological associations among these variables have not been well studied. One possibility is that social support may buffer against inherited genetic predispositions to alcohol problems. Previous work has examined gene-environment interactions (G×E) for alcohol use disorders, but never for social support in adult twins. Methods In the current study, biometric modeling techniques were implemented to examine genetic and environmental components of variance of social support and alcohol use problems in a sample of 672 adult twin pairs. Using biometric moderation models that estimate G×E in the presence of gene-environment correlation ( rGE), analyses examined how genetic and environmental influences on alcohol use problems varied as a function of romantic partner support, family support, and friend support. Results Genetic and environmental components of variance for alcohol use problems varied depending on the level of romantic partner support, with greater environmental influences found at the low level of support. Family and friend support, however, failed to show moderating effects. Conclusions The current research has implications for expanding our understanding of what types of social support may trigger or suppress genetic and environmental influences on alcohol use problems. [ABSTRACT FROM AUTHOR]

Background Differences in age at initiation of alcohol use and rates of problem drinking between African Americans and European Americans are well documented, but the association between early and problem use-and distinctions by ethnic group in this association-have yet to be examined in a genetically informative framework. Methods Data were derived from a longitudinal study of female twins in Missouri. The sample was composed of 3,532 twins (13.6% African-American [AA], 86.4% European-American [EA]), who participated in the fourth wave of data collection and reported consumption of at least 1 alcoholic drink over the lifetime. Mean age at Wave 4 was 21.7 (range = 18 to 29) years. Twin modeling was conducted to estimate the relative contributions of additive genetic (A), shared environmental (C), and unique environmental (E) factors to variation in age at first drink and problem alcohol use and the cross-phenotype overlap in these influences. Results Early initiation of alcohol use predicted problem use in EA but not AA women. Separate AA and EA twin models produced substantially different estimates (but not statistically different models) of the relative contributions of A and C to problem alcohol use but similar genetic correlations between the phenotypes. Whereas 33% of the variance in the EA model of problem use was attributed to C, no evidence for C was found in the AA model. Heritability estimates for problem alcohol use were 41% in the AA model, 21% in the EA model. Evidence for A and C were found in both AA and EA models of age at first drink, but the A estimate was higher in the EA than AA model (44% vs. 26%). Conclusions Findings are suggestive of distinctions between AA versus EA women in the relative contribution of genetic and environmental influences on the development of problem drinking. [ABSTRACT FROM AUTHOR]

Background Sense of mastery, a personal resource, is likely to have an inverse association with alcohol dependence. Previous evidence, however, is sparse. In addition, the extent to which an association is due to genetic or environmental factors is unknown. Methods Data were from 3,983 male twins and 2,630 female twins who had ever used alcohol, interviewed in the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Mastery was measured by a 6-item scale. Lifetime diagnosis of alcohol dependence was based on DSM- IV criteria assessed in a structured diagnostic interview. Univariate analyses modeled the relative contributions of genetic and environmental factors to mastery and alcohol dependence using Mx software. Bivariate Cholesky models were fit to the mastery and alcohol dependence raw data. Results In the best-fitting model of mastery, genetic factors accounted for about 33% of the observed variance. Nonshared environmental factors, including random measurement error, accounted for the remaining 67%. Fifty-six percent of the variance in liability to alcohol dependence was genetic, and the other 44% was explained by the nonshared environment. The phenotypic polychoric correlation between mastery and alcohol dependence of −0.18 was primarily (67% in the best-fitting model) explained by genes common to both low mastery and alcohol dependence; the rest was explained by nonshared environmental factors. Conclusions The findings indicate that genetic risk for alcohol dependence overlaps with genetic factors that influence sense of mastery. Key challenges for future research are to identify the genes that influence mastery and alcohol dependence, as well as the environmental pathways by which they come to be linked. [ABSTRACT FROM AUTHOR]

Background The effects of sibship size and structure on delinquency are well established. Specifically, having a large family and many brothers has been shown to predict offending. However, despite strong links between delinquency and alcohol use, the contribution of sibship factors to drinking behaviors remains largely unexplored. The current study investigated the impact of sibship size and composition on younger brothers' and sisters' ages of drinking and intoxication onset. Methods We employed a sample of 4,281 same-sex twins from the Australian Twin Register to examine whether (i) large sibship size facilitates earlier age at first drink ( AFD) and age at first intoxication ( AFI) in males and females, (ii) having many older brothers predicts earlier ages of AFD and AFI in males, and (iii) having many older brothers results in later AFD and AFI in females. We tested whether effects were moderated by parental divorce and alcohol misuse and mediated by familial religion. Results Sibling effects were minimal before accounting for family context. However, when parental divorce and excessive parental drinking were included as moderators, sibling effects were significantly amplified among individuals from homes of divorce, and effects were strongest when siblings were close in age. Conclusions Strong close in age older sibling effects indicate that proximal sibling attitudes and behaviors about alcohol likely interact with structural factors to influence younger siblings' drinking. Sibship factors were much more influential in one population (individuals from homes of divorce) than another (respondents with a parental history of excessive drinking), suggesting that sibling effects vary depending on the type of co-occurring familial risk. Prevention efforts performed at the family level, and introduced before first use of alcohol, are likely to delay drinking initiation and help prevent future alcohol problems. [ABSTRACT FROM AUTHOR]

