CHARACTERIZING DYNAMIC RISK IN THE PATHWAY TO ALCOHOL DEPENDENCE: REPLY TO COMMENTARIES
Addiction (207)102 (2), 189–190.
CAROLYN E. SARTOR, MICHAEL T. LYNSKEY, ANDREW C. HEATH
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CHARACTERIZING DYNAMIC RISK IN THE PATHWAY TO ALCOHOL DEPENDENCE: REPLY TO COMMENTARIES
We would like to thank Drs McGue [1], Sher [2] and Zucker [3] for their insightful commentaries on our paper and agree that there are still many unknowns in our understanding of transitions in alcohol use and the unfolding of risk across the life span. Risk factors that shape the pathway to alcohol dependence are dynamic in nature, fluctuating in potency throughout the multi-stage process during which the disorder develops [4]. As a result, identification of risk factors associated with a life time dependence diagnosis, although important in assessing overall liability to the disorder, is of limited utility in predicting changes in vulnerability to alcohol-related problems over time—an essential step toward distinguishing those junctures where alcohol outcomes may be most modifiable. As evidenced in the findings and noted in Dr Sher's commentary [2], variability in risk over the course of alcohol dependence development is a function of phase of the disorder in combination with stage of development, such that rate of progression and prominence of risk factors associated with transitions would be expected to differ, for example, between an individual initiating alcohol use at 12 versus 18 years of age. Investigation of the underlying mechanisms driving stage transitions in alcohol dependence course requires an approach that takes into account shifts in environmental sources of influence that occur as a consequence of increased severity of drinking behaviors, as well as those attributable to age-related maturation. Twin and other genetically-informative research, which has produced evidence of distinctions in risk profiles between initiation of alcohol use (14–40% heritable, with the majority of variance accounted for by shared environment) [5–7] and alcohol dependence (50–60% heritable) [8–10] is a critical tool for conducting such investigations.
The complex interplay of genetic and environmental risk factors that change over time as a function of both alcohol exposure and developmental stage presents the challenging task of disentangling sources of variance accounting for considerable heterogeneity in trajectories of alcohol dependence. Prospective assessment of psychiatric and psychosocial risk factors conducted in the context of a gene by environment (G × E) research design would create a framework for determining the role of specific environmental correlates of alcohol-related problems and their interactions with genetic liability to alcohol dependence in the manifestation of alcohol outcomes (and indicators of developmental course) at varying stages of the disorder. Beyond addressing continuity in risk for alcohol outcomes posed by a given risk factor, continuity in the degree to which genetic predisposition to alcohol dependence interacts with that factor to increase alcohol-related risk at various stages of the disorder can be assessed. For example, high genetic liability to alcohol dependence in combination with externalizing psychopathology may be associated with early age at alcohol use initiation, but rate of progression to first dependence symptom may not differ by genetic liability for individuals with externalizing disorders. In addition to characterizing fluctuations in G × E effects on alcohol outcomes, such a genetically-informative design would provide the opportunity to extend the small but growing literature on shared genetic influences on cross-stage alcohol outcomes [11] and heritability of transitions in the course of alcohol use [12] that informs etiological models of alcohol dependence development.
CAROLYN E. SARTOR , MICHAEL T. LYNSKEY & ANDREW C. HEATH
