Efforts to develop more effective treatment approaches for alcohol dependence will benefit from two lines of research: 1) a more precise characterization of the neurobiological mechanisms that underlie responses to alcohol cues and relapse;and 2) the identification of biomarkers (e.g., genetic variations) that reflect the functional significance of these mechanisms on an individual level, such that they might be used to match individuals with the treatment most likely to be effective for them. Consistent with these two overarching objectives, our focus over the last five years of support has been to integrate neuroimaging and genetic approaches to more precisely characterize the neurobiological mechanisms that putatively underlie reactivity to alcohol cues and to identify biomarkers associated with those mechanisms. The focus of data analyses to date has been the characterization of fMRI BOLD response to the presentation of alcohol cues (i.e., the taste of alcohol) and genetic variations that predict that response in a sample of 270 individuals with an alcohol use disorder. The results (see preliminary studies section) provide strong initial support for 100 single nucleotide polymorphisms (SNPs) that are associated with cue-elicited BOLD response in the striatum and prefrontal cortex. The overarching aim of this application for continuation of funding is to follow-up these analyses with an a priori hypothesis driven study designed to replicate individual SNP results. The research will also examine years of heavy alcohol abuse as an environmental variable that may interact with genetic variation to exacerbate changes in neuronal function in a sample of 320 individuals with alcohol use disorders.
This research combines neuroimaging and genetic approaches to examine how specific genetic variations are related to responses to alcohol cues. This research will also test whether the number of years of heavy alcohol exposure interacts with specific genetic variations to predict how people respond to alcohol cues. Improvements in our understanding of genetic factors and neurobiological mechanisms that influence the etiology of alcohol dependence is expected to have implications for new prevention and treatment approaches.
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|Monnig, Mollie A; Thayer, Rachel E; Caprihan, Arvind et al. (2014) White matter integrity is associated with alcohol cue reactivity in heavy drinkers. Brain Behav 4:158-70|
|Karoly, Hollis C; Weiland, Barbara J; Sabbineni, Amithrupa et al. (2014) Preliminary functional MRI results from a combined stop-signal alcohol-cue task. J Stud Alcohol Drugs 75:664-73|
|Harlaar, Nicole; Bryan, Angela D; Thayer, Rachel E et al. (2014) Methylation of a CpG site near the ALDH1A2 gene is associated with loss of control over drinking and related phenotypes. Alcohol Clin Exp Res 38:713-21|
|Bujarski, Spencer; Ray, Lara A (2014) Subjective response to alcohol and associated craving in heavy drinkers vs. alcohol dependents: an examination of Koob's allostatic model in humans. Drug Alcohol Depend 140:161-7|
|Karoly, Hollis C; Harlaar, Nicole; Hutchison, Kent E (2013) Substance use disorders: a theory-driven approach to the integration of genetics and neuroimaging. Ann N Y Acad Sci 1282:71-91|
|Liu, Jingyu; Calhoun, Vince D; Chen, Jiayu et al. (2013) Effect of homozygous deletions at 22q13.1 on alcohol dependence severity and cue-elicited BOLD response in the precuneus. Addict Biol 18:548-58|
|Karoly, Hollis C; Stevens, Courtney J; Thayer, Rachel E et al. (2013) Aerobic exercise moderates the effect of heavy alcohol consumption on white matter damage. Alcohol Clin Exp Res 37:1508-15|
|Wilcox, Claire E; Claus, Eric D; Blaine, Sara K et al. (2013) Genetic variation in the alpha synuclein gene (SNCA) is associated with BOLD response to alcohol cues. J Stud Alcohol Drugs 74:233-44|
|Claus, Eric D; Blaine, Sara K; Filbey, Francesca M et al. (2013) Association between nicotine dependence severity, BOLD response to smoking cues, and functional connectivity. Neuropsychopharmacology 38:2363-72|
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