Klaus K, Vaht M, Pennington K, Harro J
School of Psychology, University of Lincoln, Brayford Wharf, Lincoln, LN5 7AT, England, UK; MRC Cognition and Brain Sciences Unit, University of Cambridge, 15 Chaucer Road, Cambridge, CB3 0HH, England, UK.
Estonian Genome Centre, Institute of Genomics, University of Tartu, Riia 23b, 51010, Tartu, Estonia.
Behav Brain Res. 2021 Apr 9;403:113131. doi: 10.1016/j.bbr.2021.113131. Epub 2021 Jan 11.
Previous research has shown that dopaminergic dysregulation and early life stress interact to impact on aspects of impulse control. This study aimed to explore the potentially interactive effects of the rs6277 polymorphism of the dopamine D2 receptor gene (DRD2), stressful or supportive environment and sex on behavioural and self-reported measures of impulsivity, as well as alcohol use - a condition characterised by a deficit in impulse control. The sample consisted of the younger cohort (n = 583) of the longitudinal Estonian Children Personality, Behaviour and Health Study. The results showed that the CC homozygotes (suggested to have decreased striatal D2 receptor availability) who had experienced stressful life events (SLE) or maltreatment in the family prior to age 15 showed higher self-reported maladaptive impulsivity at age 15. The genotype-SLE interaction and further association with sex was also evident in the frequency of alcohol use at age 15. Lack of warmth in the family contributed to significantly higher levels of thoughtlessness and more frequent alcohol use in CC carriers at age 25, whereas family support was associated with lower thoughtlessness scores in CC males, which may suggest a protective effect of supportive family environment in this group. Together the findings suggest that DRD2 rs6277 polymorphism, in interaction with environmental factors experienced in childhood and youth may affect facets of impulsivity. Future work should aim to further clarify the sex and age-specific effects of stressful and supportive environment on the development of neuronal systems that are compromised in disorders characterised by deficits in impulse control.
先前的研究表明，多巴胺能调节异常与早期生活压力相互作用，会影响冲动控制的各个方面。本研究旨在探讨多巴胺D2受体基因（DRD2）的rs6277多态性、压力或支持性环境以及性别对冲动行为和自我报告的冲动性测量指标，以及酒精使用（一种以冲动控制缺陷为特征的状况）的潜在交互作用。样本包括爱沙尼亚儿童性格、行为与健康纵向研究的较年轻队列（n = 583）。结果显示，在15岁之前经历过生活压力事件（SLE）或家庭虐待的CC纯合子（提示纹状体D2受体可用性降低）在15岁时自我报告的适应不良冲动性较高。15岁时饮酒频率方面，基因型与SLE的相互作用以及与性别的进一步关联也很明显。家庭缺乏温暖导致25岁时CC携带者的轻率程度显著更高且饮酒更频繁，而家庭支持与CC男性较低的轻率得分相关，这可能表明支持性家庭环境对该群体有保护作用。这些研究结果共同表明，DRD2 rs6277多态性与童年和青少年时期经历的环境因素相互作用，可能会影响冲动性的各个方面。未来的工作应旨在进一步阐明压力和支持性环境对以冲动控制缺陷为特征的疾病中受损的神经元系统发育的性别和年龄特异性影响。
