期刊
FRONTIERS IN PSYCHOLOGY
卷 7, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fpsyg.2016.00464
关键词
circadian; alcohol; stress; PER1; ventral striatum; GxE; early life stress
资金
- Duke University
- National Institutes of Health [NIDA DA033369, NIDA DA031579, NIA R01-AG045231]
- NIMH [T32-MH014677, T32-GM008151]
- HHMI
- NSF [DGE-1143954]
- Klingenstein Third Generation Foundation
- National Heart, Lung, and Blood Institute [K08HL112961]
- National Science Foundation [DGE-1143954]
- Mr. and Mrs. Spencer T. Olin Fellowship for Women in Graduate Study
Increasing evidence suggests that the circadian and stress regulatory systems contribute to alcohol use disorder (AUD) risk, which may partially arise through effects on reward-related neural function. The C allele of the PER1 rs3027172 single nucleotide polymorphism (SNP) reduces PER1 expression in cells incubated with cortisol and has been associated with increased risk for adult AUD and problematic drinking among adolescents exposed to high levels of familial psychosocial adversity. Using data from undergraduate students who completed the ongoing Duke Neurogenetics Study (DNS) (n = 665), we tested whether exposure to early life stress (ELS; Childhood Trauma Questionnaire) moderates the association between rs3027172 genotype and later problematic alcohol use (Alcohol Use Disorders Identification Test) as well as ventral striatum (VS) reactivity to reward (card-guessing task while functional magnetic resonance imaging data were acquired). Initial analyses found that PERI rs3027172 genotype interacted with ELS to predict both problematic drinking and VS reactivity: minor C allele carriers, who were also exposed to elevated ELS reported greater problematic drinking and exhibited greater ventral striatum reactivity to reward-related stimuli. When gene x covariate and environment x covariate interactions were controlled for, the interaction predicting problematic alcohol use remained significant (p < 0.05, corrected) while the interaction predicting VS reactivity was no longer significant. These results extend our understanding of relationships between PER1 genotype, ELS, and problematic alcohol use, and serve as a cautionary tale on the importance of controlling for potential confounders in studies of moderation including gene x environment interactions.
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