Drinking Patterns Across Spring, Summer, and Fall in 462 University Students.

BACKGROUND: Student heavy drinking and associated problems are common at most universities and fluctuate throughout the calendar year, with marked increases during celebrations. Most studies of student drinking are limited to the academic year itself, and relatively few focus specifically on special heavy drinking events. Even fewer studies include drinking during summer break and subsequent school return. METHODS: In the context of an experimental protocol, beginning in January 2014, alcohol-related characteristics were evaluated 8 times over 55 weeks for 462 college freshmen, including periods that incorporated a campus festival, summer, and school return. Baseline predictors of drinking quantities over time included demography, substance use patterns, as well as environmental and attitudinal characteristics. Product-moment correlations evaluated relationships between baseline characteristics and subsequent quantities, and simultaneous entry regression analyses evaluated which characteristics most robustly predicted usual and maximum drinks over time. RESULTS: Maximum drinks per occasion increased 18% from the early spring (4/8/14 to 5/6/14) to the campus festival period (5/7/14 to 6/3/14), decreased 29% in the summer (7/8/14 to 8/5/14), and increased 31% on school return (10/7/14 to 11/4/14). The most robust predictors of higher quantities in regression analyses included items from each of the 3 major domains with the most consistent results seen for most baseline alcohol-related items and descriptive drinking norms (R(2) = 0.20 to 0.31). CONCLUSIONS: These data demonstrate important changes in students' drinking during the calendar year, including expected large increases during the month of a 1-day festival, large decreases over the summer, and resumption of relatively high quantities upon return to school.

The Low Level of Response to Alcohol-Based Heavy Drinking Prevention Program: One-Year Follow-Up.

OBJECTIVE: Heavy drinking is common on college campuses, with a marked increase from high school to freshman year. Programs addressing heavy campus drinking often personalize prevention protocols to fit a student's demography and prior drinking characteristics. Few efforts have individualized approaches to address a person's vulnerability through his or her low level of response (low LR) to alcohol. METHOD: This article describes the recently completed 55-week outcome in drinking quantities and problems for the >90% of 500 participants in a prevention program at a U.S. university (62% female, mean age = 18 years) who completed a 4-week series of 50-minute videos delivered via the Internet. We evaluated whether, for low LRs, participation in an educational approach that focused on a low LR (the LR-based [LRB] condition) was associated with better outcomes than a state-of-the-art (SOTA) general education or with a no-intervention control condition. RESULTS: Using a mixed-design analysis of variance and focusing on the most closely ethnically matched high and low LR pairs, students with low LRs in the LRB condition demonstrated the greatest decreases in usual and maximum drinks over the 55 weeks, especially when compared with closely ethnically matched students with high LRs. Low LR controls showed the highest drinking values over time. CONCLUSIONS: This study underscores the potential importance of targeting a person's specific preexisting vulnerability toward heavy drinking when he or she enters college. The approach can be used in a relatively inexpensive protocol of video education sessions delivered via the Internet.

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 impact of focusing a program to prevent heavier drinking on a pre-existing phenotype, the low level of response to alcohol.

BACKGROUND: Heavy drinking is common during transitions from high school to college. Optimal programs for diminishing risks for high alcohol consumption often tailor the approach to the specific needs of students. This study describes the results of an Internet-based prevention protocol that tailors the information to the risk associated with a pre-existing phenotype, the Low level of Response (Low LR) to alcohol. METHODS: Using stratified random assignment, 454 freshmen with Low and High LR values were assigned to 2 education groups (LR-based where all examples were given the context of the Low LR model of heavy drinking or a State Of The Art (SOTA) Group where the same lessons were taught but without an emphasis on LR) or a no-intervention Control Group. Individuals in the 2 education groups viewed 50-minute online videos once per week for 4 weeks. Changes in drinking patterns were assessed at Baseline, 4 weeks, and 8 weeks using a 2 (LR status) by 3 (education group) by 3 (time points) analysis of variance, with additional tests for ethnicity and sex. RESULTS: Low LR participants tended to decrease their usual (p < 0.06) and maximum (p < 0.05) drinks per occasion most prominently when assigned to the LR-based protocol, while those with High LRs improved more in the SOTA Group. The most robust differences were seen when controlling for ethnicity. The effect sizes were small to medium. CONCLUSIONS: These results support the advantages of carrying out prevention via the Internet and in tailoring the approach to a pre-existing phenotype.

The patterns of drug and alcohol use and associated problems over 30 years in 397 men.

