Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Soc Cogn Affect Neurosci. 2013 Jun;8(5):499-508. doi: 10.1093/scan/nss020. Epub 2012 Feb 15.
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.
在将外显行为谱（成瘾、冲动、冒险、寻求新奇特质）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，结果不一致或为零，这可能源于个体对突出环境调节剂（基因×环境相互作用）的可变暴露。在这里，我们报告说，对即时、较小奖励的相对偏好超过对延迟时间的较大奖励（延迟折扣），这是冲动决策的行为表型，在 546 名中年社区志愿者中，DRD4 基因型与儿童社会经济地位（SES）的相互作用而有所不同。独立于年龄、性别、成年 SES 和智商，在那些既来自 SES 明显较低的家庭（父母教育程度和职业等级较低）又携带 DRD4 7 重复等位基因的参与者中，与具有不同 DRD4 基因型的类似抚养的对应者相比，他们对未来奖励的折扣更为陡峭。然而，在没有儿童社会经济劣势的情况下，携带 7 重复等位基因的参与者对未来奖励的折扣则不那么陡峭。这种 DRD4 基因型与时间折扣的双向关联，受参与者早期生活环境的影响，符合最近提出的基因×环境相互作用的发展模型（“差异易感性”），该模型假设对不利和有益的环境影响具有基因调节的敏感性。
