Using a developmental perspective to examine the moderating effects of marriage on heavy episodic drinking in a young adult sample enriched for risk.

Many studies demonstrate that marriage protects against risky alcohol use and moderates genetic influences on alcohol outcomes; however, previous work has not considered these effects from a developmental perspective or in high-risk individuals. These represent important gaps, as it cannot be assumed that marriage has uniform effects across development or in high-risk samples. We took a longitudinal developmental approach to examine whether marital status was associated with heavy episodic drinking (HED), and whether marital status moderated polygenic influences on HED. Our sample included 937 individuals (53.25% female) from the Collaborative Study on the Genetics of Alcoholism who reported their HED and marital status biennially between the ages of 21 and 25. Polygenic risk scores (PRS) were derived from a genome-wide association study of alcohol consumption. Marital status was not associated with HED; however, we observed pathogenic gene-by-environment effects that changed across young adulthood. Among those who married young (age 21), individuals with higher PRS reported more HED; however, these effects decayed over time. The same pattern was found in supplementary analyses using parental history of alcohol use disorder as the index of genetic liability. Our findings indicate that early marriage may exacerbate risk for those with higher polygenic load.

Using Patterns of Genetic Association to Elucidate Shared Genetic Etiologies Across Psychiatric Disorders.

Twin studies indicate that latent genetic factors overlap across comorbid psychiatric disorders. In this study, we used a novel approach to elucidate shared genetic factors across psychiatric outcomes by clustering single nucleotide polymorphisms based on their genome-wide association patterns. We applied latent profile analysis (LPA) to p-values resulting from genome-wide association studies across three phenotypes: symptom counts of alcohol dependence (AD), antisocial personality disorder (ASP), and major depression (MD), using the European-American case-control genome-wide association study subsample of the collaborative study on the genetics of alcoholism (N = 1399). In the 3-class model, classes were characterized by overall low associations (85.6% of SNPs), relatively stronger association only with MD (6.8%), and stronger associations with AD and ASP but not with MD (7.6%), respectively. These results parallel the genetic factor structure identified in twin studies. The findings suggest that applying LPA to association results across multiple disorders may be a promising approach to identify the specific genetic etiologies underlying shared genetic variance.

The Impact of Peer Substance Use and Polygenic Risk on Trajectories of Heavy Episodic Drinking Across Adolescence and Emerging Adulthood.

BACKGROUND: Heavy episodic drinking is developmentally normative among adolescents and young adults, but is linked to adverse consequences in later life, such as drug and alcohol dependence. Genetic and peer influences are robust predictors of heavy episodic drinking in youth, but little is known about the interplay between polygenic risk and peer influences as they impact developmental patterns of heavy episodic drinking. METHODS: Data were from a multisite prospective study of alcohol use among adolescents and young adults with genome-wide association data (n = 412). Generalized linear mixed models were used to characterize the initial status and slopes of heavy episodic drinking between age 15 and 28. Polygenic risk scores (PRS) were derived from a separate genome-wide association study for alcohol dependence and examined for their interaction with substance use among the adolescents' closest friends in predicting the initial status and slopes of heavy episodic drinking. RESULTS: Close friend substance use was a robust predictor of adolescent heavy episodic drinking, even after controlling for parental knowledge and peer substance use in the school. PRS were predictive of the initial status and early patterns of heavy episodic drinking in males, but not in females. No interaction was detected between PRS and close friend substance use for heavy episodic drinking trajectories in either males or females. CONCLUSIONS: Although substance use among close friends and genetic influences play an important role in predicting heavy episodic drinking trajectories, particularly during the late adolescent to early adult years, we found no evidence of interaction between these influences after controlling for other social processes, such as parental knowledge and broader substance use among other peers outside of close friends. The use of longitudinal models and accounting for multiple social influences may be crucial for future studies focused on uncovering gene-environment interplay. Clinical implications are also discussed.

