Alcohol use and alcohol use disorder (AUD) exhibits strong age-related patterns, specifically, initiation and escalation in adolescence, peak use and prevalence in emerging adulthood, followed by a substantial decline in young adulthood. Underlying these general patterns, however, there is substantial variation in terms of the onset, persistence, and severity of AUD. These patterns are influenced by individual differences in brain structure and function both in terms of initial risk and the rate of neurological maturation, the latter of which is affected by alcohol and drug use. In addition to exposure to substances, however, a person's broader environmental context includes a number of influences that impact neural development and increase or decrease risk for AUD. Delineating the complex interplay among the different neural and environmental influences that contribute to the emergence and persistence versus desistence of AUD requires tracking the co-development between substance use, neural processes, and contextual variables prior to the initiation of use and continuing past young adulthood after which AUD rates have peaked and begun to decline. We propose to do so by continuing to follow two cohorts of offspring from the Michigan Longitudinal Study (MLS) who have been participating in longitudinal neuroimaging. The MLS is a high-risk family study with a high prevalence of substance use disorders in the parental generation (>60%). The offspring generation has been followed beginning at ages 3-5 years old with intensive assessments of individual-level and contextual risk factors at 3-year intervals and annual assessments of substance use and risk factors beginning at age 11. Longitudinal neuroimaging of MLS participants (N=340) at one- to two-year intervals began in either childhood (n=130; baseline Mage=10 years, current Mage=16 years) or young adulthood (n=210; baseline Mage=20 years, current Mage = 26 years) including structure, resting state, and task-related activation focused on cognitive control and reward processes. We propose additional longitudinal scans, up to age 21 in the child cohort, and up to age 30 in the young adult cohort. This will provide a dense number of assessments of brain structure, function and connectivity across the developmental period of childhood to young adulthood (ages 7-30). Our approach will emphasize sophisticated analytic methods to extract maximal information from the neuroimaging data (e.g., focus on circuit-based patterns using independent components analysis) to chart normative brain development, identify neurobiological risk for AUD, and determine the impact of alcohol use on brain development. We will also use longitudinal models to incorporate the role of environmental influences on both AUD and brain development with an emphasis on life transitions associated with increases (sexual initiation, leaving home) or decreases (marriage, parenthood) in alcohol use. The proposed study will be unique in the field with the potential to make key findings on the link between AUD and brain development.
Alcohol use disorder exhibits strong age-related variation?in terms of onset and persistence?which is influenced by neurobiological and contextual factors. We propose to extend a prospective neuroimaging study of risk for alcohol use disorder to cover ages 7 to 30, allowing us to identify neurobiological markers of risk and course (e.g., deterioration due to use) as well as the impact of contextual factors on brain development and patterns of alcohol use.
