The effects of single nucleotide polymorphisms in glutamatergic neurotransmission genes on neural response to alcohol cues and craving
The effects of single nucleotide polymorphisms in glutamatergic neurotransmission genes on neural response to alcohol cues and craving
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DOI：
10.1111/adb.12291
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发表时间：
2015-11-01
影响因子：
3.4
通讯作者：
Vollstaedt-Klein, Sabine
中科院分区：
文献类型：
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作者：
Bach, Patrick;Kirsch, Martina;Vollstaedt-Klein, Sabine
本研究的目的是确定N-甲基-d-天冬氨酸受体（GRIN 1，GRIN 2A，GRIN 2C）和红藻氨酸受体（GRIK 1）基因中的四个单核苷酸多态性（SNP）对行为，神经线索反应性和饮酒结果的基因型效应。86戒酒酒精依赖患者从住院设置招募。神经心理学测试，基因分型和功能磁共振成像（fMRI）被用来研究基因型的影响。GRIN 2C风险等位基因携带者显示酒精线索诱导的前扣带皮层（ACC）和背外侧前额叶皮层（dlPFC）激活增加。前扣带回的神经元激活与酒精渴求呈正相关（r=0.201，P=0.032），而背外侧前额叶皮层的神经元激活与酒精渴求呈负相关（r=-0.215，P =0.023）。此外，dlPFC激活预测首次复发时间（HR=2.701，95%CI 1.244-5.864，P=0.012）。GRIK 1风险等位基因携带者在内侧前额叶（PFC）和眶额皮质（OFC）以及外侧PFC和OFC中表现出增加的线索诱导激活。两个簇中的激活与酒精渴求呈正相关（r（medOFC，medPFC）=0.403，P=0.001，r（latOFC，latPFC）=0.282，P=0.008），包含中间OFC的簇中的激活预测首次复发时间（HR=1.911，95%CI 1.030-3.545，P=0.040）。研究结果表明，GRIN 2C和GRIK 1基因中的SNPs与改变的线索诱导的大脑激活有关，这与对酒精的渴望和复发风险有关。
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.