Gender and Direction of Effect of Alcohol Problems and Internalizing Symptoms in a Longitudinal Sample of College Students.

BACKGROUND: Alcohol problems and internalizing symptoms are consistently found to be associated but how they relate to each other is unclear. OBJECTIVE: The present study aimed to address limitations in the literature of comorbidity of alcohol problems and internalizing symptoms by investigating the direction of effect between the phenotypes and possible gender differences in college students. METHOD: We utilized data from a large longitudinal study of college students from the United States (N = 2607). Three waves of questionnaire-based data were collected over the first two years of college (in 2011-2013). Cross-lagged models were applied to examine the possible direction of effect of internalizing symptoms and alcohol problems. Possible effects of gender were investigated using multigroup modeling. RESULTS: There were significant correlations between alcohol problems and internalizing symptoms. A direction of effect was found between alcohol problems and internalizing symptoms but differed between genders. A unidirectional relationship varying with age was identified for males where alcohol problems initially predicted internalizing symptoms followed by internalizing symptoms predicting alcohol problems. For females, a unidirectional relationship existed wherein alcohol problems predicted internalizing symptoms. Conclusions/Importance: We conclude that the relationship between alcohol problems and internalizing symptoms is complex and differ between genders. In males, both phenotypes are predictive of each other, while in females the relationship is driven by alcohol problems. Importantly, our study examines a population-based sample, revealing that the observed relationships between alcohol problems and internalizing symptoms are not limited to individuals with clinically diagnosed mental health or substance use problems.

Level of response to alcohol as a factor for targeted prevention in college students.

BACKGROUND: Heavy alcohol consumption and alcohol problems among college students are widespread and associated with negative outcomes for individuals and communities. Although current methods for prevention and intervention programming have some demonstrated efficacy, heavy drinking remains a problem. A previous pilot study and a recent large-scale evaluation (Schuckit et al., , ) found that a tailored prevention program based on a risk factor for heavy drinking, low level of response (low LR) to alcohol, was more effective at reducing heavy drinking than a state-of-the-art (SOTA) standard prevention program for individuals with the low LR risk factor. METHODS: This study enrolled 231 first-semester college freshmen with either high or low LR into the same level of response-based (LRB) or SOTA online prevention programs as in the previous reports (consisting of 4 weeks of video modules), as well as a group of matched controls not receiving alcohol prevention, and compared changes in alcohol use between these groups across a 6-month period. RESULTS: Individuals in alcohol prevention programs had a greater reduction in maximum drinks per occasion and alcohol use disorder symptoms than controls. There was limited evidence for interactions between LR and prevention group in predicting change in alcohol use behaviors; only among participants with strict adherence to the program was there an interaction between LR and program in predicting maximum drinks per occasion. However, overall, low LR individuals showed greater decreases in drinking behaviors, especially risky behaviors (e.g., maximum drinks, frequency of heavy drinking) than high LR individuals. CONCLUSIONS: These results indicate that prevention programs, including brief and relatively inexpensive web-based programs, may be effective for persons at highest risk for heavier drinking, such as those with a low LR. Tailored programs may provide incremental benefits under some conditions. Long-term follow-ups and further investigations of tailored prevention programs based on other risk factors are needed.

The predictive power of family history measures of alcohol and drug problems and internalizing disorders in a college population.

A family history (FH) of psychiatric and substance use problems is a potent risk factor for common internalizing and externalizing disorders. In a large web-based assessment of mental health in college students, we developed a brief set of screening questions for a FH of alcohol problems (AP), drug problems (DP) and depression-anxiety in four classes of relatives (father, mother, aunts/uncles/grandparents, and siblings) as reported by the student. Positive reports of a history of AP, DP, and depression-anxiety were substantially correlated within relatives. These FH measures predicted in the student, in an expected pattern, dimensions of personality and impulsivity, alcohol consumption and problems, smoking and nicotine dependence, use of illicit drugs, and symptoms of depression and anxiety. Using the mean score from the four classes of relatives was more predictive than using a familial/sporadic dichotomy. Interactions were seen between the FH of AP, DP, and depression-anxiety and peer deviance in predicting symptoms of alcohol and tobacco dependence. As the students aged, the FH of AP became a stronger predictor of alcohol problems. While we cannot directly assess the validity of these FH reports, the pattern of findings suggest that our brief screening items were able to assess, with some accuracy, the FH of substance misuse and internalizing psychiatric disorders in relatives. If correct, these measures can play an important role in the creation of developmental etiologic models for substance and internalizing psychiatric disorders which constitute one of the central goals of the overall project.

