Department of Psychology, University of California, Los Angeles, California 90095-1563, USA.
Biol Psychiatry. 2010 Mar 1;67(5):487-92. doi: 10.1016/j.biopsych.2009.10.021. Epub 2009 Dec 14.
Across multiple mental health-related measures, a polymorphism (5-HTTLPR) within the promoter of the serotonin transporter gene has been associated with differential psychological sensitivity to stressful experiences. Yet, the specific mechanisms by which this polymorphism contributes to risk for psychological dysfunction is unclear. Therefore, we investigated cortisol reactivity to psychosocial stress as a potential intermediate phenotype that might predispose to such risk.
A psychologically healthy sample of 182 young adults were genotyped for the 5-HTTLPR. Each participant delivered a speech and performed mental arithmetic in one of three audience conditions: a critical evaluative audience, a supportive evaluative audience, or no audience. Salivary cortisol was sampled at baseline and at 20, 40, and 75 min after stressor onset.
The two evaluative audience conditions elicited similar, significant increases in cortisol that were significantly greater than in the no audience control. Together, the evaluative audience conditions revealed a significant relationship between cortisol reactivity and the 5-HTTLPR, with the short/short genotype showing the greatest reactivity. Internal analyses revealed that the 5-HTTLPR was significantly associated with cortisol reactivity in the negative audience condition only, suggesting that short/short individuals might be especially vulnerable to social threat.
The short/short genotype of the 5-HTTLPR is associated with greater cortisol reactivity to social threat. When short/short individuals experience stressful life events, they might be at greater risk for the adverse psychological and physical health consequences associated with heightened cortisol exposure.
在多种与心理健康相关的指标中，5-羟色胺转运体基因启动子中的一个多态性（5-HTTLPR）与对压力体验的心理敏感性差异有关。然而，这种多态性如何导致心理功能障碍的风险尚不清楚。因此，我们研究了皮质醇对心理社会应激的反应作为一种潜在的中间表型，这种中间表型可能会导致这种风险。
对 182 名心理健康的年轻成年人进行 5-HTTLPR 基因分型。每个参与者在三种观众条件下发表演讲并进行心算：批评性评估观众、支持性评估观众或无观众。在应激源开始后的 20、40 和 75 分钟时采集唾液皮质醇样本。
两种评估性观众条件均引起皮质醇的相似、显著增加，且明显大于无观众对照。评估性观众条件一起显示出皮质醇反应性与 5-HTTLPR 之间的显著关系，短/短基因型表现出最大的反应性。内部分析表明，只有在负面观众条件下，5-HTTLPR 与皮质醇反应性显著相关，这表明短/短个体可能特别容易受到社会威胁。
5-HTTLPR 的短/短基因型与对社会威胁的皮质醇反应性增加有关。当短/短个体经历压力生活事件时，他们可能面临更大的风险，因为皮质醇暴露增加会导致不良的心理和身体健康后果。
