Armbruster D, Mueller A, Moser D A, Lesch K P, Brocke B, Kirschbaum C
Institute of Psychology II, Dresden University of Technology, Dresden, Germany.
Behav Neurosci. 2009 Dec;123(6):1288-95. doi: 10.1037/a0017615.
Genetic variation of the serotonin transporter (SCL6A4, 5-HTT) has been associated with fear- and anxiety-related behaviors, while a polymorphism in exon III of the D4 dopamine receptor gene (DRD4) has been linked to novelty seeking. The dopaminergic and the serotonergic neurotransmitter system have been found to modulate the amygdala-connected circuitries that are crucial in emotional modulation and response to fearful stimuli. Additionally, reactivity of amygdala-innervated effector systems is also essential for our understanding of anxiety-related behaviors. Here, we used the stress-induced activation of the hypothalamic-pituitary-adrenal axis to investigate the impact of 5-HTTLPR and DRD4 on the cortisol stress response in 84 healthy adults. Saliva cortisol was measured during and after the Trier Social Stress Test. We found a significant main effect of DRD4: Carriers of the 7R allele exhibited lower cortisol responses. Additionally, a DRD4 by 5-HTTLPR interaction emerged: 5-HTTLPR LA/LA homozygotes showed a lower cortisol response than did S or LG allele carriers but only if they possessed at least one copy of the DRD4 7R allele. The results point to independent and joint effects of these polymorphisms on stress responsivity.
血清素转运体（SCL6A4，5 - HTT）的基因变异与恐惧和焦虑相关行为有关，而D4多巴胺受体基因（DRD4）外显子III中的一个多态性与寻求新奇有关。多巴胺能和血清素能神经递质系统已被发现可调节与杏仁核相连的神经回路，这些回路在情绪调节和对恐惧刺激的反应中至关重要。此外，杏仁核支配的效应系统的反应性对于我们理解焦虑相关行为也至关重要。在此，我们利用下丘脑 - 垂体 - 肾上腺轴的应激诱导激活来研究84名健康成年人中5 - HTTLPR和DRD4对皮质醇应激反应的影响。在特里尔社会应激测试期间和之后测量唾液皮质醇。我们发现DRD4有显著的主效应：7R等位基因携带者表现出较低的皮质醇反应。此外，出现了DRD4与5 - HTTLPR的相互作用：5 - HTTLPR LA/LA纯合子比S或LG等位基因携带者表现出更低的皮质醇反应，但前提是他们至少拥有一份DRD4 7R等位基因。结果表明这些多态性对应激反应性有独立和联合效应。