Childhood internalizing symptoms are negatively associated with early adolescent alcohol use.

BACKGROUND: The relationship between childhood internalizing problems and early adolescent alcohol use has been infrequently explored and remains unclear. METHODS: We employed growth mixture modeling of internalizing symptoms for a large, population-based sample of U.K. children (the Avon Longitudinal Study of Parents and Children Cohort) to identify trajectories of childhood internalizing symptoms from age 4 through age 11.5. We then examined the relationship between membership in each trajectory and alcohol use in early adolescence (reported at age 13.8). RESULTS: Overall, children experiencing elevated levels of internalizing symptoms were less likely to use alcohol in early adolescence. This finding held true across all internalizing trajectories; that is, those exhibiting increasing levels of internalizing symptoms over time, and those whose symptoms desisted over time, were both less likely to use alcohol than their peers who did not exhibit internalizing problems. CONCLUSIONS: We conclude that childhood internalizing symptoms, unlike adolescent symptoms, are negatively associated with early adolescent alcohol experimentation. Additional studies are warranted to follow up on our preliminary evidence that symptoms of phobia and separation anxiety drive this effect.

Directional relationships between alcohol use and antisocial behavior across adolescence.

BACKGROUND: The co-occurrence of alcohol use and antisocial behavior is well established, but different hypotheses exist regarding the direction of effects between the 2 behaviors. We used longitudinal data to examine the directional relationship between the 2 behaviors across adolescence. METHODS: A cross-lagged model was applied to longitudinal data from the Avon Longitudinal Study of Parents and Children. The sample used in the present study consisted of 4,354 females and 3,984 males. Alcohol use and antisocial behavior were measured with multiple items collected at 12, 13, 15, and 17 years of age. RESULTS: Both alcohol use and antisocial behavior were highly stable, as evidenced by highly significant autoregressive paths. Regarding the cross-lagged paths, neither behavior was predictive of the other during early adolescence (between ages 12 and 13). During mid-to late adolescence (from ages 13 to 17), antisocial behavior was predictive of subsequent alcohol use. Alcohol use was predictive of antisocial behavior in late adolescence (between ages 15 and 17), although this relationship was mainly driven by males and was not significant in the female subgroup. CONCLUSIONS: The result generally supported the direction from antisocial behavior to alcohol use, especially during mid- to late adolescence. However, there was also a suggestion that the direction of relationship between the 2 behaviors changes across adolescence. The results highlight the importance of considering developmental stages to understand the directional relationships between the 2 behaviors.

Genetic influences on alcohol use across stages of development: GABRA2 and longitudinal trajectories of drunkenness from adolescence to young adulthood.

Longitudinal analyses allow us to understand how genetic risk unfolds across development, in a way that is not possible with cross-sectional analyses of individuals at different ages. This has received little attention in genetic association analyses. In this study, we test for genetic effects of GABRA2, a gene previously associated with alcohol dependence, on trajectories of drunkenness from age 14 to 25. We use data from 1070 individuals who participated in the prospective sample of the Collaborative Study on the Genetics of Alcoholism, in order to better understand the unfolding of genetic risk across development. Piecewise linear growth models were fit to model the influence of genotype on rate of increase in drunkenness from early adolescence to young adulthood (14-18 years), the change in drunkenness during the transition to adulthood (18-19 years) and the rate of change in drunkenness across young adulthood (≥ 19 years). Variation in GABRA2 was associated with an increase in drunkenness that occurred at the transition between adolescence and adulthood. The genotypic effect was more pronounced in females. These analyses illustrate the importance of longitudinal data to characterize how genetic effects unfold across development. The findings suggest that transitions across important developmental periods may alter the relative importance of genetic effects on patterns of alcohol use. The findings also suggest the importance of considering gender when evaluating genetic effects on drinking patterns in males and females.

