Journal
ADDICTION BIOLOGY
Volume 20, Issue 6, Pages 1022-1032Publisher
WILEY
DOI: 10.1111/adb.12291
Keywords
Alcoholism; cue-reactivity; fMRI; glutamate receptors; relapse; single nucleotide polymorphisms
Categories
Funding
- 'Deutsche Forschungsgemeinschaft' [SFB 636]
- 'Bundesministerium fur Bildung und Forschung' [FKZ 01GS0117/NGFN, FKZ 01GS08152/NGFN Plus, FKZ 01ZX1311A/e, FKZ 01ZX1311E/e]
- 'Ministerium fur Wissenschaft, Forschung und Kunst'(MWK) in Baden-Wuerttemberg
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The aim of the current study was to determine genotype effects of four single nucleotide polymorphisms (SNPs) in the genes of the N-Methyl-d-aspartate receptor (GRIN1, GRIN2A, GRIN2C) and kainate receptor (GRIK1), which have been previously associated with alcoholism, on behavior, neural cue-reactivity and drinking outcome. Eighty-six abstinent alcohol dependent patients were recruited from an in-patient setting. Neuropsychological tests, genotyping and functional magnetic resonance imaging (fMRI) were used to study genotype effects. GRIN2C risk allele carriers displayed increased alcohol cue-induced activation in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (dlPFC). Neural activation in the ACC positively correlated with craving for alcohol (r=0.201, P=0.032), whereas activation in the dlPFC showed a negative association (r=-0.215, P=0.023). In addition, dlPFC activation predicted time to first relapse (HR=2.701, 95%CI 1.244-5.864, P=0.012). GRIK1 risk allele carriers showed increased cue-induced activation in the medial prefrontal (PFC) and orbitofrontal cortex (OFC) and in the lateral PFC and OFC. Activation in both clusters positively correlated with alcohol craving (r(medOFC, medPFC)=0.403, P=0.001, r(latOFC, latPFC)=0.282, P=0.008), and activation in the cluster that encompassed the medial OFC predicted time to first relapse (HR=1.911, 95%CI 1.030-3.545, P=0.040). Findings indicate that SNPs in the GRIN2C and GRIK1 genes are associated with altered cue-induced brain activation that is related to craving for alcohol and relapse risk.
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