Antisocial behaviour in young people with ADHD: Identifying risk pathways

反社会行为是一个重大的临床和社会问题。然而，反社会行为有许多不同的类型和原因。有一类儿童在成年后表现非常糟糕，他们在童年时期表现出反社会行为，并伴有注意力不集中、多动和冲动（ADHD）等问题。虽然遗传、家庭和社会因素都有助于反社会行为，但遗传因素似乎对这一亚群尤为重要。有趣的是，一种影响一种叫做COMT的大脑酶的基因变异被发现与这类儿童的反社会行为有关。通常情况下，我们需要对这样的发现保持谨慎，但这种联系现在已经在世界各地的5个不同样本中得到了报道。因此，现在是时候了解这种基因是如何影响反社会儿童这一亚群的，这样我们就可以找到更好的治疗方法。不幸的是，针对这些儿童的现有治疗方法似乎无法长期发挥作用。我们对这种基因如何增加风险有一些想法，因为它与正常人的大脑功能和情绪有关。我们所做的一些探索性工作表明，减少对情绪刺激的反应可能很重要。然而，为了准确地测试这一点，我们需要让受影响的孩子来到我们的实验室，这样我们就可以通过观察这些孩子在特定任务中的表现来适当地测量情绪和大脑功能。这项提议的目的是对274名患有多动症的男性青少年进行测试，以检查COMT基因变异是否会通过情绪或情感途径增加早发性反社会行为的风险。我们将以这样一种方式进行研究，一旦我们有了结果，我们也将能够进行涉及大脑成像的研究，以更直接的方式发现受影响者的大脑中发生了什么。

Antisocial behaviour is a major clinical and societal problem. However, there are many different types and causes of antisocial behaviour. One subgroup of children that shows very poor outcomes in adult life consists of children who show antisocial behaviour in childhood accompanied by problems with inattention, hyperactivity and impulsiveness (ADHD). Although inherited, family and social factors all contribute to antisocial behaviour, inherited factors seem to be especially important for this subgroup. Interestingly, a gene variant that affects a brain enzyme called COMT has been found to be associated with antisocial behaviour in this subgroup of children. Usually, there is a need to be cautious about such findings, but this link has now been reported in 5 different samples across the world. It is therefore time to understand how this gene affects this subgroup of antisocial children so we can get clues for better types of treatment. Unfortunately, existing treatments for these children do not seem to work in the longer term. We have some ideas as to how this gene might increase risk, because it has been linked to brain function and emotions in normal individuals. Some exploratory work that we have done suggests that reduced reaction to emotional stimuli might be important. However, to accurately test this we need to ask affected children to come into our laboratory so we can properly measure emotions and brain function by seeing how well these children do on specific tasks. The aim of this proposal is to test 274 male adolescents with ADHD to examine whether the COMT gene variant increases the risk of early onset antisocial behaviour through emotional or affective pathways. We will set the study up in such a way that once we have results, we will also be able to undertake research involving brain imaging to find out in a more direct way what happens in the brains of those affected.