GRIK1 Genotype and Daily Expectations of Alcohol's Positive Effects Moderate the Reduction of Heavy Drinking by Topiramate
GRIK1 Genotype and Daily Expectations of Alcohol's Positive Effects Moderate the Reduction of Heavy Drinking by Topiramate
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DOI：
10.1037/a0038350
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发表时间：
2014-12-01
影响因子：
2.3
通讯作者：
Covault, Jonathan
中科院分区：
文献类型：
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作者：
Kranzler, Henry R.;Armeli, Stephen;Covault, Jonathan
使用在138名重度饮酒者的治疗访问期间获得的回顾性报告，我们发现托吡酯对重度饮酒的减少由GRIK 1中的多态性（rs 2832407）调节，GRIK 1编码GluK 1红藻氨酸亚基（Kranzler等人，2014年a）。随后对12周托吡酯治疗试验的分析显示，药物和基因型对通过交互式语音应答技术获得的每日饮酒报告的影响相似（IVR; Kranzler等人，2014年b）。具体来说，rs 2832407 * C等位基因纯合子治疗托吡酯报告的饮酒水平低于那些接受安慰剂。这一组在饮酒的预期积极影响方面也有最大的下降（即，欲饮，欲饮。为了扩展该分析，该分析侧重于欲望和期望的平均水平如何随着治疗时间的推移而变化，我们使用了一种人内方法来检查期望和饮酒欲望的每日变化是否与托吡酯治疗和基因型相互作用，以预测夜间饮酒水平。与先前的分析（Kranzler等人，2014 b），在这里，我们关注的是酒精预期和饮酒欲望是否会减轻托吡酯对饮酒的影响。结果显示，基因型和药物的每日预期的3向相互作用，如托吡酯对rs 2832407 * C等位基因纯合子夜间饮酒的保护作用下降的日子，其特征是相对较高水平的预期酒精的积极作用。饮酒欲望或消极的酒精预期没有调节作用。因此，基因型和认知过程对托吡酯的作用有特定的调节作用。
Using retrospective reports obtained during treatment visits in 138 heavy drinkers, we found that topiramate's reduction of heavy drinking was moderated by a polymorphism (rs2832407) in GRIK1, which encodes the GluK1 kainate subunit (Kranzler et al., 2014a). A subsequent analysis of that 12-week topiramate treatment trial showed similar effects of medication and genotype on daily drinking reports obtained via interactive voice response technology (IVR; Kranzler et al., 2014b). Specifically, rs2832407*C-allele homozygotes treated with topiramate reported lower levels of drinking than those receiving placebo. This group also had the largest decreases in the expected positive effects of drinking (i.e., expectancies) and desire to drink. To extend that analysis, which focused on how mean levels of desire and expectancies changed over time with treatment, we used a within-person approach to examine whether daily variation in expectancies and desire to drink interact with topiramate treatment and genotype to predict nighttime drinking levels. In contrast to the previous analysis (Kranzler et al., 2014b), here we focus on whether alcohol expectancies and desire to drink moderate the effects of topiramate on drinking. Results showed a 3-way interaction of daily expectancies with genotype and medication, such that the protective effect of topiramate on nighttime drinking among rs2832407*C-allele homozygotes was decreased on days characterized by relatively high levels of anticipated positive effects of alcohol. There was no moderating effect of desire to drink or negative alcohol expectancies. Thus, there is specific moderation of the effects of topiramate by both genotype and cognitive process.