One goal of the proposed study is to evaluate the connections of three genes implicated in risk for externalizing disorders to: (1) impairments in specific domains of brain function that have also been implicated in risk for these disorders; and (2) an impairment in the maturation of these domains. Another goal is to evaluate the shared connections of the genes and brain dysfunction to both body mass/adiposity and alcoholism risk.
The specific aims are: 1) To evaluate 150 girls, aged 14-16 yrs, and 150 girls, aged 16-18 yrs. The analysis will test for differences between the age cohorts in neurophysiological and behavioral signs of frontal and paralimbic brain function. The sample size of 300 establishes a foundation upon which we may, in a future application, build a longitudinal study and test for maturational change directly. 2) To test the association of neurophysiological and behavioral signs of frontal/paralimbic brain function, as well as their maturational change, with CHRM2, GABRA2, and ANKK1 gene polymorphisms. It is hypothesized that the genes will associate with different domains of dysfunction: (a) CHRM2 will primarily associate with impairments, and less change with age, in selective attention, working memory, and boredom susceptibility, (b) GABRA2 will primarily associate with motor impulsivity and response disinhibition, and less change in these domains with age. (c) The TaqlA and nearby polymorphisms in ANKK1 will primarily associate with reward seeking and response disinhibition, and less change in these domains with age. 3) To test the associations of the candidate genes, and neurophysiological and behavioral measures, with adiposity. An additional aim is to assess their association with various indicators of alcoholism risk, such as a smaller subjective response to alcohol and earlier ages at first use and first intoxication. It is hypothesized that all of the genetic and impulsivity measures will correlate with body mass/adiposity and alcoholism risk outcomes because all are indicators of an externalizing construct that promotes them.
The proposed study focuses on a health outcome of growing public health significance-an overweight or obese body mass~and risk factors for alcoholism. A better understanding of the overlap of these disorders could be significant. It may suggest, for example, that alcoholism and obesity are both expressions of an underlying externalizing trait which therefore require similar prevention and treatment strategies.
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