Individual and additive effects of the CNR1 and FAAH genes on brain response to marijuana cues.
Individual and additive effects of the CNR1 and FAAH genes on brain response to marijuana cues.
复制标题
DOI：
10.1038/npp.2009.200
复制
发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
由于以前的工作强调了大麻素受体1(CNR1)和脂肪酸酰胺水解酶(FAAH)基因与大麻依赖(CD)有关的重要性，因此本研究试图描述这些遗传效应背后的神经机制。为此，我们收集了37名持续戒烟3天的普通大麻使用者的DNA样本和fMRI数据。根据受试者在先前与CD表型相关的两个单核苷酸多态(SNPs)上的基因型进行分组：CNR1中的rs2023239和FAAH中的rs324420。组间比较显示，CNR1rs2023239G等位基因携带者在暴露于大麻线索期间，在大脑中与奖励相关的区域，如眼眶额叶皮质(OFC)、额叶下回(IFG)和前扣带回(ACG)，比该SNP的A/A基因型携带者有更大的活动。FAAH组的对比显示，与FAAHA等位基因携带者相比，FAAHrs324420C纯合子在奖赏回路内的广泛区域也有更大的激活，特别是在OFC、ACG和伏隔核(NAC)。此外，OFC和NAC的神经反应与危险等位基因总数呈正相关(经聚类校正p<；0.05)。这些发现与以前报道的CNR1与FAAH和CD中间表型之间的关联是一致的，并表明这些遗传效应的潜在机制可能是CNR1 G等位基因和FAAH C/C基因型携带者对大麻线索的反应增强了大脑奖赏区域的神经反应。
Because previous work has highlighted the significance of the cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes with respect to cannabis dependence (CD), the present study sought to characterize the neural mechanisms that underlie these genetic effects. To this end, we collected DNA samples and fMRI data using a cue-elicited craving paradigm in 37 3-day-abstinent regular marijuana users. The participants were grouped according to their genotype on two single nucleotide polymorphisms (SNPs) previously associated with CD phenotypes: rs2023239 in CNR1 and rs324420 in FAAH. Between-group comparisons showed that carriers of the CNR1 rs2023239 G allele had significantly greater activity in reward-related areas of the brain, such as the orbitofrontal cortex (OFC), inferior frontal gyrus (IFG), and anterior cingulate gyrus (ACG), during exposure to marijuana cues, as compared to those with the A/A genotype for this SNP. The FAAH group contrasts showed that FAAH rs324420 C homozygotes also had greater activation in widespread areas within the reward circuit, specifically in the OFC, ACG, and nucleus accumbens (NAc), as compared to the FAAH A-allele carriers. Moreover, there was a positive correlation between neural response in OFC and NAc and the total number of risk alleles (cluster-corrected p<.05). These findings are in accord with previously reported associations between CNR1 and FAAH and CD intermediate phenotypes, and suggest that the underlying mechanism of these genetic effects may be enhanced neural response in reward areas of the brain in carriers of the CNR1 G allele and FAAH C/C genotype in response to marijuana cues.
登录
查看更多内容
影响因子：
1.7
作者：
French, ED;Dillon, K;Wu, XF
通讯作者：
Wu, XF
DOI：
10.1073/pnas.95.17.10269
发表时间：
1998-08-18
影响因子：
11.1
作者：
Diana, M;Melis, M;Gessa, GL
通讯作者：
Gessa, GL
影响因子：
5.7
作者：
Beckmann, CF;Jenkinson, M;Smith, SM
通讯作者：
Smith, SM
影响因子：
7.6
作者：
Franklin, Teresa R.;wang, Ze;Childress, Anna Rose
通讯作者：
Childress, Anna Rose
影响因子：
5.7
作者：
Deichmann, R;Gottfried, JA;Turner, R
通讯作者：
Turner, R