FMRI and Cognition of Youth at Risk for Alcoholism

$323,110R01FY2004AANIH

Veterans Medical Research Fdn/San Diego, San Diego CA

Investigators

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Abstract

DESCRIPTION (provided by applicant): The goal of this project is to better understanding brain characteristics that are premorbid to alcohol dependence by examining children at risk for alcohol problems using functional magnetic resonance imaging (fMRI) and neuropsychological (NP) testing. Our previous fMRI and NP studies suggested that protracted alcohol use during youth is associated with neurocognitive decrements in functioning. However, the extent to which these problems are caused by alcohol use cannot be ascertained until pre-existing status is well characterized. Several factors have reliably predicted the development of alcohol use disorders in youth, especially having a dense family history of alcohol dependence (FH) and meeting diagnosis for conduct disorder (CD) early in adolescence. This project will compare fMRI and NP performances in 4 groups of children with different levels of risk for developing alcohol dependence, FH+/CD+, FH+CD-, FH-/CD+, and FH-/CD-, in a 2x2 design. Each group will consist of 30 carefully screened 12-14 year olds recruited from two representative middle schools and the local juvenile justice system. NP tests will cover working memory attention, learning and retention, visuospatial, language, and executive functioning. FMRI will evaluate homodynamic changes during the performance of two challenging working memory tasks that required similar skills as NP tests that were impaired among alcohol dependent youth. These tasks produce signal contrast in brain regions that were related to FH and CD in electrophysiological and other studies. Our specific aims are to: 1) contrast neurocognition and brain functioning in FH+ (high-risk) youth to FH- (low-risk) control youth, 2) compare NP and fMRI results in CD+ (high-risk) youth to CD- (low-risk) youth, and 3) contrast the degree of abnormal neurocognition and brain functioning in each risk factor group using an interaction model. These results will be contrasted to existing fMRI and NP data on alcohol dependent teens from our current study. Further, this cohort may form the basis for a subsequent longitudinal investigation. This proposal will characterize abnormalities related to risk for alcohol dependence and help determine the extent to which neurocognitive deficits associated with alcohol dependence are due to premorbid factors.

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