Background There are robust sex differences for alcohol phenotypes, with men reporting more drinking and alcohol use disorder ( AUD) symptoms than women. However, the sources of these effects are not completely understood. Sex hormones, a substantial biological sex difference, exert neurobehavioral influences and are candidates for influencing sex differences in alcohol phenotypes. This study investigated the effects of prenatal androgens based on the hypothesis of prenatal hormone transfer, which posits that hormones from one twin influence the development of a cotwin. Methods This study compared female twins from opposite-sex ( OSF) and same-sex ( SSF) pairs to investigate associations between prenatal androgens and alcohol phenotypes. Additional analyses distinguished prenatal and postnatal effects by comparing OSFs and SSFs with a close-in-age older ( CAO) brother. Results OSFs endorsed more lifetime AUD symptoms than SSFs ( d = 0.14). Females with a CAO brother reported greater intoxication frequency ( d = 0.35), hangover frequency ( d = 0.24), typical drinking quantity ( d = 0.33), and max drinks (i.e., the most drinks ever consumed in a 24-hour period; d = 0.29). Controlling for postnatal effects, OSFs still endorsed more lifetime AUD symptoms than SSFs with a CAO brother ( d = 0.16). Conclusions Prenatal exposure to a male cotwin was associated with increases in AUD symptoms, above the effect of postnatal exposure to a male sibling. Prenatal exposure to a male cotwin was not associated with increases in other alcohol-related phenotypes, but postnatal exposure to older male siblings produced medium effect sizes for indicators of alcohol consumption. Sex differences in AUDs, but not alcohol use, may be partially due to the neurodevelopmental effects of prenatal androgens. However, sibling effects may be larger than any effect of prenatal androgen exposure. [ABSTRACT FROM AUTHOR]

Background Adolescence is characterized by higher levels of novelty-seeking and risk-taking behavior, including initiation of alcohol use. Also, there is considerable heterogeneity in the change and continuity of alcohol use over time, which emphasizes the need to examine factors predicting alcohol use and the patterns of use over time. Methods Retrospective data on average monthly alcohol use and risk and protective factors were obtained through interviews and questionnaires in 1,560 adult male twins. Latent class growth analysis in Mplus was performed on data of alcohol use over ages 15 to 36. Second, logistic regression analyses were used to associate risk and protective characteristics with membership in distinct latent trajectories of alcohol use. Results Six trajectories of alcohol use were identified, varying in the level of alcohol use, the rate of change in use in early adolescence and the persistence of use into adulthood. Genetic risk of externalizing disorder and peer deviance showed the greatest risks for unfavorable alcohol trajectories with higher levels of use and higher rates of early increase in use. Parental monitoring and involvement in social activities showed protective effects. Involvement in religious activities was strongly associated with reduced persistence of high-level drinking in univariate but not multivariate regression analyses. Conclusions Risk and protective factors impacted differentially on level of alcohol use, rate of increase in use during adolescence, and persistence of heavy alcohol use over time. Insight into the different ways in which predictors impact on alcohol use is relevant for the development of new intervention strategies. For this purpose, causality of the associations should be further examined. [ABSTRACT FROM AUTHOR]

Background Proposed changes to the upcoming DSM-5 include the following: (i) combining criteria for DSM- IV alcohol abuse ( AA) and alcohol dependence ( AD) into 1 diagnostic category (alcohol use disorder [ AUD]); (ii) exclusion of the 'legal problems' ( LP) criterion; and (iii) addition of a 'craving' criterion. Few published studies empirically assess the potential consequences of the proposed changes. Methods Using a population-based sample of twins assessed for lifetime AA/ AD diagnoses, we explored phenotypic differences across DSM- IV and a modified DSM-5 diagnoses without craving because of its unavailability in the data set. We used factor analysis and item response theory ( IRT) to evaluate the potential consequences of excluding the LP criterion from AUD and used twin modeling to examine genetic differences between DSM- IV and the modified DSM-5 diagnoses. Results The prevalence of AUD was slightly higher than that of DSM- IV diagnoses. Individuals meeting DSM- IV or DSM-5 criteria, but not both, exhibit fewer comorbid diagnoses than those meeting both sets of criteria. Individuals meeting only DSM-5 criteria were slightly less severely affected than those meeting only DSM- IV criteria. Factor analysis indicated that the LP criterion loading is the lowest of all symptoms; IRT analysis suggested that this criterion has low discriminatory power. The genetic correlation between DSM- IV and DSM-5 diagnoses was slightly but significantly lower than unity. Conclusions The proposed DSM-5 AUD criteria are unlikely to result in significant changes in prevalence of diagnosed alcohol problems. However, it is unclear whether the new criteria represent a more valid diagnosis: new cases are no more severely affected than DSM- IV-only cases. Given the psychometric properties of LP, its exclusion should not negatively impact diagnostic validity. Similarly, the stable heritability across DSM- IV and DSM-5 diagnoses suggests that the proposed changes will not have substantial negative consequences in terms of familial influences, a key validator. These results provide equivocal empirical support for the proposed DSM-5 changes for AUDs. [ABSTRACT FROM AUTHOR]

Background Alcohol use disorders ( AUDs) are clinically heterogeneous and strongly influenced by familial/genetic factors. Can we identify specific clinical features of AUDs that index familial liability to illness? Methods In twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders meeting DSM- IV criteria for lifetime AUDs, we examined whether clinical features of AUDs, including individual DSM- IV criteria for alcohol dependence ( AD) and alcohol abuse ( AA), predicted risk for AUDs in cotwins and/or parents. Analyses of individual criterion were repeated controlling for the total number of endorsed criteria. Results Across these analyses, examining narrowly and broadly defined AUDs, risk of AUDs in relatives was more consistently predicted by abuse criteria than by dependence criteria, and by criteria reflecting negative psychosocial consequences rather than pharmacologic/biological criteria. Age at onset (AAO) poorly predicted risk in relatives. AUD associated legal problems, the one criterion slated for removal in DSM-5, was the most consistent single predictor of familial risk. Associations observed between individual criteria and risks of illness in relatives were generally stronger in monozygotic than dizygotic twin pairs, suggesting that these symptoms reflect a genetic risk for AUDs. Conclusions Individual DSM- IV criteria for AA and AD differ meaningfully in the degree to which they reflect the familial/genetic liability to AUDs. Contrary to expectation, the familial/genetic risk to AUDs was better reflected by symptoms of abuse and negative psychosocial consequences of AUD than by early AAO, or symptoms of tolerance and withdrawal. [ABSTRACT FROM AUTHOR]

