Davies William, Humby Trevor, Kong Wendy, Otter Tamara, Burgoyne Paul S, Wilkinson Lawrence S
Behavioural Genetics Group, School of Psychology and Department of Psychological Medicine, School of Medicine, University of Cardiff, London, United Kingdom.
Biol Psychiatry. 2009 Aug 15;66(4):360-7. doi: 10.1016/j.biopsych.2009.01.001. Epub 2009 Feb 28.
Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder characterized by deficits in attention, increased motor impulsivity, and hyperactivity. Preliminary work in mice and humans has suggested the X-linked gene STS (which encodes the enzyme steroid sulfatase) as a mediator of attentional functioning and as a candidate gene for ADHD.
The effects of modulating the murine steroid sulfatase axis pharmacologically (through administration of the substrate dehydroepiandrosterone sulfate [DHEAS], 0-40 mg/kg, or acute inhibition of the enzyme by COUMATE, 10mg/kg) or genetically (through loss of the gene in 39,X(Y)*O mice) were assayed using the 5-choice serial reaction time task (5-CSRTT) a test of visuospatial attention and response control, and a locomotor activity paradigm.
DHEAS administration improved 5-CSRTT performance under attentionally demanding conditions, whereas steroid sulfatase inhibition impaired accuracy under the same conditions. Loss of Sts expression constitutively throughout development in 39,X(Y)*O mice resulted in deficits in 5-CSRTT performance at short stimulus durations and reduced anticipatory responding. Neither the pharmacologic nor the genetic manipulations affected basic locomotor activity.
These data provide converging evidence indicating a role for steroid sulfatase in discrete aspects of attentional functioning and are suggestive of a role in motor impulsivity. The findings provide novel insights into the neurobiology of attention and strengthen the notion of STS as a candidate gene for the attentional component of ADHD.
注意力缺陷多动障碍（ADHD）是一种复杂的神经发育障碍，其特征为注意力缺陷、运动冲动增加和多动。在小鼠和人类中的初步研究表明，X连锁基因STS（编码类固醇硫酸酯酶）是注意力功能的调节因子，也是ADHD的候选基因。
通过药理学方法（给予底物硫酸脱氢表雄酮[DHEAS]，0 - 40mg/kg，或用香豆酸急性抑制该酶，10mg/kg）或遗传学方法（通过39,X(Y)*O小鼠基因缺失）调节小鼠类固醇硫酸酯酶轴，使用5选串行反应时间任务（5-CSRTT）（一种视觉空间注意力和反应控制测试）和运动活动范式进行测定。
在注意力要求较高的条件下，给予DHEAS可改善5-CSRTT表现，而抑制类固醇硫酸酯酶在相同条件下会损害准确性。在39,X(Y)*O小鼠整个发育过程中持续缺失Sts表达，导致在短刺激持续时间下5-CSRTT表现出现缺陷，并减少预期反应。药理学和遗传学操作均未影响基本运动活动。
这些数据提供了一致的证据，表明类固醇硫酸酯酶在注意力功能的离散方面发挥作用，并提示其在运动冲动方面也有作用。这些发现为注意力的神经生物学提供了新的见解，并强化了STS作为ADHD注意力成分候选基因的概念。
