Polymorphic variation in the dopamine D4 receptor predicts delay discounting as a function of childhood socioeconomic status: evidence for differential susceptibility.
Polymorphic variation in the dopamine D4 receptor predicts delay discounting as a function of childhood socioeconomic status: evidence for differential susceptibility.
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DOI：
10.1093/scan/nss020
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发表时间：
2013-06
影响因子：
4.2
通讯作者：
M. Sweitzer;I. Halder;J. Flory;A. Craig;P. Gianaros;R. Ferrell;S. Manuck
中科院分区：
文献类型：
--
作者：
M. Sweitzer;I. Halder;J. Flory;A. Craig;P. Gianaros;R. Ferrell;S. Manuck
在将外化谱行为（成瘾、冲动、冒险、寻求新奇特征）与编码多巴胺 D4 受体 (DRD4) 的基因中常见长度多态性的 7 重复等位基因的存在相关联的研究中，结果不一致或无效，可能源于个体对显着环境调节剂的不同暴露（基因 × 环境相互作用）。在这里，我们报告了在 546 名中年社区志愿者中，对即时、较小奖励相对于较大奖励的相对偏好（延迟贴现），这是冲动决策的行为内表型，因 DRD4 基因型与儿童社会经济地位 (SES) 的相互作用而变化。与年龄、性别、成年社会经济地位和智商无关，在社会经济地位明显较低（父母教育程度和职业等级较低）的家庭中长大并携带DRD4 7重复等位基因的参与者，与其他DRD4基因型的类似抚养者相比，对未来奖励的折扣更大。然而，在没有童年社会经济劣势的情况下，携带 7 次重复等位基因的参与者对未来奖励的折扣幅度较小。 DRD4 基因型与时间折扣的这种双向关联，以参与者的早期生活环境为条件，符合最近提出的基因×环境相互作用的发育模型（“差异易感性”），该模型假定基因调节对不利和有益环境影响的敏感性。
Inconsistent or null findings among studies associating behaviors on the externalizing spectrum--addictions, impulsivity, risk-taking, novelty-seeking traits--with presence of the 7-repeat allele of a common length polymorphism in the gene encoding the dopamine D4 receptor (DRD4) may stem from individuals' variable exposures to prominent environmental moderators (gene × environment interaction). Here, we report that relative preference for immediate, smaller rewards over larger rewards delayed in time (delay discounting), a behavioral endophenotype of impulsive decision-making, varied by interaction of DRD4 genotype with childhood socioeconomic status (SES) among 546 mid-life community volunteers. Independent of age, sex, adulthood SES and IQ, participants who were both raised in families of distinctly low SES (low parental education and occupational grade) and carried the DRD4 7-repeat allele discounted future rewards more steeply than like-reared counterparts of alternate DRD4 genotype. In the absence of childhood socioeconomic disadvantage, however, participants carrying the 7-repeat allele discounted future rewards less steeply. This bidirectional association of DRD4 genotype with temporal discounting, conditioned by participants' early life circumstances, accords with a recently proposed developmental model of gene × environment interaction ('differential susceptibility') that posits genetically modulated sensitivity to both adverse and salubrious environmental influences.