This prospective high-risk family study, the Michigan Longitudinal Study (MLS) began 27 years ago to characterize the development of risk for alcohol use disorder (AUD) among children (2nd generation or G2s) beginning prior to school entry, with the aims to detect whether risk markers of later disorder could be identified very early, to characterize the evolution of identified risk factors over the course of childhood and early adulthood, and to identify mediators and moderators of risk development that could guide prevention or early intervention programming.
Aims for the parents (G1s) were to identify factors that predict relapse, remission, and social adaptation. The project is the earliest beginning (age 3) high risk for AUD study currently active, and involves one of the longest spans of prospective assessment of alcohol/other drug use. Its data matrix involves repeated measurement of a variable network of behavioral, cognitive, and psychological functioning, social environment, substance use/abuse, and psychiatric symptoms. It is also interdigitated with 5 other projects which utilize the MLS as their recruitment, data management, and conceptual core, and share all data. This renewal application proposes continued characterization of G2s as the scientifically most unique segment of the study, limiting G1 assessments to measures critical to characterizing the socialization environment of G2s. G2s have been assessed since preschool and drinking/other drug use is assessed from time of onset. Continued collection of these data will allow evaluation of the prospective effects of precursive risk, in interaction with early substance use, upon later behavior. We intend to fully characterize two critical issues in G2s: 1) Identification of the developmental risk pathways that lead to an AUD outcome without psychiatric comorbidity as contrasted with one involving a comorbid externalizing or internalizing diagnosis;
(Aim 1); and 2) Identification of the factors that predict a resilient (non-alcohol abusing) outcome in emerging adulthood, despite precursive exposure to adversity (Aim 2). Furthermore, we intend to take advantage of the comprehensive multi-domain matrix of data available from the core study and its offshoot partner-projects to build cross-level, developmental models of mechanistic structure for critical risk and resilience phenotypes for problem alcohol use and AUD across levels of genes, neural networks, social environment, and development (Aim 3). In order to fully capitalize on the maturity of the study, we will also use th extensive multi-wave database to characterize a critical issue in the G1s: evaluating the long term effects of alcohol consumption burden upon cognitive function in middle to later adulthood (Aim 4). With more than a generation of real time information the project will be able to prospectively evaluate these effects over the course of 27 years. Finally, we intend to provide the now very long-term longitudinal database as a resource for the field. Thus, our final aim is to establish a project development program involving meetings adjunctive to RSA and CPDD for investigators to share data and issues, with the goal of developing a collaborative network (Aim 5).

Public Health Relevance

This project will provide in depth understanding of four issues of major importance to the field and the general public: It will identify individual and environmental factors in earlier life that predict a long-term resilient outcome in early adulthood despite exposure to significant adversity;it will identify factors that differentiate the form of alcoholism that is most likely to remit, namely alcoholism without psychiatric comorbidity, from those more recalcitrant forms of the disorder involving alcoholism and concurrent other psychiatric disorder;it will evaluate the extent to which social factors may arrest or protect against the long term effects of alcohol on cognitive impairment in middle age and older life;and it will make use of a unique, long-term multi-project collaboration to understand the interactions of genes, brain function, behavior, and social influence upon the development of impulsivity and of resilience over the course of childhood. Findings have the potential to open new avenues for prevention and treatment based upon an understanding of how these systems interact.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA007065-27
Application #
8707907
Study Section
Risk, Prevention and Intervention for Addictions Study Section (RPIA)
Program Officer
Bechtholt, Anita
Project Start
1987-04-01
Project End
2018-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
27
Fiscal Year
2014
Total Cost
$668,011
Indirect Cost
$238,422
Name
University of Michigan Ann Arbor
Department
Psychiatry
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Heitzeg, Mary M; Villafuerte, Sandra; Weiland, Barbara J et al. (2014) Effect of GABRA2 genotype on development of incentive-motivation circuitry in a sample enriched for alcoholism risk. Neuropsychopharmacology 39:3077-86
Heitzeg, Mary M; Nigg, Joel T; Hardee, Jillian E et al. (2014) Left middle frontal gyrus response to inhibitory errors in children prospectively predicts early problem substance use. Drug Alcohol Depend 141:51-7
Zucker, Robert A (2014) Genes, brain, behavior, and context: the developmental matrix of addictive behavior. Nebr Symp Motiv 61:51-69
Carter, R Colin; Jacobson, Joseph L; Dodge, Neil C et al. (2014) Effects of prenatal alcohol exposure on testosterone and pubertal development. Alcohol Clin Exp Res 38:1671-9
Weiland, Barbara J; Heitzeg, Mary M; Zald, David et al. (2014) Relationship between impulsivity, prefrontal anticipatory activation, and striatal dopamine release during rewarded task performance. Psychiatry Res 223:244-52
Hardee, Jillian E; Weiland, Barbara J; Nichols, Thomas E et al. (2014) Development of impulse control circuitry in children of alcoholics. Biol Psychiatry 76:708-16
Glaser, Yi G; Zubieta, Jon-Kar; Hsu, David T et al. (2014) Indirect effect of corticotropin-releasing hormone receptor 1 gene variation on negative emotionality and alcohol use via right ventrolateral prefrontal cortex. J Neurosci 34:4099-107
Weiland, Barbara J; Korycinski, Steven T; Soules, Mary et al. (2014) Substance abuse risk in emerging adults associated with smaller frontal gray matter volumes and higher externalizing behaviors. Drug Alcohol Depend 137:68-75
Villafuerte, S; Heitzeg, M M; Foley, S et al. (2012) Impulsiveness and insula activation during reward anticipation are associated with genetic variants in GABRA2 in a family sample enriched for alcoholism. Mol Psychiatry 17:511-9
Glass, Jennifer M; Buu, Anne; Adams, Kenneth M et al. (2009) Effects of alcoholism severity and smoking on executive neurocognitive function. Addiction 104:38-48

Showing the most recent 10 out of 38 publications