Background Variation in alcohol metabolism affects the duration of intoxication and alcohol use. While the majority of genetic association studies investigating variation in alcohol metabolism have focused on polymorphisms in alcohol or aldehyde dehydrogenases, we have now tested for association with genes in alternative metabolic pathways that catalyze the carbon skeleton of ethanol ( EtO H) and NADH reoxidation. Methods Nine hundred fifty single nucleotide polymorphisms ( SNPs) spanning 14 genes ( ACN9, ACSS1, ACSS2, ALDH1A1, CAT, CYP2E1, GOT1, GOT2, MDH1, MDH2, SLC25A10, SLC25A11, SLC25A12, SLC25A13) were genotyped in 352 young adults who participated in an alcohol challenge study. Traits tested were blood alcohol concentration (BAC), breath alcohol concentration (BrAC), peak alcohol concentration, and rates of alcohol absorption and elimination. Allelic association was tested using quantitative univariate and multivariate methods. Results A CYP 2 E 1 promoter SNP (rs4838767, minor allele frequency 0.008) exceeded the threshold for study-wide significance (4.01 × 10−5) for 2 early BAC, 8 Br AC measures, and the peak Br AC. For each phenotype, the minor C allele was related to a lower alcohol concentration, most strongly for the fourth Br AC ( p = 2.07 × 10−7) explaining ~8% of the phenotypic variance. We also observed suggestive patterns of association with variants in ALDH1 A 1 and on chromosome 17 near SLC25 A 11 for aspects of blood and breath alcohol metabolism. An SNP upstream of GOT1 (rs2490286) reached study-wide significance for multivariate BAC metabolism ( p = 0.000040). Conclusions Overall, we did not find strong evidence that variation in genes coding for proteins that further metabolize the carbon backbone of acetaldehyde, or contribute to mechanisms for regenerating NAD from NADH, affects alcohol metabolism in our European-descent subjects. However, based on the breath alcohol data, variation in the promoter of CYP2 E 1 may play a role in preabsorptive or early hepatic alcohol metabolism, but more samples are required to validate this finding. [ABSTRACT FROM AUTHOR]

Background Although substance use is associated with reduced educational attainment, this association may be owing to common risk factors such as socioeconomic disadvantage. We tested whether alcohol, nicotine, and illicit drug use and dependence were associated with lifetime educational attainment after controlling for familial background characteristics. Methods Data were from a 1987 questionnaire and a 1992 telephone diagnostic interview of 6,242 male twins ( n = 3,121 pairs; mean age = 41.9 years in 1992) who served in the U. S. military during the Vietnam era and therefore, were eligible for educational benefits after military service. Reduced educational attainment (<16 years) was examined in twin pairs discordant for substance use history. Substance use and dependence risk factors assessed were early alcohol and cannabis use, daily nicotine use, lifetime cannabis use, and alcohol, nicotine, cannabis, and any illicit drug dependence. Results Three significant differences were observed between at-risk twins and their cotwins: Compared to their low-risk cotwins, likelihood of completing <16 years of education was significantly increased for the following: (i) twins who used alcohol before age 18 (adjusted OR = 1.44; 95% CI: 1.02 to 2.05), (ii) twins with a lifetime alcohol dependence diagnosis (adjusted OR = 1.76; 95% CI: 1.27 to 2.44), and (iii) twins who had used nicotine daily for 30 or more days (adjusted OR = 2.54, 95% CI: 1.55 to 4.17). However, no differences in education were observed among twin pairs discordant for cannabis initiation, early cannabis use, or cannabis, nicotine, or any illicit drug dependence. Conclusions Even in a veteran population with access to military educational benefits, early alcohol use, alcohol dependence, and daily nicotine use remained significantly associated with years of education after controlling for shared familial contributions to educational attainment. The association between other substances and educational attainment was explained by familial factors common to these substance use phenotypes and adult educational attainment. [ABSTRACT FROM AUTHOR]

Background: Although there is a long tradition in alcoholism research of using family history ratings, the interpretability of family history reports of alcoholism from general community samples has yet to be established. Methods: Telephone interview data obtained from a large cohort of female like-sex twins ( N = 3,787, median age 22) and their biological parents ( N = 2,928, assessed at twins' median age 15) were analyzed to determine agreement between parent self-report, parent ratings of coparent, and twin narrow (alcohol problems) and broad (problem or excessive drinking) ratings of each parent. Results: In European ancestry ( EA) families, high tetrachoric correlations were observed between twin and cotwin ratings of parental alcohol problems, between twin and parent ratings of coparent alcohol problems using symptom-based and single-item assessments, as well as moderately high correlations between twin and both mother and father self-reports. In African American ( AA) families, inter-rater agreement was substantially lower than for EA families, with no cases where father ratings of maternal alcohol problems agreed with either twin ratings or mother self-report, and both cotwin agreement and mother-twin agreement were reduced. Differences between EA and AA families were not explained by differences in years of cohabitation with father or mother's education; however, underreporting of problems by AA parents may have contributed. Conclusions: Results support the use of family history ratings of parental alcoholism in general community surveys for EA families, but suggest that family history assessment in AA families requires improved methods. [ABSTRACT FROM AUTHOR]

Background: A study by Dawson and colleagues (Alcohol Clin Exp Res 2007; 31:69) using data from National Epidemiologic Survey on Alcohol and Related Condition found earlier drinking onset age, and higher levels of past-year stressful life events (SLE) were associated with higher past-year alcohol consumption. The aims of our study were as follows: (i) to attempt to replicate this interaction; (ii) to extend it by examining sex and event dependence as potential moderators of the effect; and (iii) to estimate the roles of genetic and environmental factors in mediating the overlap of early drinking onset and SLE in their relations with alcohol consumption. Methods: Data were from 1,382 female and 2,218 male drinkers interviewed as part of the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Regression models were used to evaluate the main and interactive effects of early drinking onset and moderate or severe past-year SLE on past-year drinking density (PYDD), a weighted quantity-frequency measure of alcohol consumption. Analyses adjusted for demographic covariates and were stratified by sex and whether SLE were independent or dependent on the person's actions, as rated by interviewers. Structural twin models were used to estimate the degree to which early drinking onset, SLE, and their interaction accounted for additive genetic, common environmental and individual-specific variance in PYDD. Results: We replicated the prior finding of a main effect of higher alcohol consumption among individuals reporting earlier drinking onset. Age at drinking onset accounted for about 5% of the variation in PYDD, and this association was mostly attributable to overlapping genetic influences. Evidence for an interaction between onset age and SLE was generally weak, possibly because of lower power and other methodological differences from Dawson and colleagues' study. However, there was some evidence consistent with an interaction of higher PYDD among early drinking men who experienced independent SLE and early drinking women with dependent SLE. Conclusions: We confirmed prior findings of an association between early age at drinking onset with higher past-year drinking among young- and middle-aged adults and found limited evidence supporting a replication for higher stress-related drinking among early-onset drinkers. The association is consistent with early onset and stress-related drinking being attributable to overlapping genetic liability. Among early drinkers, our results suggest sex differences in consumption with regard to event dependence. [ABSTRACT FROM AUTHOR]