BACKGROUND: Alcohol and drug use disorders (AUDs and SUDs) and their combination are relatively common and often occur together. However, the relationships of potential early life correlates of alcohol and drug disorders to the combined diagnoses have rarely been evaluated in long-term prospective studies or in populations at high risk of one of these diagnoses but not the other. METHODS: Data were analyzed from 397 males (half with an alcohol-dependent father) who had no AUDs or SUDs at age 20 and who were followed approximately every 5 years for 3 decades. Early life correlates and the course of AUDs, SUDs, and combined disorders were evaluated for 4 groups of subjects based on subsequent alcohol and/or drug diagnoses. RESULTS: While the overall rates of the development of AUDs and SUDs were 41 and 21%, respectively, the rates of the second substance-related diagnosis were almost 2-fold higher for individuals who had the first condition. Among potential risk factors, scores for externalizing traits were elevated for men with AUDs, SUDs, and their combination, but a low level of response (low LR) to alcohol was associated only with the risk of AUDs, even when observed in the context of SUDs. The same earlier life characteristics that related to AUDs and to SUDs also related to the combination of these diagnoses in the same person. Finally, in this prospective study, subjects with both AUDs and SUDs had a more severe course than subjects with either condition alone. CONCLUSIONS: This prospective evaluation of a group at high risk of AUDs confirmed the selective impact of the low LR on the risk of AUDs, the relationship of externalizing characteristics to both AUDs and SUDs and confirmed the more severe clinical course for both conditions when seen together.

Relationships among independent major depressions, alcohol use, and other substance use and related problems over 30 years in 397 families.

OBJECTIVE: Although heavy drinking is related to sadness on multiple levels, the link between alcohol use disorders (AUDs) and major depressive episodes (MDEs) is more controversial. One complicating factor is that some MDEs are temporary and only occur in the context of heavy drinking, whereas other MDEs are longer lasting and occur independently of intense alcohol intake (i.e., independent depressive episodes [IDEs]). We hypothesized that a longitudinal study that uses validated interviews with subjects and relatives and distinguishes between IDEs and alcohol-induced depressive episodes would reveal little evidence of a link between IDEs and AUDs. METHOD: Histories of AUDs, IDEs, and substance-induced depressions were prospectively evaluated over 30 years in 397 male probands from the San Diego Prospective Study and in their 449 offspring using questions extracted from the Semi-Structured Assessment for the Genetics of Alcoholism interview. RESULTS: The rate of IDEs over 30 years in the 397 probands was 15.3% overall. Among probands who developed AUDs, 31% of their depressive episodes were substance induced, not IDEs. For these men followed over 3 decades, those with IDEs had no increased rate of AUDs and evidenced no higher rate of use or abuse/dependence on illicit substances. Similar conclusions applied to their 449 offspring ages 12 years and older. CONCLUSIONS: These data support the importance of distinguishing between IDE and substance-induced depressions when evaluating the relationship between AUDs and depression syndromes.

Structuring a college alcohol prevention program on the low level of response to alcohol model: a pilot study.

BACKGROUND: New approaches are needed to bolster the modest effects of campus drinking prevention programs. However, more definitive research on new paradigms is very expensive, and in the current economic climate, progress can be made by evaluating smaller pilot studies. This study describes one such approach. METHODS: A sample of 18-year-old or older, healthy, drinking freshmen at our university was assigned to 2 groups stratified to be similar on demography, drinking histories, and their level of response (LR) to alcohol. In the spring quarter of the school year, the 32 subjects in each of 2 groups viewed four 45-minute Internet-based videotapes as part of 4 prevention sessions. All 8 modules were based on the same techniques and general content, but the 4 videos for the first group were structured around the validated model of how a low LR affects heavy drinking (the low level of response-based [LRB] Group), with partial mediation by heavier drinking peers, positive alcohol expectancies, and drinking to cope with stress. Videos for the state-of-the-art (SOTA) comparison group did not place the similar prevention messages into the low LR framework. Changes in drinking were evaluated at 3 times: before Module 1, before Module 4, and 1 month after Module 4. RESULTS: Usual and maximum drinks per occasion decreased over time for both high and low LR subjects in both LRB and SOTA groups. As predicted, the low LR students showed greater decreases in the LRB Group, while high LR students showed greater decreases in the more generic SOTA Group. CONCLUSIONS: The results support the hypothesis that tailoring prevention efforts to address specific predisposing factors, such as a low LR, may be associated with beneficial effects on drinking quantity. We hope that these data will encourage additional efforts to validate the low LR-based prevention paradigm and test other interventions that are targeted toward predisposing phenotypes such as impulsivity and negative affect.

