Early subjective response and acquired tolerance as predictors of alcohol use and related problems in a clinical sample.

The period between adolescence and adulthood, referred to as “emerging adulthood” (age 18–25; Arnett, 2005), is a time of increased alcohol consumption and problematic drinking patterns (Johnston et al., 2010). In addition to acute negative consequences (Hingson et al., 2005), emerging adults are at elevated risk for developing Alcohol Use Disorders (AUDs) (Knight et al., 2002; Slutske, 2005). Studies from nationally representative U.S. samples show peak onset of AUDs between the ages of 18 and 29. Although this pattern is evident for both alcohol abuse and dependence, risk is most pronounced for dependence, with rates more than double that of any other age group (Grant et al., 2004). As emerging adults move into young adulthood (late 20s and early 30s) and undergo major role changes including full-time employment, marriage, and parenthood, there is a tendency to “mature out” of heavy drinking patterns (Jochman and Fromme, 2010). New onset cases of alcohol use disorders also decrease following emerging adulthood (Verges et al., 2012). Thus, identification of risk factors for heavy alcohol use and associated negative consequences during emerging adulthood is a major public health priority. Genetic influences on the development of alcohol-related problems are now well established. Risk for developing an AUD is roughly four times greater among individuals with a family history of alcoholism (NIAAA, 2007), and twin studies have found that nearly 50% of the variance in AUD risk is attributed to genetic factors (Knopik et al., 2004; Liu et al., 2004). Although genetic factors play an important role, the mechanisms through which they operate are only beginning to be uncovered. One potential mechanism of genetic influence is subjective response (SR) to alcohol, with differential sensitivity to the pharmacological effects of alcohol associated with risk for alcohol-related problems. Previous studies suggest that SR may account for as much as 40–60% of the variance in AUD risk associated with genetics (Schuckit, 1999). Most SR studies have used alcohol challenge paradigms to investigate individual differences in SR. Patterns of SR are then examined both as outcomes (e.g., differences in SR by family history status or heavy/light drinker status) and predictors of alcohol-related problems (See Morean and Corbin, 2010 and Quinn and Fromme, 2011 for recent reviews). Previous studies have identified both enhanced stimulation and reduced sedation/impairment in high-risk samples (Holdstock et al., 2000; King et al., 2002; 2011; Schuckit, 1980; 1984). Although a recent study also suggests that enhanced stimulant effects are associated with later risk for alcohol problems (King et al., 2011), evidence for the importance of SR as a predictor of later alcohol problems has been most consistently demonstrated for a low SR to sedation/impairment (Schuckit, 1994; Schuckit and Smith, 2000; Schuckit et al., 2004; Trim et al., 2009). Conceptually, a low response to negatively experienced alcohol effects contributes to risk through a faulty feedback system in which individuals do not receive the signal to stop drinking despite high blood alcohol concentrations (BACs). Thus, individuals with a low SR may consume larger quantities of alcohol, leading to tolerance, which in turn confers risk for AUDs (Schuckit, 1994). Although it is presumed that a low SR reflects an innate difference in response to alcohol, alcohol challenge paradigms are not well suited to identifying innate (e.g., early) alcohol responses since participants must be 21 or over. Responses reported at age 21 may reflect either a low innate response to alcohol or differential development of tolerance. It is important to differentiate early SR from tolerance given that tolerance is an alcohol dependence diagnostic criterion (APA, 2000). Unfortunately, there is limited human research on individual differences in the development of tolerance. The most comprehensive study of chronic tolerance to date used a sample of non alcohol dependent young adult offspring from the Collaborative Study on the Genetics of Alcoholism (COGA), and found that greater tolerance was associated with heavier drinking and more alcohol-related problems (Schuckit et al., 2008). Moreover, the effects of tolerance remained when controlling for drinking behavior. There is also some evidence of important individual differences in tolerance from lab-based studies. For example, a series of studies by Newlin and Thomson (1991, 1999) demonstrated that individuals with a family history of alcoholism differed from those without a family history on both sensitization and tolerance to alcohol effects. In summary, research on the importance of individual differences in tolerance to alcohol as a predictor of alcohol-related problems warrants further attention. Although alcohol challenge studies are generally unable to distinguish between the effects of early SR and tolerance, the Self-Rating of the Effects of Alcohol (SRE) measure (Schuckit et al., 1997) has the potential to disentangle these effects. The SRE asks individuals to report the number of drinks they need to consume to produce four separate effects (any effect, dizziness or slurred speech, stumbling gait, and passing out) during three different periods in their drinking history (first 5 drinking occasions, period of heaviest drinking, and most recent 3 months of regular drinking). Tolerance is conceptualized as an increase in the number of drinks needed to feel alcohol effects from early (first five) to later (most recent 3 months) drinking experiences. Although the SRE has its own limitations (i.e. self-reports of drinking experiences that occurred many years prior), Schuckit et al. (2010) found that the SRE and an alcohol-challenge-based measure of SR performed similarly in structural equation models evaluating the relationship between SR and future heavy drinking. Further, using the SRE to assess acquired tolerance has potential advantages over single item measures. The SRE-based measure assesses multiple alcohol effects, and by evaluating drinking at two separate time points, tolerance scores calculated as the difference between the two time points may be less biased than simple self-reports of subjective changes in the experience of alcohol effects for a given number of drinks over time. Further, by providing a continuous tolerance score, the SRE based measure is not subject to individual differences in how individuals define the presence or absence of acquired tolerance (Schuckit et al., 2008). Supporting the potential of this approach, a recent study using the SRE to assess early SR and tolerance found that both were independent predictors of use and problems in a sample of undergraduate students (Morean and Corbin, 2008). In the current study, we sought to replicate the Morean and Corbin (2008) study in a sample of heavy drinking young adults. Although research using the SRE has contributed to our understanding of early SR and tolerance, most studies have focused on light to moderate drinkers, and the few studies looking at heavier drinkers have used samples in their mid thirties and older. By that time, individuals are likely on an established trajectory of higher or lower-risk alcohol use. Further, the one study that differentiated early SR from acquired tolerance used a light to moderate drinking sample that reported relatively few alcohol-related problems. Thus, it is unclear to what extent an early SR and tolerance contribute to patterns of drinking behavior associated with more clinically significant problems. In the current study, we examined early SR and acquired tolerance as simultaneous predictors of both alcohol use and alcohol-related problems. With respect to alcohol use, we anticipated that the results would be similar to prior studies with a low early SR and greater acquired tolerance associated with heavier drinking. Our hypotheses regarding alcohol-related problems were more exploratory, as participants in the current sample were much heavier drinkers than in the Morean and Corbin (2008) study. Although this prior study found that a low early SR was associated with more alcohol-related problems, experienced heavy drinkers may learn to more effectively avoid acute drinking consequences, and this may be more pronounced among individuals with a low innate response to alcohol and/or greater acquired tolerance.