Background: Prior efforts to examine the course of drinking from onset to midlife have been limited to analyses of year-to-year changes in alcohol dependence (AD). The current investigation sought to examine the course of drinking over this time frame using consumption-based measures of drinking and evaluate the degree of comparability in trajectories estimated from diagnostic and quantity-frequency data. Methods: Participants included 420 men with a lifetime history of AD who were drawn from the Vietnam Era Twin Registry and administered the Lifetime Drinking History, which provided person-year (retrospective) data on patterns of consumption and diagnostic symptoms from drinking onset to participants' current age. Consumption-based data were aggregated into age categories that ranged from 'up to age 20' to 'ages 54 to 56' and analyzed separately as a dichotomous measure of 'heavy drinking (HD)' and continuous quantity-frequency index (QFI) scores. Results: Using latent growth mixture modeling, trajectories based on the HD measure were moderately concordant with those based on changes in AD that were previously identified in this sample, whereas trajectories based on QFI scores were only weakly related to those based on AD diagnoses. Moreover, examination of the degree of concordance between AD- and QFI-derived trajectories revealed that measures of consumption (and potentially other continuous indices of drinking) may qualify past interpretations of various developmental trajectories that have been discussed in the alcoholism typology literature (particularly 'Late Onset' alcoholism). Conclusions: Collectively, the findings highlight the importance of integrating repeated measures of alcohol consumption in future efforts to describe the course of drinking across the life span. [ABSTRACT FROM AUTHOR]

Background: Motivational models of alcohol use propose that the motivation to consume alcohol is the final common pathway to its use. Both alcohol consumption and drinking motives are influenced by latent genetic factors that partially overlap. This study investigated whether drinking motives mediate the associations between alcohol consumption and 2 single-nucleotide polymorphisms (SNPs) from genes involved in serotonin (TPH2; rs1386496) and dopamine synthesis (DDC; rs3779084). Based on earlier work showing that enhancement and coping motives were heritable in regular smokers but not in nonregular smokers, we hypothesized these motives would mediate the relationships between alcohol consumption and these SNPs in regular smokers. Methods: Drinking motives data were available from 830 young adult female twins ( n = 344 regular smokers and n = 486 never/nonregular smokers). We used confirmatory factor analyses to model enhancement, coping, and alcohol consumption factors and to conduct mediation analyses in the regular smoker and never/nonregular smoker groups. Results: Our hypothesis was partially supported. The relationship between alcohol consumption and rs1386496 was not mediated by drinking motives in either group. However, in the regular smokers, the relationship between alcohol consumption and rs3779084 was mediated by enhancement and coping motives. Carriers of the rs3779084 minor allele who were regular smokers reported more motivation to consume alcohol. Given this pattern of results was absent in the never/nonregular smokers, our results are consistent with a gene × smoking status interaction. Conclusions: In regular smokers, variability at the locus marked by rs3779084 in the DDC gene appears to index biologically based individual differences in the motivation to consume alcohol to attain or improve a positive affective state or to relieve a negative one. These results could be because of increased sensitivity to the reinforcing effects of alcohol among minor allele carriers who smoke, which might be due to structural or functional differences in mesorticolimic dopamine 'reward' circuitry. [ABSTRACT FROM AUTHOR]

Background: Twin studies demonstrate that measures of alcohol consumption (AC) show evidence of genetic influence, suggesting they may be useful in gene identification efforts. The extent to which these phenotypes will be informative in identifying susceptibility genes involved in alcohol dependence depends on the extent to which genetic influences are shared across measures of AC and alcohol problems. Previous studies have demonstrated that AC reported for the period of heaviest lifetime drinking shows a large degree of genetic overlap with alcohol dependence; however, many studies with genetic material assess current AC. Further, there are many different aspects of AC that can be assessed (e.g., frequency of use, quantity of use, and frequency of intoxication). Methods: Here, we use data from 2 large, independent, population-based twin samples, FinnTwin 16 and The Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, to examine the extent to which genetic influences are shared across many different measures of AC and alcohol problems. Results: Genetic correlations across current AC measures and alcohol problems were high across both samples. However, both samples suggest a complex genetic architecture with many different genetic factors influencing various aspects of current AC and problems. Conclusions: These results suggest that careful attention must be paid to the phenotype in efforts to 'replicate' genetic effects across samples or combine samples for meta-analyses of genetic effects influencing susceptibility to alcohol-related outcomes. [ABSTRACT FROM AUTHOR]

Background: Genetic risk for alcohol dependence has been shown to overlap with genetic factors contributing to variation in dimensions of personality. Although drinking motives have been posited as important mediators of the alcohol-personality relation, the extent to which the genetic covariance between alcohol use disorder (AUD) symptoms (i.e., abuse and dependence criteria) and personality is explained by genetic factors contributing to variation in drinking motives remains unclear. Methods: Using data from 2,904 young adult female twins, the phenotypic and genetic associations between personality dimensions (constraint [measured by the Multidimensional Personality Questionnaire; Tellegen A, 1982 unpublished data], conscientiousness, neuroticism, and agreeableness [measured by the NEO-PI; ]), internal drinking motives (enhancement and coping motives [measured by the Drinking Motive Questionnaire; ]), and AUD symptoms were tested. Results: Significant genetic associations were found between all personality measures and AUD symptoms. Coping motives showed significant genetic overlap with AUD symptoms and most personality measures, whereas enhancement motives were not significantly heritable. Adjusting for coping motives, genetic correlations between AUD symptoms and traits of neuroticism and agreeableness were no longer statistically significant. Conclusions: Findings suggest that genetic variation in drinking to cope might account for a considerable proportion of the genetic covariance between specific personality dimensions and AUD symptoms. [ABSTRACT FROM AUTHOR]

