The effects of single nucleotide polymorphisms in glutamatergic neurotransmission genes on neural response to alcohol cues and craving

• Verfasst von: Bach, Patrick [VerfasserIn]
• Verfasst von: Mann, Karl [VerfasserIn]
• Verfasst von: Rietschel, Marcella [VerfasserIn]
• Verfasst von: Kiefer, Falk [VerfasserIn]
• Verfasst von: Vollstädt-Klein, Sabine [VerfasserIn]
• Titel: The effects of single nucleotide polymorphisms in glutamatergic neurotransmission genes on neural response to alcohol cues and craving
• Verf.angabe: Patrick Bach, Martina Kirsch, Sabine Hoffmann, Anne Jorde, Karl Mann, Josef Frank, Katrin Charlet, Anne Beck, Andreas Heinz, Henrik Walter, Marcella Rietschel, Falk Kiefer, Sabine Vollstädt-Klein
• E-Jahr: 2015
• Jahr: 19 August 2015
• Umfang: 11 S.
• Fussnoten: Gesehen am 14.12.2017
• Titel Quelle: Enthalten in: Addiction biology
• Ort Quelle: Hoboken, NJ [u.a.] : Wiley-Blackwell, 1996
• Jahr Quelle: 2015
• Band/Heft Quelle: 20(2015), 6, Seite 1022-1032
• ISSN Quelle: 1369-1600
• DOI: doi:10.1111/adb.12291
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Alcoholism
• Sach-SW: cue-reactivity
• Sach-SW: fMRI
• Sach-SW: glutamate receptors
• Sach-SW: relapse
• Sach-SW: single nucleotide polymorphisms
• K10plus-PPN: 1566380952

Abstract

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 (rmedOFC, medPFC = 0.403, P = 0.001, rlatOFC, 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.