Comparison across two generations of prospective models of how the low level of response to alcohol affects alcohol outcomes.

OBJECTIVE: This article presents the first direct comparison of level of response (LR)-based prospective models in two generations of the same families. To accomplish this, we describe results from the first prospective evaluation of potential mediators of how an earlier low LR to alcohol relates to adverse alcohol outcomes in offspring from the San Diego Prospective Study (SDPS). METHOD: To compare with data from probands in the SDPS, new data were gathered from 86 drinking offspring (age ~20 years) during the 25-year follow-up of these families. Consistent with the usual effect of a low LR, outcomes 5 years later for both generations focused on drinking quantities as well as alcohol problems during the follow-up. A structural equation model (SEM) was used to analyze the relationships among variables, and the models in proband and offspring generations were compared using direct observations of the model results and through invariance procedures. RESULTS: In these drinking offspring, LR correlated with 5-year outcomes (r = .48, p < .001) and the SEM R² was .48, with good fit statistics. As predicted, the LR relationship to alcohol-related outcomes was both direct and partially mediated by heavier peer drinking, positive alcohol expectancies, and using alcohol to cope with stress. These results were similar to a previously published prospective model in SDPS probands, although path coefficients were generally higher in the younger group. CONCLUSIONS: The LR-based model of heavier drinking operated similarly across generations, with some modest differences. These results indicate that the model may be meaningful in both younger and middle-age groups.

The investigation into CYP2E1 in relation to the level of response to alcohol through a combination of linkage and association analysis.

BACKGROUND: A low level of response to alcohol during an individual's early experience with alcohol is associated with an increase risk of alcoholism. A family-based genome-wide linkage analysis using sibling pairs that underwent an alcohol challenge where the level of response to alcohol was measured with the Subjective High Assessment Scale (SHAS) implicated the 10q terminal (10qter) region. CYP2E1, a gene known for its involvement with ethanol metabolism, maps to this region. METHODS: Variance component multipoint linkage analysis was performed on a combined map of single-nucleotide polymorphism (SNP) and microsatellite data. To account for the heterogeneity evident in the dataset, a calculation assuming locus heterogeneity was made using the Heterogeneity Log of Odds (HLOD) score. Association between SNP marker allele counts and copy number and SHAS scores were evaluated using a logistic regression model. RESULTS: Linkage analysis detected significant linkage to CYP2E1, which was diminished because of apparent locus heterogeneity traced to a single family with extreme phenotypes. In retrospect, circumstances recorded during testing for this family suggest that their phenotype data are likely to be unreliable. Significant allelic associations were detected for several CYP2E1 polymorphisms and the SHAS score. DNA sequencing from families that contributed the greatest evidence for linkage did not detect any changes directly affecting the primary amino acid sequence. With the removal of a single family, combined evidence from microsatellites and SNPs offers significant linkage between the level of response to alcohol and the region on the end of chromosome 10. CONCLUSION: Combined linkage and association indicate that sequence changes in or near CYP2E1 affect the level of response to alcohol providing a predictor of risk of alcoholism. The absence of coding sequence changes indicates that regulatory sequences are responsible. Implicating CYP2E1 in the level of response to alcohol allows inferences to be made about how the brain perceives alcohol.

Chromosome 15q25.1 genetic markers associated with level of response to alcohol in humans.

As with other genetically complex common psychiatric and medical conditions, multiple genetic and environmental components contribute to alcohol use disorders (AUDs), which can confound attempts to identify genetic components. Intermediate phenotypes are often more closely correlated with underlying biology and have often proven invaluable in genetic studies. Level of response (LR) to alcohol is an intermediate phenotype for AUDs, and individuals with a low LR are at increased risk. A high rate of concurrent alcohol and nicotine use and dependence suggests that these conditions may share biochemical and genetic mechanisms. Genetic association studies indicate that a genetic locus, which includes the CHRNA5-CHRNA3-CHRNB4 gene cluster, plays a role in nicotine consumption and dependence. Genetic association with alcohol dependence was also recently shown. We show here that two of the markers from the nicotine studies also show an association (multiple testing corrected P < 0.025) with several LR phenotypes in a sample of 367 siblings. Additional markers in the region were analyzed and shown to be located in a 250-kb expanse of high linkage disequilibrium containing three additional genes. These findings indicate that LR intermediate phenotypes have utility in genetic approaches to AUDs and will prove valuable in the identification of other genetic loci conferring susceptibility to AUDs.

