Document Detail


Genetic variation in the alpha synuclein gene (SNCA) is associated with BOLD response to alcohol cues.
MedLine Citation:
PMID:  23384371     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Preclinical studies implicate the gene encoding the alpha synuclein protein (SNCA) in the pathophysiology of alcohol dependence and dopamine neuron function. Results from clinical studies are less conclusive. Using neurobiological phenotypes in genetic studies, rather than typical heterogeneous diagnostic categories derived from self-report, may improve reliability across studies. This study aimed to examine whether polymorphisms in the SNCA gene were associated with alcohol taste cue-elicited responses in the brain, one such intermediate phenotype.
METHOD: A total of 326 heavy drinkers who underwent an alcohol taste task during functional magnetic resonance imaging (fMRI) also were genotyped. Analyses focused on two previously identified SNCA variants (rs2583985 and rs356168) as well as 27 other single nucleotide polymorphisms from the Illumina Human1M BeadChip that were used in an exploratory analysis of the whole gene. Neurobiological phenotypes were defined as fMRI blood oxygenation level-dependent (BOLD) responses to alcohol taste cue (vs. a control cue) in seven regions of interest known to be involved in cue processing and rich in dopaminergic axon terminals.
RESULTS: Polymorphisms in the SNCA gene were significantly correlated with BOLD activation. Specifically, the largest effect sizes and significance were seen for rs2583985 in paracingulate and caudate (focused analysis) and for rs1372522 in paracingulate (exploratory analysis). Activation in all regions of interest was correlated with alcohol-dependence severity.
CONCLUSIONS: SNCA genotype was found to be associated with the degree of fMRI BOLD response during exposure to the taste of alcohol versus a control taste. This study also further validates the use of this alcohol taste task as an intermediate phenotype for alcohol-dependence severity.
Authors:
Claire E Wilcox; Eric D Claus; Sara K Blaine; Marilee Morgan; Kent E Hutchison
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of studies on alcohol and drugs     Volume:  74     ISSN:  1938-4114     ISO Abbreviation:  J Stud Alcohol Drugs     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-06     Completed Date:  2013-07-22     Revised Date:  2014-03-06    
Medline Journal Info:
Nlm Unique ID:  101295847     Medline TA:  J Stud Alcohol Drugs     Country:  United States    
Other Details:
Languages:  eng     Pagination:  233-44     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Alcoholism / physiopathology*
Axons
Brain / physiopathology
Brain Mapping / methods
Cues
Dopamine / metabolism
Female
Functional Neuroimaging
Humans
Magnetic Resonance Imaging / methods*
Male
Oxygen / metabolism*
Polymorphism, Single Nucleotide
Severity of Illness Index
alpha-Synuclein / genetics*
Grant Support
ID/Acronym/Agency:
R01 AA012238/AA/NIAAA NIH HHS; R01 AA012238-07/AA/NIAAA NIH HHS; R01 AA014886/AA/NIAAA NIH HHS; R01 AA014886/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/alpha-Synuclein; S88TT14065/Oxygen; VTD58H1Z2X/Dopamine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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