Background: The assessment of a Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) life-time history of alcohol dependence (LTH-AD) has been found to be moderately reliable and substantially heritable. However, in studies of the heritability of LTH-AD, measurement error could not be discriminated from the true unique environmental effects. The aims of this study were to: (i) estimate the reliability of LTH-AD in a population based sample, (ii) identify characteristics of LTH-AD predicting a reliable diagnosis, (iii) investigate the heritability of LTH-AD as a function of diagnostic confidence, and (iv) to estimate the genetic and environmental influences on LTH-AD correcting for measurement error. Methods: An unselected sample of 4,203 male twins was interviewed twice approximately 1-year apart assessing DSM-IV LTH-AD over the same period of life. Logistic regression was used to identify clinical features that predict a reliable diagnosis LTH-AD. Genetic and environmental influences on reliable LTH-AD were examined using structural equation models. Results: Reliability of the diagnosis of LTH-AD was moderate (κ = 0.54) and was predicted by the number of AD symptoms, treatment seeking, duration of most severe episode, and a great deal of time spent to obtain, use, or recover from alcohol use (DSM-IV AD criterion #5). Using an index of caseness, heritability of LTH-AD increased as a function of diagnostic confidence. Accounting for errors of measurement in a multivariate twin model, the heritability of LTH-AD increased from 55 to 71%. Conclusions: Reliably diagnosed LTH-AD can be predicted by characteristics relevant to the disorder. LTH-AD appears to be a moderately reliable disorder of high heritability. [ABSTRACT FROM AUTHOR]

Background: Given the weight placed on retrospective reports of age at first drink in studies of later drinking-related outcomes, it is critical that its reliability be established and possible sources of systematic bias be identified. The overall aim of the current study is to explore the possibility that the estimated magnitude of association between early age at first drink and problem alcohol use may be inflated in studies using retrospectively reported age at alcohol use onset. Methods: The sample was comprised of 1,716 participants in the Missouri Adolescent Female Twin Study who reported an age at first drink in at least 2 waves of data collection (an average of 4 years apart). Difference in reported age at first drink at Time 2 versus Time 1 was categorized as 2 or more years younger, within 1 year (consistent), or 2 or more years older. The strength of the association between age at first drink and peak frequency of heavy episodic drinking (HED) at Time 1 was compared with that at Time 2. The association between reporting pattern and peak frequency of HED was also examined. Results: A strong association between age at first drink and HED was found for both reports, but it was significantly greater at Time 2. Just over one-third of participants had a 2 year or greater difference in reported age at first drink. The majority of inconsistent reporters gave an older age at Time 2 and individuals with this pattern of reporting engaged in HED less frequently than consistent reporters. Conclusions: The low rate of HED in individuals reporting an older age at first drink at Time 2 suggests that the upward shift in reported age at first drink among early initiates is most pronounced for light drinkers. Heavy drinkers may therefore be overrepresented among early onset users in retrospective studies, leading to inflated estimates of the association between early age at initiation and alcohol misuse. [ABSTRACT FROM AUTHOR]

Long-term functional brain effects of adolescent alcohol abuse remain uncertain, partially because of difficulties in distinguishing inherited deficits from neuronal effects of ethanol and by confounds associated with alcohol abuse, especially nicotine exposure. We conducted a longitudinal twin study to determine neurocognitive effects of adolescent alcohol abuse, as measured with the auditory event-related potential (ERP) component P3, a putative marker of genetic vulnerability to alcoholism. Twin pairs ( N = 177; 150 selected for intrapair concordance/discordance for alcohol-related problems at age 18½) were recruited from ongoing studies of twins born 1975-1979 in Finland. Alcohol and tobacco use were assessed with questionnaires at ages 16, 17, 18½, and ∼25, and by a structured psychiatric interview concurrent with the ERP testing at mean age 25.8. During ERP recordings, subjects were instructed to detect target tones within a train of frequent 'standards' and to ignore occasional 'novel' sounds. To distinguish familial factors from ethanol effects, ERP and self-reported alcohol use measures were incorporated into hierarchical multiple regression (HMR) analysis, and intrapair differences in ERP were associated with intra-pair differences in alcohol variables. Novel-sound P3 amplitude correlated negatively with self-reported alcohol use in both between- and within-family analyses. No similar effect was observed for target-tone P3. HMR results suggest that twins' similarity for novel-sound P3 amplitude is modulated by their alcohol use, and this effect of alcohol use is influenced by genetic factors. Our results, from a large sample of twins selected from a population-based registry for pairwise concordance/discordance for alcohol problems at 18½, demonstrate that adolescent alcohol abuse is associated with subtle neurophysiological changes in attention and orienting. The changes are reflected in decreased novel-sound P3 amplitude and may be modified by genetic factors. [ABSTRACT FROM AUTHOR]

The Rutgers Alcohol Problem Index (RAPI) is widely used to assess adolescent drinking-related problems. We asked how well RAPI, administered in late adolescence, predicts alcohol diagnoses at age 25 in a 7-year follow-up. At age 18, a population-based sample of Finnish twins completed RAPI by postal questionnaire; 597 (300 male) twins, from pairs discordant and concordant for age 18 RAPI scores, were interviewed at age 25 with the SSAGA, yielding DSM-IIIR diagnoses. Polychoric correlations between RAPI and alcohol diagnoses and symptoms, the area under the response operator characteristic (ROC) curve, and the odds ratio of outcome diagnosis per unit change in adolescent RAPI were analyzed. Twin pairs discordant for both adolescent RAPI and adult diagnoses permitted within-family replications for the full sample and separately by sex. Nearly half the interviewed twins met diagnostic criteria for alcohol dependency (46.2%) or abuse (1.5%). Age 18 RAPI scores significantly correlated with diagnoses (0.52) and symptom counts (0.55). ROC analysis found a 74% probability that adolescent RAPI scores will be higher among those with an alcohol diagnosis at age 25 than for those without. The odds ratio of outcome alcohol diagnosis per unit increase in adolescent 18 RAPI exceeded 10.0. Within-family comparisons of 117 twin pairs discordant for both age 18 RAPI and age 25 alcohol diagnoses replicated the between-family associations. In both between-family and within-family analyses, RAPI was more predictive of alcohol diagnoses among females. Our results offer evidence, including that from informative comparisons of co-twins discordant for both predictor and outcome, that RAPI scores in late adolescence robustly predict alcohol diagnoses in early adulthood. Accordingly, our results also provide new evidence that one pathway to problem drinking in early adulthood is a direct one from problem drinking in adolescence. [ABSTRACT FROM AUTHOR]

