Center for Psychobiology and Behavioral Medicine, University of Giessen, Department of Psychology, Otto-Behaghel-Str. 10, D-35394 Giessen, Germany.
Behav Brain Res. 2011 Jan 1;216(1):53-8. doi: 10.1016/j.bbr.2010.07.003. Epub 2010 Jul 8.
Catecholamines modulate endocrine stress reactivity by affecting regulatory influences of extra-hypothalamic brain structures on hypothalamus-pituitary-adrenal (HPA)-axis. Therefore, we aimed to investigate combined effects of functional allelic variations that affect dopamine availability in both cortical (COMT Val¹⁵⁸Met polymorphism) and subcortical (DAT1 VNTR) brain regions on HPA-axis reactivity to psychosocial stress. By using a standardized laboratory stress task (public speaking) we obtained saliva cortisol samples during stress exposure and an extended recovery period in 100 healthy male adults. We report for the first time significant epistasis between COMT Val¹⁵⁸Met and DAT1 VNTR on cortisol response patterns. Subjects homozygous for both the Met¹⁵⁸ and the 10-repeat allele of DAT1 VNTR were characterized by markedly elevated cortisol reactivity and impaired stress recovery compared to all other groups. Our results indicate a crucial role of functional genetic variants within the dopaminergic system in the modulation of HPA-axis response patterns and highlight the need to investigate combined effects of specific candidate genes on stress-related endophenotypes.
儿茶酚胺通过影响下丘脑-垂体-肾上腺（HPA）轴上的下丘脑外脑结构对内分泌应激反应的调节作用来调节。因此，我们旨在研究影响皮质（COMT Val158Met 多态性）和皮质下（DAT1 VNTR）脑区多巴胺可利用性的功能等位基因变异对 HPA 轴对应激的反应性的联合作用。通过使用标准化的实验室应激任务（公开演讲），我们在 100 名健康男性成年人的应激暴露期间和延长的恢复期获得唾液皮质醇样本。我们首次报道 COMT Val158Met 和 DAT1 VNTR 之间存在显著的上位性，这对皮质醇反应模式有影响。与其他所有组相比，DAT1 VNTR 的 Met158 和 10 重复等位基因纯合的受试者的皮质醇反应性明显升高，应激恢复受损。我们的结果表明，多巴胺能系统内的功能性遗传变异在调节 HPA 轴反应模式方面起着关键作用，并强调需要研究特定候选基因对与应激相关的内表型的联合作用。
