Characterising a newly-identified modulator of ADHD risk: the behavioural and neural functions of steroid sulfatase

患有注意力缺陷多动障碍(或更常见的ADHD)的儿童注意力不集中，多动，经常在行动时没有考虑到他们行为的后果。此外，他们经常焦虑、咄咄逼人，睡眠困难。因此，他们经常在教育和社会互动方面遇到困难，这可能会对他们的成年生活造成实质性和有害的连锁反应。许多研究表明，ADHD风险有很强的遗传基础。有趣的是，ADHD对男孩的影响似乎比女孩更常见，这意味着X或Y染色体上的一个或多个基因可能会影响患上这种疾病的易感性。最近在老鼠和人类身上的研究发现，X染色体上的一个基因可能会影响这种脆弱性。这种基因被称为STS，当它缺失时，男孩(或老鼠)容易出现与ADHD相关的症状。STS基因产生的蛋白质被称为类固醇硫酸酯酶。目前，关于类固醇硫酸酯酶在大脑中扮演的角色，特别是它如何影响注意力和冲动，人们知之甚少。由于对人脑功能的实验很难进行，而且范围有限，目前的建议将使用小鼠来确定类固醇硫酸酯酶操作对大脑发育和功能的影响，以期表征该蛋白质的功能。这些实验应该会给我们提供重要的线索，让我们知道ADHD受试者的大脑出了什么问题，这是找出如何补救它的关键的第一步。从我们的研究中获得的结果也可能最终帮助我们开发出治疗其他与注意力和冲动问题相关的常见和衰弱的疾病的方法，包括自闭症和精神分裂症。

Children with Attention Deficit Hyperactivity Disorder (or ADHD as it is more commonly known) have trouble concentrating, are hyperactive and often act without giving due thought to the consequences of their actions. Moreover, they are often anxious, aggressive and have problems sleeping. Consequently, they often have difficulties regarding education and social interactions, which can cause substantial and deleterious knock-on effects on their adult lives.Many studies have shown that ADHD risk has a strong genetic basis. Interestingly, ADHD seems to affect boys far more commonly than girls, implying that one or more genes on the X or Y chromosomes may influence vulnerability to developing the disorder. Recent work in mice and in humans has identified one gene on the X chromosome which may influence this vulnerability. The gene is called STS, and when it is absent boys (or mice) are prone to developing symptoms associated with ADHD. The protein made by the STS gene is called steroid sulfatase. Currently, little is known about the role steroid sulfatase plays in the brain, and in particular, how it might act to influence attention and impulsivity. As experiments on human brain function are difficult to perform and limited in their scope, the present proposal will use mice to identify the effects of steroid sulfatase manipulation on brain development and function, with a view to characterising the function of the protein. These experiments should give us important clues as to what is going wrong in the brains of subjects with ADHD, an essential first step to working out how we might remedy it. The results obtained from our studies might also ultimately help us to develop therapies against other common and debilitating disorders associated with attention and impulsivity problems, including autism and schizophrenia.