Although associations between drinking behavior and marital status are well documented, timing of marital transitions as a function of alcohol use or disorder has received limited empirical attention. We examine the relationship between lifetime history of alcohol dependence (AD) and timing and survival of first marriages in a sample of 3,575 female and 1,845 male adult Australian twins born mostly between 1940 and 1964. Survival analyses were conducted using Cox proportional hazards regression models. Results indicate moderate delays in marriage associated with AD for both women and men. Among ever-married respondents, AD was strongly predictive of early separation, with similar effects observed for women and men. Heritable sources of covariation were also documented. For women, genetic influences shared between early-onset AD and marital timing were found. Genetic influences shared between AD and marital survival were observed for women without regard to onset and for men with later-onset AD. Results confirm the importance of AD as a predictor of both timing and survival of first marriages, with genetic influences contributing to observed associations. [ABSTRACT FROM AUTHOR]

Excessive alcohol consumption contributes to significant morbidity and mortality. Heritable influences contribute to 50% of the variation in alcohol consumption, suggesting the important role of genes. We used data on a previously defined alcohol consumption factor score in a sample of 827 young women to investigate association with 1,014 single-nucleotide polymorphisms in genes related to addiction. Data were drawn from the Missouri Adolescent Female Twin Study (MOAFTS) with replication in the college drinking sample (CDS). Genotypic and phenotypic data were available on 827 MOAFTS and 100 CDS women of European-American ancestry. Data on 1,014 single-nucleotide polymorphisms (SNPs) across 130 genes related to addiction were utilized. Association was conducted in QTDT, which allows for identity-by-descent information to account accurately for twin status in the analysis. The total association variance components model was used, with specification of variance components for relatedness in MOAFTS. The top signals included clusters of SNPs in tryptophan hydroxylase 2 ( TPH2) (e.g., rs1386496, p = 0.0003) and dopa decarboxylase ( DDC) (e.g., rs3779084, p = 0.0008), genes that encode proteins responsible for serotonin synthesis. Additional polymorphisms in ADH1B, ADH1C, ADH7, and ADH1A1 were also associated at p < 0.05. The false discovery rate for the top signal ( p = 0.0003) was 0.15, suggesting nominal significance only. Replication was limited and noted for 2 SNPs in ADH1C. While no results survive the burden of multiple testing, nominal findings in TPH2 and DDC suggest the potential role of the serotonin synthesis pathway in alcohol consumption. [ABSTRACT FROM AUTHOR]

Alcohol use motives are closely associated with specific profiles of alcohol use and reflect a subjectively derived decisional framework based on a motivational style of responding. Adult twin studies typically estimate the heritability of alcohol use motives to be between 7 and 42%, although relatively little is known about genetic and environmental influences upon alcohol use motives in adolescence. Latent class analysis (LCA) models containing 1 through 5 classes were fitted to the data derived from 1,422 adolescent twin and siblings self-reported alcohol use motives. Using twin models, we estimated the genetic, shared, and nonshared environmental influences to the class membership data derived from the LCA. Four drinking motives classes were identified (family-oriented, social, enhancement/social, and coping/social). The coping/social and enhancement/social classes were differentiated from the social class on measures of depression, delinquency, and aggressive behavior. Analyses indicated that nonadditive genetic factors accounted for 76% of the variance in the coping/social motives class and additive genetic influences accounted for 66% of the variance in the social motives class. There was a moderate contribution of genetic factors and shared environmental factors influencing class membership of enhancement/social motivated drinkers (28 and 20% explained variance, respectively). Substantial shared environmental influences were revealed for membership of the family-oriented class (75%). Heritable influences may predispose individuals to drink to cope with negative affect, for social reasons, and to a lesser extent for enhancement. Familial environmental influences shape family-oriented motives for drinking in adolescents. [ABSTRACT FROM AUTHOR]

