This investigation sought to determine the structure of the comorbidity among four adolescent phenotypes indexing externalizing behaviors: hyperactivity/impulsivity, inattention, conduct problems, and alcohol problems. Specifically, we sought to examine measured familial/environmental risk factors and their associations with externalizing behavior and alcohol problems and, once taking those measured risks into account, to determine what proportion of the variance and covariance among these phenotypes was due to biological risk, environmental risk, or both.
Major findings from these analyses include: (i) parental risk factors, such as parental alcohol dependence and regular smoking, increase risk for externalizing behavior; (ii) prenatal exposures predicted increased symptomatology for HYP/IMP (smoking during pregnancy), INATT and CDP (prenatal alcohol exposure); (iii) after adjusting for measured familial/prenatal risk factors, genetic influences were significant for HYP/IMP, INATT, and CDP; however, similar to earlier reports (Rhee et al., 2003
; Rose et al., 2004
), genetic effects on alcohol dependence symptoms were negligible, a finding consistent with the fact that, in adolescence, drinking tends to be exploratory and episodic with alcohol dependence symptoms being rarely endorsed (Rose et al., 2004
); and (iv) in adolescence, correlated liabilities for conduct and alcohol problems are found in environmental factors common to both phenotypes, while covariation among impulsivity, inattention, and conduct problems is primarily due to genetic influences common to these three behaviors.
Interestingly, while conduct problems were significantly associated with alcohol problems, there was no significant relationship between alcohol use symptomatology and both dimensions of ADHD (hyperactivity/impulsivity and inattention) in this adolescent female sample. This finding is not without precedent and is entirely consistent with earlier work by Moss and Lynch (2001)
who examined the relationships between conduct disorder, ADHD, and oppositional defiant disorder on subsequent alcohol use disorder. They found that, while male adolescents demonstrated direct effects of CD and ADHD on alcohol use disorder, female adolescent data only indicated a robust direct effect of CD on alcohol use disorder. Thus, findings stress the importance of considering gender effects, an issue that many studies in this area have been underpowered to detect (e.g., Molina et al., 2007
The present work should be interpreted in the context of its strengths and limitations. First, we are reliant on maternal report of ADHD symptoms and twins’ self-report for conduct and alcohol problems. Although maternal report has been shown to be reliable for ADHD (Faraone et al., 1995
) and other behavioral problems (e.g., Cronk et al., 2002
), the addition of multiple raters (i.e., direct clinical evaluation or teacher reports) of behavior may offer additional information. Second, while not a main outcome in the study, we are dependent on retrospectively-reported broadly-defined measures of substance use during pregnancy. This could have caused us to overestimate the importance of these risk factors. While considerable research supports reliability and validity of retrospective reporting of pregnancy variables (e.g. Christensen et al., 2004
; Heath et al., 2003
; Reich et al., 2003
), this does not preclude further investigation using more detailed assessments, including thorough timing and duration of exposure. Third, as with any cross-sectional study, the results are limited to a particular developmental period, in this case early to late adolescence. Further investigations are needed to determine whether the same relationships hold at both earlier (childhood) and later (adulthood) developmental periods. This is particularly important given recent work by Molina and colleagues (2007)
who demonstrated that childhood ADHD predicted heavy drinking, drunkenness, alcohol use disorder symptoms and alcohol use disorder for late adolescence but not for early adolescence. Further evidence for considering additional developmental stages, can be found in a genetic association study by Dick et al (2006)
who show that the GABRA2 gene is significantly associated with childhood CD symptoms but not with childhood alcohol dependence symptoms. However, they do show a consistent elevation in risk for alcohol dependence that is associated with GABRA2, but this association only becomes evident in the mid-20s and then remains throughout adulthood (Dick et al., 2006
Regarding its strengths, this study is the first genetically informative design to consider the specific relationships between dimensions of ADHD (i.e., hyperactive/impulsivity and inattention), conduct problems and alcohol use problems in adolescence. Also, families were recruited from the community rather than through a clinically referred proband, thus the results are likely to generalize to the population; although this also likely resulted in lower symptom endorsement and possibly less power to detect associations.
In summary, results of the present investigation indicate that, after controlling for prenatal and familial risk factors shown to increase risk for ADHD subtypes, conduct problems, and alcohol dependence symptomatology, most of the covariance among impulsivity, inattention, and conduct problems is due to common genetic influences; however, the observed comorbidity between conduct and alcohol problems is driven primarily by environmental influences common to both behaviors. Each phenotype is also under the influence of additional, unique genetic and/or environmental factors, suggesting that these externalizing disorders, while sharing some genetic and/or environmental influences, are not simply manifestations of the same underlying biological or environmental predisposition. Consistent with earlier reports, dimensions of ADHD were not significantly associated with alcohol problems in this adolescent female sample, and similar to earlier work (Knopik et al., 2005
; 2009), prenatal and familial predictors of behavior, while significant, did not mediate genetic risk on externalizing behavior. Thus, while a variety of adolescent problem behaviors are significantly correlated, the structure of that association may differ as a function of phenotype (e.g., comorbid HYP/IMP and CDP vs. comorbid CDP and AlcProb) and developmental course (childhood, adolescence and adulthood), a finding that could inform different approaches to research, treatment, and prevention. For example, when considering risk for alcohol problems in adolescence, early identification efforts might focus on conduct problems and environmental factors common to both. Additionally, focusing on shared genetic factors that influence a spectrum of externalizing behaviors, may aid in identifying susceptibility genes and understanding the biological pathways that affect vulnerability for a variety of poor outcomes (Dick et al., 2008
). To conclude, a greater understanding of the structure of comorbidity can have an important impact on public health and remediation efforts of the deleterious effects of behavioral disorders such that information on the underlying covariance structure can provide information on (i) putative risk factors (biological and/or environmental) for disorders, and (ii) clinical treatment, including medication (e.g., treatments efficacious for one disorder should be investigated as a potential treatment for the other disorder).