Department of Psychology, The University of Texas at Austin, Austin, TX 78756, USA.
Psychoneuroendocrinology. 2012 Jun;37(6):752-61. doi: 10.1016/j.psyneuen.2011.09.006. Epub 2011 Oct 5.
Striking parallels are observed when comparing the literature on the 5-HTTLPR of the serotonin transporter gene (SLC6A4) to the testosterone (T) literature on measures of stress reactivity and neural activity. Short (S) allele carriers and individuals higher in testosterone levels show exaggerated stress responses, amygdala hyperactivity, and reduction of amygdala-prefrontal cortex coupling when exposed to threat.
Three studies tested the hypothesis that higher T, S carriers would show increased cortisol responses to threat.
Supporting the hypothesis, a T × 5-HTTLPR interaction was obtained across all studies. Threats to status via social exclusion (Study 1), cognitive/perceptual failure (Study 2), and physical competence (Study 3) all produced elevated cortisol levels in S carriers with higher T levels. An unexpected result was that 5-HTTLPR long (L) allele homozygotes with higher T showed lower cortisol levels in response to threat-a pattern of response that closely parallels that reported for psychopathic individuals. Finally, combining effect sizes across studies showed that the likelihood that these effects were due to Type 1 errors was quite low.
What emerges from these studies is a novel yet reliable, and synergistic relationship between 5-HTTLPR genotype and testosterone on stress reactivity, possibly conferring vulnerability for multiple neuropsychiatric disorders.
当比较 5-羟色胺转运蛋白基因（SLC6A4）的 5-HTTLPR 与睾酮（T）文献中关于应激反应和神经活动的测量时，会观察到惊人的相似之处。短（S）等位基因携带者和睾酮水平较高的个体在暴露于威胁时表现出过度的应激反应、杏仁核过度活跃以及杏仁核-前额叶皮层连接减少。
三项研究检验了这样一个假设，即较高的 T、S 携带者在受到威胁时会出现更高的皮质醇反应。
支持该假说，所有研究均获得了 T×5-HTTLPR 相互作用。通过社会排斥（研究 1）、认知/知觉失败（研究 2）和身体能力（研究 3）来威胁地位，都导致 S 携带者的皮质醇水平升高，而 T 水平较高。一个意外的结果是，5-HTTLPR 长（L）等位基因纯合子且 T 水平较高的个体在受到威胁时皮质醇水平较低，这种反应模式与报告的精神病态个体非常相似。最后，将研究的效应大小进行合并，表明这些效应归因于 Type 1 错误的可能性相当低。
这些研究的结果表明，5-HTTLPR 基因型与睾酮对应激反应的关系是新颖的、可靠的且协同的，这可能为多种神经精神障碍的易感性提供了依据。
