The effects of single nucleotide polymorphisms in glutamatergic neurotransmission genes on neural response to alcohol cues and craving
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-reactiv...
Gespeichert in:
| Hauptverfasser: | , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
19 August 2015
|
| In: |
Addiction biology
Year: 2015, Jahrgang: 20, Heft: 6, Pages: 1022-1032 |
| ISSN: | 1369-1600 |
| DOI: | 10.1111/adb.12291 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1111/adb.12291 Verlag, Volltext: http://onlinelibrary.wiley.com.ezproxy.medma.uni-heidelberg.de/doi/10.1111/adb.12291/abstract 
|
| Verfasserangaben: | 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 |
| Zusammenfassung: | 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. |
|---|---|
| Beschreibung: | Gesehen am 14.12.2017 |
| Beschreibung: | Online Resource |
| ISSN: | 1369-1600 |
| DOI: | 10.1111/adb.12291 |