Clinical implications of tolerance to alcohol in nondependent young drinkers.

BACKGROUND: Ten percent of teenagers and young adults with no alcohol diagnosis and a third of those with alcohol abuse report tolerance to alcohol. However, relatively few data are available on the clinical implications of tolerance in nondependent men and women. METHODS: Data were gathered from 649 18-to-22-year-old drinking offspring from the Collaborative Study on the Genetics of Alcoholism (COGA) families. The prevalence and clinical correlates of tolerance were evaluated across subjects with no DSM-IV alcohol abuse and no tolerance, similar individuals with tolerance, subjects with alcohol abuse but no tolerance, and individuals with both alcohol abuse and tolerance. RESULTS: Tolerance was associated with an almost doubling of the number of drinks needed to feel alcohol's effects, and correlated with additional alcohol-related problems. In regression analyses, the most consistent and robust correlates of tolerance were the maximum number of drinks and alcohol problems, and tolerance remained informative after covarying for drinking quantity. CONCLUSIONS: Tolerance to alcohol may be a useful concept regarding nondependent drinkers that is not just a proxy for alcohol quantity but also reflects the presence of additional problems.

A cross-generational comparison of alcohol challenges at about age 20 in 40 father-offspring pairs.

BACKGROUND: A low level of response (LR) to alcohol is one of several genetically-influenced phenotypes associated with an elevated risk for heavy drinking and alcoholism. While most studies support the influence of genes for this characteristic, no data to date have addressed how LR established from alcohol challenges performs in similarly aged subjects across generations. METHODS: Between 1978 and 1988, 18-to-25-year-old non-alcohol-dependent Caucasian male drinkers participated in the San Diego Prospective Study alcohol challenges. The paradigms included self-reports of feelings of "High" and "Intoxication," as well as alcohol-related changes in body sway. In recent years, 40 18-to-29-year-old offspring of 25 of these original probands were tested using a similar protocol. RESULTS: Despite the passage of two decades between laboratory sessions across generations, for family history positive (FHP) subjects, significant positive correlations were observed for subjective feelings of intoxication and body sway after alcohol. Parent-offspring correlations were in the predicted direction for subjective feelings for family history negatives (FHNs), but were not significant. Across offspring, LR values were lower for FHPs overall, with significant differences at 60 or 90 min for five items. CONCLUSIONS: The similarities in LR across generations, while not proving heritability, are consistent with prior reports regarding genetic influences in the LR to alcohol. The significant correlations across generations and over two decades support the reliability of the alcohol challenge results.

Autosomal linkage analysis for the level of response to alcohol.

BACKGROUND: The level of response (LR) to alcohol is a genetically-influenced phenotype related to the alcoholism risk. Usually measured by evaluating psychological and physiological changes that follow the administration of alcohol, the heritability of LR is estimated to be between 0.4 and 0.6, and efforts are being made to find genes related to this phenotype. This paper presents data from a family-based genome with linkage analysis focusing on alcohol challenge determinants of LR. METHODS: The subjects were 18-to-29-year-old sibling pairs with at least one parent who was alcohol-dependent and who had experience with alcohol but were not yet alcohol-dependent themselves. Both members of the sibling pairs were given oral alcohol challenges (0.75-0.90 ml/kg of ethanol for females and males, respectively), with LR established using the Subjective High Assessment Scale (SHAS) and changes in body sway (BS) repeatedly over a 3.5-hr. period. Blood samples from siblings and at least one parent were genotyped using 811 microsatellite markers, with results evaluated using several related variance component approaches as implemented in SOLAR for continuous traits. In addition, association was tested using single nucleotide polymorphisms (SNPs) within the KCNMA1, HTR7 and SLC18A2 genes that may relate to a finding on chromosome 10. RESULTS: Data were generated from 238 sib-pairs representing 365 individuals (41.6% were males) from 165 families. The most consistent results across methods and samples were observed for SHAS on chromosome 10 between 120 and 140 cM (with a maximum LOD score of 2.6 at 122 cM), and a second region of possible interest at 173 cM (LOD = 1.2). Statistical analysis with the KCNMA1, HTR7 and SLC18A2 genes, which lie in the support region of interest revealed no evidence for association after correction for multiple comparisons. CONCLUSIONS: These evaluations from the largest known alcohol challenge-based genetic study to date highlight the potential importance of genes on chromosome 10 as possible contributors to the low LR to alcohol as a risk factor for alcoholism.

The search for genes contributing to the low level of response to alcohol: patterns of findings across studies.