Alcohol and tobacco use often co-occur. Human and animal studies indicate that nicotine increases alcohol's rewarding effects and the motivation to consume it. The aims of this study were to examine whether the factorial architecture of self-reported motivations to consume alcohol differed between regular and nonregular cigarette smokers while taking into account the lifetime history of alcohol dependence and psychopathology, and to estimate the genetic and environmental influences on the motivations. Using data on 2,189 monozygotic and dizygotic female twins, we examined the factorial structure (item thresholds and factor loadings, means, and variances) of the items from the Drinking Motives Questionnaire (DMQ) in regular and nonregular smokers. Post hoc tests examined the association between the latent drinking motives factors and alcohol dependence in both groups. Twin models were fitted to the latent drinking motives factors, testing for variations in the magnitude of additive genetic, shared, and nonshared environmental influences between the groups. The 4 DMQ factors (social, conformity, coping, and enhancement) were recovered in both groups, and their measurement structure was consistent across the groups. Regular smokers reported higher levels of coping, enhancement, and social motives while nonregular smokers reported higher conformity motives. Alcohol dependence was associated with higher scores on all motives in both groups; however, in a regression analysis that included all of the motives as predictor variables, only coping was significantly related to alcohol dependence. While twin models revealed evidence for substantially greater genetic influences on enhancement ( h = 0.40), coping ( h = 0.35) and social ( h = 0.37) drinking motives in regular compared to nonregular smokers, the power to statistically distinguish the 2 groups was low. While the measurement structure of the drinking motive factors appears to be similar across regular and nonregular smokers, regular smokers report more motivation to drink for internal affect-related reasons and to obtain social reward. Of all the motives, coping was the most robust predictor of alcohol dependence in both the regular and the nonregular smokers. Further, genetic influences might play a larger role in drinking motives among regular smokers, which provides tentative evidence for latent genetic × smoking status interactions. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated that the heritability of alcohol-related phenotypes depends upon the social background in which it is measured (e.g., urbanicity, marital status, and religiosity). The aim of the current study was to identify whether religiosity moderated the genetic variance of problem alcohol use in men and women at two time points: adolescence and early adulthood. Method: Participants were 312 male MZ pairs, 379 female MZ pairs, 231 male DZ pairs, 235 female DZ pairs, and 275 opposite sex DZ pairs participating in the University of Colorado Center on Antisocial Drug Dependence. Religiosity was measured using the Value on Religion Scale ( Jessor and Jessor, 1977 ), and problem alcohol use was measured using the Composite International Diagnostic Interview–Substance Abuse Module ( Cottler et al., 1989 ). Data were analyzed using a model-fitting approach to the twin data. Results: In adolescence, genetic variance of problem alcohol use decreased significantly with increasing levels of religiosity in both men and women, whereas in early adulthood, religiosity did not moderate the genetic variance of problem alcohol use in either men or women. Conclusion: Religiosity appears to moderate the genetic effects on problem alcohol use during adolescence, but not during early adulthood. The reduced genetic variance for problem alcohol use in adolescence may be the consequence of greater social control in adolescence than in young adulthood. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Major depression and alcohol dependence co-occur within individuals and families to a higher than expected degree. This study investigated whether mood-related drinking motives mediate the association between major depression and alcohol dependence, and what the genetic and environmental bases are for this relationship. Methods: The sample included 5,181 individuals from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, aged 30 and older. Participants completed a clinical interview which assessed lifetime major depression, alcohol dependence, and mood-related drinking motives. Results: Mood-related drinking motives significantly explained the depression-alcohol dependence relationship at both the phenotypic and familial levels. Results from twin analyses indicated that for both males and females, the familial factors underlying mood-related drinking motives accounted for virtually all of the familial variance that overlaps between depression and alcohol dependence. Conclusions: The results are consistent with an indirect role for mood-related drinking motives in the etiology of depression and alcohol dependence, and suggest that mood-related drinking motives may be a useful index of vulnerability for these conditions. [ABSTRACT FROM AUTHOR]

Background: Alcohol dependence (AD) is among the most common psychiatric disorders, and impacts the health and well-being of problem drinkers, their family members, and society as a whole. Although previous research has consistently indicated that genetic factors contribute to variance in risk for AD, little attention has been paid to nonrandom mating for AD. When assortative mating occurs for a heritable trait, spouses are genetically correlated and offspring are at increased risk of receiving high-risk genes from both parents. The primary goal of the present analyses is to test hypotheses about the source(s) and magnitude of spousal associations for AD using a twin-spouse design. Methods: DSM-IV AD (without the clustering criterion) was assessed via telephone interview for 5,974 twin members of an older cohort of the Australian Twin Register (born 1902–1964) and 3,814 spouses of the twins. Quantitative genetic modeling was used to determine the extent to which variability in risk for AD was influenced by genetic factors, the extent of spousal association for AD, and whether the association was attributable to assortative mating, reciprocal spousal interaction, or both processes. Results: Genetic factors explained 49% of the variance in risk for AD. There was no evidence of gender differences in the spousal interaction effect, the degree of rater bias, or the association between the twin's report of spouse AD and the spouse's AD phenotype. Either the assortative mating parameter or the spousal interaction parameter could be removed from the model without a significant decrement in fit, but both could not be dropped simultaneously, suggesting a lack of power to differentiate between these 2 causes of spousal correlation. When both effects were included in the model, the spousal correlation was 0.29, the assortative mating coefficient was 0.45 (i.e., “like marries like”), and the reciprocal spousal interaction coefficient was −0.10 (i.e., after controlling for assortative mating, the additional impact of spousal interactions is slightly protective). Conclusions: These analyses provide evidence of significant spousal associations for AD, with assortative mating increasing spouse similarity and spousal interaction effects decreasing it after controlling for assortative mating. Although the genetic impact is modest, assortative mating results in an increased proportion of offspring exposed to 2 alcoholic parents and the associated detrimental environmental sequelae, and increases the likelihood of offspring inheriting high-risk genes from both parents. [ABSTRACT FROM AUTHOR]

Background: Hormonal responses to alcohol have been reported to differ in subjects with and without a family history of alcoholism which suggests that alcohol-induced hormonal changes might be used to identify individuals who are at elevated genetic risk for developing alcoholism. However, before a biological response can be used as a marker of genetic risk for disease, it must first be demonstrated that the response is, in fact, heritable. The present study was designed to determine whether hormonal responses to alcohol are heritable. Methods: The adrenocorticotropic hormone (ACTH), beta-endorphin (β-E), cortisol (CORT), and prolactin (PRL) responses to alcohol were examined in male and female identical (monozygotic or MZ) and fraternal (dizygotic or DZ) twin pairs. Male subjects consumed 0.35g ethanol/kg body weight (BW) and female consumed 0.325 g ethanol/kg BW in each of two alcohol drinking sessions administered 1 hr apar (total dose of 0.7 g/kg BW in males and 0.65 g/kg BW in females). Plasma hormone content was analyzed in samples collected before (resting conditions) and at 15, 60, 75, 120, 180, and 240 min after onset of drinking. Hormonal responses to alcohol were examined with twin analyses using the TWINAN90 program. A separate analysis was performed for each of the four hormones. A subset of subjects from each zygosity was seen on two separate occasions to establish retest reliability. Heritability of hormonal responses to alcohol was estimated using the intraclass correlation approach before and after removing the contribution of covariates that have the potential of influencing the plasma levels of these hormones. Results: Resting plasma levels of all four hormones were within the expected range, and the β-E, ACTH, and PRL responses to the alcohol challenge evidenced good test-retest reliability. Of the four hormones examined, the only one that showed significant heritability after alcohol drinking was β-E. Heritability estimates were not altered for any of the four hormones after removal of the variance contributed by covariates, such as gender and age. Conclusions: Taken together with other recent findings, the results suggest that the β-E response to alcohol may represent a new biomarker that can be used to identify individuals who are at elevated genetic risk for developing alcoholism. [ABSTRACT FROM AUTHOR]

The author comments on a study by KS Kendler and colleagues which identified a latticework of risk and protective factors underlying liability to alcohol problems (AP) in opposite-sex siblings. Topics discussed include the study's 2 innovative features including the leverage of the genetic and familial matching afforded by dizygotic opposite-sex sibling pairs and the developmental contributors to interface with each other, estimating direct and indirect paths.