Carotid Artery Plaque Identification and Display System (MRI-CAPIDS) Using Opensource Tools.

Magnetic resonance imaging (MRI) represents one modality in atherosclerosis risk assessment, by permitting the classification of carotid plaques into either high- or low-risk lesions. Although MRI is generally used for observing the impact of atherosclerosis on vessel lumens, it can also show both the size and composition of itself, as well as plaque information, thereby providing information beyond that of simple stenosis. Software systems are a valuable aid in carotid artery stenosis assessment wherein commercial software is readily available but is not accessible to all practitioners because of its often high cost. This study focuses on the development of a software system designed entirely for registration, marking, and 3D visualization of the wall and lumen, using freely available open-source tools and libraries. It was designed to be free from "feature bloat" and avoid "feature-creep." The image loading and display module of the modified QDCM library was improved by a minimum of 10,000%. A Bezier function was used in order to smoothen the curve of the polygon (referring to the shape formed by the marked points) by interpolating additional points between the marked points. This smoother curve led to a smoother 3D view of the lumen and wall.

Decomposing group differences of latent means of ordered categorical variables within a genetic factor model.

A genetic factor model is introduced for decomposition of group differences of the means of phenotypic behavior as well as individual differences when the research variables under consideration are ordered categorical. The model employs the general Genetic Factor Model proposed by Neale and Cardon (Methodology for genetic studies of twins and families, 1992) and, more specifically, the extension proposed by Dolan et al. (Behav Genet 22: 319-335, 1992) which enables decomposition of group differences of the means associated with genetic and environmental factors. Using a latent response variable (LRV) formulation (Muthén and Asparouhov, Latent variable analysis with categorical outcomes: multiple-group and growth modeling in Mplus. Mplus web notes: No. 4, Version 5, 2002), proportional differences of response categories between groups are modeled within the genetic factor model in terms of the distributional differences of latent response variables assumed to underlie the observed ordered categorical variables. Use of the proposed model is illustrated using a measure of conservatism in the data collected from the Australian Twin Registry.

Positive and negative reinforcement are differentially associated with alcohol consumption as a function of alcohol dependence.

A multistage model of drug addiction in which individuals' motivations for use change as they develop problems is widely accepted; however, the evidence for this model comes mostly from animal work and cross-sectional studies. We used longitudinal data to test whether positive and negative reinforcement associated with alcohol consumption differed as a function of alcohol dependence (AD). Specifically, we tested whether (a) positive reinforcement is more strongly associated with alcohol consumption than is negative reinforcement among individuals without AD, (b) negative reinforcement is more strongly associated with AD than is positive reinforcement, and (c) in the presence of AD, the association between positive reinforcement and alcohol consumption becomes weaker, whereas the association with negative reinforcement becomes stronger. We included assessments between Ages 18 and 30 years from participants who indicated they ever had a drink (N = 2,556; 51.6% female) from the Collaborative Study on the Genetics of Alcoholism Prospective Study. Results from generalized estimating equations indicated that positive, but not negative, reinforcement was associated with alcohol consumption among individuals without AD. Both positive and negative reinforcement were associated with AD, but the association was stronger with negative reinforcement. Results from the multilevel growth model indicated that the association between negative reinforcement and alcohol consumption became stronger with the presence of AD, whereas the association between positive reinforcement and alcohol consumption did not differ as a function of AD. We provide empirical evidence that positive and negative reinforcement are differentially associated with alcohol consumption as a function of AD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Post-GWAS in Psychiatric Genetics: A Developmental Perspective on the "Other" Next Steps.

