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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA012238-15
Application #
8504886
Study Section
Special Emphasis Panel (ZRG1-BDCN-N (02))
Program Officer
Matochik, John A
Project Start
1998-09-21
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
15
Fiscal Year
2013
Total Cost
$566,080
Indirect Cost
$178,346
Name
The Mind Research Network
Department
Type
DUNS #
098640696
City
Albuquerque
State
NM
Country
United States
Zip Code
87106
Chen, Jiayu; Hutchison, Kent E; Bryan, Angela D et al. (2018) Opposite Epigenetic Associations With Alcohol Use and Exercise Intervention. Front Psychiatry 9:594
Vergara, Victor M; Weiland, Barbara J; Hutchison, Kent E et al. (2018) The Impact of Combinations of Alcohol, Nicotine, and Cannabis on Dynamic Brain Connectivity. Neuropsychopharmacology 43:877-890
Bidwell, L Cinnamon; Karoly, Hollis C; Thayer, Rachel E et al. (2018) DRD2 promoter methylation and measures of alcohol reward: functional activation of reward circuits and clinical severity. Addict Biol :
Karoly, Hollis C; Thayer, Rachel E; Hagerty, Sarah L et al. (2017) TLR4 Methylation Moderates the Relationship Between Alcohol Use Severity and Gray Matter Loss. J Stud Alcohol Drugs 78:696-705
Thayer, Rachel E; YorkWilliams, Sophie; Karoly, Hollis C et al. (2017) Structural neuroimaging correlates of alcohol and cannabis use in adolescents and adults. Addiction 112:2144-2154
Gardiner, Casey K; YorkWilliams, Sophie L; Bryan, Angela D et al. (2017) Body mass is positively associated with neural response to sweet taste, but not alcohol, among drinkers. Behav Brain Res 331:131-134
Hagerty, Sarah L; Bidwell, L Cinnamon; Harlaar, Nicole et al. (2016) An Exploratory Association Study of Alcohol Use Disorder and DNA Methylation. Alcohol Clin Exp Res 40:1633-40
Thayer, Rachel E; Hagerty, Sarah L; Sabbineni, Amithrupa et al. (2016) Negative and interactive effects of sex, aging, and alcohol abuse on gray matter morphometry. Hum Brain Mapp 37:2276-92
Weiland, Barbara J; Sabbineni, Amithrupa; Calhoun, Vince D et al. (2015) Reduced executive and default network functional connectivity in cigarette smokers. Hum Brain Mapp 36:872-82
Weiland, Barbara J; Thayer, Rachel E; Depue, Brendan E et al. (2015) Daily marijuana use is not associated with brain morphometric measures in adolescents or adults. J Neurosci 35:1505-12

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