Background: There are substantial sex differences in all levels of alcohol involvement among U.S. adults. The goal of this study was to test whether the magnitude and sources of genetic and environmental influences on liability for alcohol abuse and dependence differ for men and women. Methods: Structured personal interviews were used to assess DSM-III-R- and DSM-IV-defined alcohol abuse and dependence among 5091 male and 4168 female twins (including 1546 identical, 1128 same-sex fraternal, and 1423 opposite-sex pairs) born in Virginia between 1934 and 1974. Twin correlations were analyzed using structural equation modeling. Results: The magnitude of twin-pair resemblance was similar across several definitions of alcoholism and was substantially higher among identical than fraternal pairs. The proportion of population variation in liability attributed to genetic factors was substantial among both women (55-66%) and men (51-56%), and we found little evidence of a role of environmental factors shared by family members. In all definitions studied, we could reject a model that the genetic sources of liability in the two sexes overlap completely. Conclusion: In this first population-based study of alcoholism among male and female twins from the U.S., we found that genetic factors play a major role in the development of alcoholism in both sexes, that the magnitudes of genetic influence were equally high for men and women, and that the genetic sources of vulnerability are partially, but not completely, overlapping in men and women. [ABSTRACT FROM AUTHOR]

There is consistent evidence from twin and adoption studies implicating genetic factors in the etiology of alcoholism, yet few studies have examined the role of genetic influences on individual symptoms of alcoholism. In a previous study of 113 male twins, Johnson et al. (1996a) identified 7 alcoholism symptoms that were more 'genetic' and 14 that were more 'environmental' (that is, non-genetic) in their etiology by examining symptom concordances among monozygotic and dizygotic twin pairs. The present study represents an attempt to replicate the results of this previous study and extend them by estimating the contribution of genetic factors to the variation in liability for different alcoholism symptoms. Subjects were 3356 male twin pairs from the Vietnam Era Twin Registry. Lifetime histories of alcoholism symptoms were assessed by a structured psychiatric telephone interview. The results of the previous study were not replicated. The correlations between symptom classifications as genetic and non-genetic in the present and previous study were nonsignificant and ranged from -0.27 to 0.11. However, within the present study the correlation between symptom classifications as genetic and non-genetic was statistically significant across random split-half subsamples ( r= 0.59); nine alcoholism symptoms were consistently classified as genetic and six symptoms as non-genetic in their etiology. Model-fitting analyses applied to different alcoholism symptoms yielded heritability estimates ranging from 0.03 to 0.53 with broad and overlapping confidence intervals around these estimates, ranging from 0.00 to 0.65. The results of this study highlight the difficulty of identifying more or less heritable phenotypes in twin research, and suggest that it may not be possible to identify specific alcoholism symptoms that are more genetic in their etiology than others. Nevertheless, there appears to be potentially important variation in the relative magnitude of genetic influences for individual alcoholism symptoms, and exploring these differences may lead to further insights into the nosology and etiology of alcohol-related problems. [ABSTRACT FROM AUTHOR]

A two-dose alcohol challenge protocol was used to study genetic influences on the acute adaptation of the EEG to alcohol in 53 monozygotic and 38 same-sex dizygotic Caucasian twin pairs averaging 30 years of age. Equal doses of alcohol were administered at 10:00 and 11:00 AM, yielding mean peak breath alcohol concentrations of 0.057% and 0.099%, respectively. Eyes-closed, resting EEG was recorded four times: at baseline; on the ascending limb of the overall experiment at a breath alcohol concentration (BrAC) near 0.06%; on the descending limb at a BrAC near the value when the subject's EEG was obtained on the ascending limb; and, finally, when the BrAC fell to 0.02%. Genetic analyses of log-transformed values of total spectral power (L10TSP) and spectral band power (L10SBP) were performed on EEG spectra averaged across all 17 scalp lead locations. After adjusting for body weight, a significant fraction of population variance in L10TSP was attributable to genetic influence: H2 values for TSP were 0.73, 0.72, and 0.73 at the three postalcohol EEG recordings, respectively. Similar findings pertained to each L10SBP at each postalcohol recording, except for the delta band. The change in postethanol EEG power was examined for evidence that genes influence acute adaptations in brain function. Descending-minus-ascending limb L10TSP was normalized by the individual's ascending limb L10TSP to minimize nonalcohol-related effects that can influence both measurements. Earlier analyses of the same sample's initial EEG response to alcohol noted a substantial increase in the ascending limb EEG power, compared with baseline. Thus, positive values of the postethanol change denote a progression away from baseline attributable to acute sensitization to alcohol; negative values signify a return toward baseline values suggesting acute tolerance to alcohol. Genetic analysis of the normalized difference in L10TSP had a highly significant H2 value of 0.70, indicating that both acute tolerance and acute sensitization to alcohol may represent adaptations reflecting substantial heritable influence. Slightly smaller, but significant values of H2 for the normalized difference in L10SPB were observed for delta, alpha-slow and beta-slow frequency bands. In contrast, H2 for the differences between the final and ascending limb EEG power were not significant, except for the theta band. Thus, heritable drowsiness may have contributed to detection of genetic influences on acute adaptation, but represent a potential confound only in the theta band. [ABSTRACT FROM AUTHOR]