A multi-site study of the genetics of child anxiety and predictors of treatment response

背景：焦虑是一种常见的、使人衰弱的问题，一直持续到成年，并与各种各样的困难有关。那些在童年时期首次经历焦虑症的人表现出最差的长期结果。例如，这些孩子比其他孩子更有可能缺课，因为他们错过了社交和学术发展的机会。虽然很明显，遗传和环境影响在焦虑的发展中都很重要，但我们对所涉及的具体因素和机制知之甚少。人们对抑郁症的基因了解得更多，抑郁症在基因上与焦虑相似，从而为焦虑的基因研究提供了几个有用的起点。最后，虽然儿童焦虑症最常用的治疗方法是？谈话治疗?被称为认知行为疗法（CBT），大约五分之二的患者没有好转。年龄较小的女孩似乎更有可能反应良好，而那些症状更严重或父母也有焦虑和/或抑郁问题的女孩则反应不佳。这两个因素表明，这些儿童可能有更重的焦虑基因负荷，这意味着基因可能对治疗反应有影响。研究计划：本研究将考虑有理论和实验证据表明与焦虑或抑郁有关的基因。例如，与血清素系统有关的基因，是百忧解等常见抗抑郁药的目标，已被证明在抑郁症的发展和药物治疗中发挥作用，并在一些与焦虑相关的特征中发挥作用，如儿童的极度害羞。我们将考虑这些和其他选定的基因在儿童焦虑的发展和治疗中的作用。从2500名患有临床焦虑症的儿童样本中收集的DNA（遗传物质），其中大多数正在接受CBT治疗，将用于检查两个核心问题。首先，是否存在与儿童焦虑症相关的特定基因？其次，我们能否根据年龄、性别、焦虑严重程度、父母心理健康状况和特定基因等因素预测治疗结果？识别与焦虑症发展相关的基因可以使有针对性的预防工作成为可能，而了解与治疗反应相关的基因可以使个性化的治疗方案成为可能。

Background: Anxiety is a common and debilitating problem for our youth, shows continuity into adulthood and is associated with wide-ranging difficulties. Those individuals who first experience an anxiety disorder during their childhood show the poorest long-term outcomes. For example, such children are much more likely than other children to be absent for significant portions of their schooling missing out on the opportunity for both social and academic development. Whilst it is clear that both genetic and environmental influences are important in the development of anxiety, we know relatively little about the specific factors and mechanisms involved. More is known about the genetics of depression, which has been shown to be genetically similar to anxiety, thus providing several useful starting points for genetic studies of anxiety. Finally, whilst child anxiety is most commonly treated using a ?talking treatment? called cognitive-behaviour therapy (CBT), around two-fifths of patients do not improve. Younger girls seem more likely to respond well, whereas those with worse symptoms or whose parents also have difficulties with anxiety and/or depression respond less well. These two factors suggest that these children may have a heavier genetic loading for anxiety, implying a possible genetic influence on treatment response. Research Plan: Genes for which there is theoretical and experimental evidence for involvement in anxiety or depression will be considered in this study. For example, genes involved in the serotonin system, the target of common anti-depressants such as Prozac, have been shown to play a role in the development and pharmacological treatment of depression, and in several anxiety-related characteristics such as extreme shyness in children. We will consider the role of these and other selected genes in the development and treatment of child anxiety. DNA (genetic material) collected from a sample of 2500 children with clinical anxiety, most of whom are being treated with CBT will be used to examine two core questions. First, are there specific genes associated with childhood anxiety disorders? Second, can we predict treatment outcome from factors such as age, sex, severity of anxiety, parental mental health and specific genes? Identifying genes relevant to the development of anxiety disorders could enable targeted prevention work, whilst knowledge of genes relevant to treatment response could allow for individualised treatment programmes.