BACKGROUND: Alcoholism is a complex genetically influenced disorder in which multiple phenotypes [e.g., disinhibition, alcohol-metabolizing patterns, and the low level of response (LR) to alcohol] contribute to the risk. A low LR to alcohol is one of the more thoroughly studied risk phenotypes; data indicate that LR relates to the risk status, predicts future alcoholism, and has a heritability as high as 60%. This article reviews data from animal and human studies regarding the LR to alcohol, searching for a convergence of results that might lead to the identification of relevant genes. METHODS: A literature search was performed regarding animal and human genetic studies focusing on genes that might affect the LR to alcohol as a risk factor for alcoholism. The goal was to synthesize these results and highlight potential patterns. RESULTS: Focusing on both genetic linkage and association studies, a number of chromosomal regions and genes potentially relevant to findings across two or more sources were identified. The genes of potential interest fell into several categories, including second-messenger systems (e.g., G proteins, adenylyl cyclase, and protein kinases); neurotransmitters or drug-related receptors (e.g., gamma-aminobutyric acid-A, glutamate, serotonin, and cannabinoid and opioid receptors); genes that affect alcohol metabolism; and genes that might relate to an overlap in the risk for alcoholism and some psychiatric conditions (e.g., catechol-O-methyltransferase regarding schizophrenia and bipolar disorder). CONCLUSIONS: The review identifies several genes that may contribute to a low LR to alcohol and, thus, to an increased risk for alcohol use disorders. The chromosomal regions and genes highlighted here may form the basis for more focused genetic studies of alcohol use disorders, with the goals of developing more specific and effective prevention and treatment approaches.

Findings across subgroups regarding the level of response to alcohol as a risk factor for alcohol use disorders: a college population of women and Latinos.

BACKGROUND: The rates of alcohol dependence, a genetically influenced disorder, are increased among Latino men in the United States and are lower among women across ethnic groups. These analyses explored whether the differential rate of alcohol use disorders (AUDs) might reflect one genetically influenced phenotype related to alcoholism risk: the low level of response (LR) to alcohol. METHODS: A questionnaire was mailed to students at two universities to identify drinking but not alcohol-dependent 18- to 29-year-old men and women who had a parent with alcohol dependence. Subjects were subsequently screened with a validated semistructured interview to corroborate the personal and family histories, and they participated in a challenge with alcohol 0.75 ml/kg for women and 0.90 ml/kg for men. LRs to alcohol were determined and compared between genders and between Latino versus Caucasian/Anglo subjects. RESULTS: The data revealed no consistent significant differences between genders regarding either subjective feelings of intoxication or alcohol-induced changes in body sway. A similar lack of differential between groups was observed when Latino and Caucasian/Anglo subjects were compared. However, there was at least a statistical trend for interactions when gender, ethnicity, and time were considered together; there was some evidence for a higher LR in Latina women. Perhaps reflecting the different weights and doses of alcohol used, men demonstrated higher breath alcohol concentrations, but no differences in these values were noted between Latino and Anglo populations. CONCLUSIONS: The results indicate that the LR to alcohol is not likely to explain differences in rates of AUDs between genders or these two ethnic groups overall. The possibility that a higher LR might be seen for the subgroup with the lowest AUD rate--Latina women--will require replication in larger samples of well matched groups before definitive conclusions can be drawn.

The search for genes related to a low-level response to alcohol determined by alcohol challenges.

BACKGROUND: A low level of response (LR) to alcohol seems to relate to a substantial proportion of the risk for alcoholism and to have significant heritability. METHODS: This report describes the results of a genome-wide segregation analysis for the first 139 pairs of full siblings by using an alcohol challenge protocol as a direct measure of LR. Subjects from 18 to 29 years old were selected if the original screen indicated they had an alcohol-dependent parent, reported a personal history of drinking but had no evidence of alcohol dependence, and had a full sibling with similar characteristics. Body sway and Subjective High Assessment Scale scores were measured at baseline and at regular intervals after the administration of a measured dose of alcohol. Participants and available parents were genotyped for 811 microsatellite markers, and resulting data were analyzed with a variance component method. RESULTS: Nine chromosome regions with logarithm of the odds ratio (LOD) between 2.2 and 3.2 were identified; several had previously been implicated regarding phenotypes relevant to alcoholism and the LR to alcohol. Several regions identified in the previous linkage study by using a retrospective self-report questionnaire were potentially confirmed by this study. The strongest evidence was on chromosomes 10, 11, and 22. CONCLUSIONS: Several chromosomal areas seem to relate to the low LR to alcohol as a risk factor for alcohol dependence.