As psychiatric genetics enters an era where gene identification is finally yielding robust, replicable genetic associations and polygenic risk scores, it is important to consider next steps and delineate how that knowledge will be applied to ultimately ameliorate suffering associated with substance use and psychiatric disorders. Much of the post-genome-wide association study discussion has focused on the potential of genetic information to elucidate the underlying biology and use this information for the development of more effective pharmaceutical treatments. In this review we focus on additional areas of research that should follow gene identification. By taking genetic findings into longitudinal, developmental studies, we can map the pathways by which genetic risk manifests across development, elucidating the early behavioral manifestations of risk, and studying how various environments and interventions moderate that risk across developmental stages. The delineation of risk across development will advance our understanding of mechanism, sex differences and risk and resilience processes in different racial/ethnic groups. Here, we review how the extant twin study literature can be used to guide these efforts. Together, these new lines of research will enable us to develop more informed, tailored prevention and intervention efforts.

Genes, Environments, and Sex Differences in Alcohol Research.

OBJECTIVE: The study of sex differences has been identified as one way to enhance scientific reproducibility, and the National Institutes of Health (NIH) have implemented a new policy to encourage the explicit examination of sex differences. Our goal here is to address sex differences in behavioral genetic research on alcohol outcomes. METHOD: We review sex differences for alcohol outcomes and whether the source and magnitude of genetic influences on alcohol consumption and alcohol use disorder (AUD) are the same across sexes; describe common research designs for studying sex-specific gene-by-environment interaction (G × E) effects; and discuss the role of statistical power and theory when testing sex-specific genetic effects. RESULTS: There are robust sex differences for many alcohol outcomes. The weight of evidence suggests that the source and magnitude of genetic influences on alcohol consumption and AUD are the same across sexes. Whether there are sex-specific G × E effects has received less attention to date. CONCLUSIONS: The new NIH policy necessitates a systematic approach for studying sex-specific genetic effects in alcohol research. Researchers are encouraged to report power for tests of these effects and to use theory to develop testable hypotheses, especially for studies of G × E.

Longitudinal investigation of interpersonal trauma exposure and alcohol use trajectories.

BACKGROUND: The current longitudinal study examined associations between interpersonal potentially traumatic events (PTEs; i.e., sexual or physical assault) and changes in alcohol consumption among incoming college students. METHODS: 1197 students (68% female) participating in a university-wide research study were included in analyses. Assessments were administered at three time-points and included measures of alcohol use, PTEs (Life Events Checklist), and a screener for possible PTSD symptoms (abbreviated Primary Care PTSD Screen). Linear growth curve models were fit to the three repeated measures of alcohol quantity and frequency to determine the role of pre-college and college-onset interpersonal PTEs and possible PTSD symptoms on patterns of alcohol use. RESULTS: Pre-college interpersonal PTE was associated with greater baseline alcohol use for female but not male students. College-onset interpersonal PTE predicted greater alcohol use at concurrent and future assessments for women but not men, beyond the effects of pre-college PTE. Pre-college possible PTSD symptoms did not predict baseline or change in alcohol use. CONCLUSIONS: There may be a stronger and longer-lasting impact of interpersonal PTE for college women compared to men on alcohol phenotypes, although replication in studies oversampling men endorsing interpersonal PTE is needed.

The role of romantic relationship status in pathways of risk for emerging adult alcohol use.

Dating several people in emerging adulthood has been associated with higher alcohol use compared with being single or being in an exclusive relationship. As a follow-up to that report, we examined whether romantic relationship status is part of a pathway of risk between antecedent alcohol use risk factors and subsequent alcohol outcomes. Participants were 4,410 emerging adults assessed at 2 time-points during their first year of college. We found that a parental history of alcohol problems was indirectly related to dating several people via 2 modestly correlated pathways. The first pathway was through conduct problems. The second pathway was through positive urgency (i.e., a positive emotion-based predisposition to rash action). In turn, dating several people was associated with higher alcohol use. Our results suggest that these familial and individual-level alcohol risk factors are related to emerging adults' selection into subsequent romantic relationship experiences that are associated with higher alcohol use. These findings have implications for how romantic relationship experiences may fit into developmental models of the etiology of alcohol use. (PsycINFO Database Record

Predicting Tobacco Use across the First Year of College.

OBJECTIVE: The purpose of this study was to assess patterns of tobacco use across the first year of college, transitions in use, and associated predictors. METHODS: The frequency of tobacco use (cigarettes, cigars, smokeless tobacco, and hookah) during the fall and spring of 4073 college students' first year at college were used as indicators in latent class (LCA) and latent transition analyses (LTA). RESULTS: The LCA yielded 3 classes that represent levels of use frequency and not specific tobacco product classes: non-using, experimenting, and frequent using. The LTA results demonstrate stability in class membership from fall to spring. The most common transition was for the fall experimenters to transition out of experimentation. A series of demographic, environmental, and intrapersonal predictors were found to influence both fall class membership, and transitions from fall to spring. CONCLUSIONS: Students are likely to use multiple alternative tobacco products along with cigarettes. Their frequency of use of these products is fairly stable across the first year of college. Predictors reflecting experiences during the first year of college had the greatest impact on college tobacco use, demonstrating the importance of the college experience on young adult tobacco use.

Patterns of Substance Use Across the First Year of College and Associated Risk Factors.

Starting college is a major life transition. This study aims to characterize patterns of substance use across a variety of substances across the first year of college and identify associated factors. We used data from the first cohort (N = 2056, 1240 females) of the "Spit for Science" sample, a study of incoming freshmen at a large urban university. Latent transition analysis was applied to alcohol, tobacco, cannabis, and other illicit drug uses measured at the beginning of the fall semester and midway through the spring semester. Covariates across multiple domains - including personality, drinking motivations and expectancy, high school delinquency, peer deviance, stressful events, and symptoms of depression and anxiety - were included to predict the patterns of substance use and transitions between patterns across the first year. At both the fall and spring semesters, we identified three subgroups of participants with patterns of substance use characterized as: (1) use of all four substances; (2) alcohol, tobacco, and cannabis use; and (3) overall low substance use. Patterns of substance use were highly stable across the first year of college: most students maintained their class membership from fall to spring, with just 7% of participants in the initial low substance users transitioning to spring alcohol, tobacco, and cannabis users. Most of the included covariates were predictive of the initial pattern of use, but covariates related to experiences across the first year of college were more predictive of the transition from the low to alcohol, tobacco, and cannabis user groups. Our results suggest that while there is an overall increase in alcohol use across all students, college students largely maintain their patterns of substance use across the first year. Risk factors experienced during the first year may be effective targets for preventing increases in substance use.

Genetic overlap between personality and risk for disordered gambling: evidence from a national community-based Australian twin study.

Using data from a large Australian twin sample we examined the extent to which genetic variation in the Big Three personality dimensions (positive emotionality, negative emotionality, and constraint) and their lower-order components explained genetic variation in the risk for disordered gambling (DG) among men and women. Genetic influences contributing to individual differences in normal-range personality traits explained over 40% of the genetic risk for DG, with a larger contribution among women than among men. The largest and most robust contributions came from the higher-order personality dimension of negative emotionality and its two lower-order dimensions of alienation and aggression. Surprisingly, low self-control was associated with the genetic risk for DG only among women, and risk-taking/sensation-seeking did not explain genetic risk for DG in either sex. The results of this study have implications for the causes of comorbidity between DG and other psychiatric disorders, the search for genes associated with DG risk, and the possibility of sex differences in the etiology of DG. Using a broad-band inventory of personality supports the conclusion that there probably is a substantial proportion of genetic variation in DG that cannot be explained by individual differences in personality.