IMAGINE-2: Stratifying Genomic Causes of Intellectual Disability by Mental Health Outcomes in Childhood and Adolescence

在英格兰，有100多万人患有学习障碍，其中四分之一是学龄儿童。大多数中度到重度智力残疾(ID)都有遗传原因。为了识别这些遗传风险，英国国民健康保险制度现在正在对有严重发育迟缓的儿童进行例行DNA筛查。被告知孩子的ID是由基因变化引起的，这对父母来说是有价值的。但是，目前，我们很少使用这些信息来为行为和教育问题的最佳管理提供建议，或者降低心理健康状况不佳的风险。我们的研究旨在填补这一知识空白。我们的Imagine-ID研究项目始于2014年。截至2019年，我们招募了近3500个英国家庭，这些家庭的孩子因遗传原因而患有ID。通过在线采访、问卷调查和与家庭面对面的会面，我们全面了解了这些孩子的优势和劣势。我们发现，出现严重行为和情绪问题的风险比之前认识到的要大得多。虽然普通人群中患有ID的儿童患此类问题的可能性是普通人的6倍，但如果残疾是由遗传原因造成的，风险则要高出30倍以上。我们还发现，遗传风险是遗传的孩子比那些偶然发生同等变化的孩子有更严重的情感和行为问题。也许携带这种基因异常的父母可能会受到轻微的影响，尽管他们的残疾程度不同于他们的孩子？与参与我们研究计划的其他家庭相比，他们更有可能生活在拥挤、住房质量差和失业的不利环境中。不利的社会环境会造成育儿困难，并加剧孩子的问题。我们需要更多地了解这些重要的脆弱性。如果我们更多地了解导致他们陷入困境的过程，就可以更快地确定处于危险中的家庭，并在未来更有效地提供支持。我们的新研究将解决这些问题。我们将在最初评估5年后对所有参与者进行跟踪和访谈，以问：第一，我们在之前的研究中发现的心理健康问题是否持续存在？第二，如果他们坚持或改善了，自我们第一次见到这些家庭以来，医疗、教育和环境因素发生了哪些变化？我们在第一项研究中看到的大多数儿童年龄在6岁到13岁之间。在我们的后续行动中，许多人将进入青春期或成年早期。在这个时候，一些心理健康问题的风险会变得更大。我们将努力发现年轻人的行为和情绪调整，或他们新出现的精神健康障碍的风险，是否受到他们的家庭在过去5年中接受的教育、医疗或其他支持的影响。我们将寻找线索，找出结果最好和最差的儿童。Imagine-ID中超过三分之一的儿童患有自闭症谱系障碍。四分之一的人患有ADHD，而同样比例的人要么有严重的焦虑，要么有严重的挑战性行为。这对这些孩子的教育进步有什么影响？当地的医疗和精神卫生服务部门在多大程度上承认和治疗了这些疾病？为了收集这些信息，我们将补充我们在后续访谈过程中从父母那里学到的东西，这些记录来自全国收集的关于儿童教育(来自国家学生数据库)和关于他们的病史(来自NHS医院事件统计数据库)的记录。我们还将使用医疗记录中的信息来更多地了解ID与遗传原因和癫痫之间的密切联系，在Imagine-ID队列中，高达70%的儿童会受到影响

In England, there are over a million people with learning disabilities, a quarter of whom are children of school age. Most moderate to severe intellectual disability (ID) has a genetic cause. In order to identify those genetic risks, the NHS is now routinely screening the DNA of children who have significant developmental delays. Being informed that their child's ID is caused by a genetic change is of value to parents. But, at present, we can rarely use that information to advise on best management of behavioural and educational issues, or to reduce the risk of poor mental health outcomes. Our study aims to fill that gap in knowledge. Our IMAGINE-ID programme of research began in 2014. By 2019 we had recruited nearly 3500 UK families whose child has ID due to a genetic cause. Using a combination of online interviews, questionnaires, and face-to-face meetings with families, we built up a comprehensive picture of those children's strengths and weaknesses. We discovered there was a far greater risk of severe behavioural and emotional problems than was previously recognised. Whilst children with ID from the general population are about six times as likely to have problems of this nature, the risk is over thirty times greater if the disability has a genetic cause. We also discovered that children whose genetic risk was inherited had more severe emotional and behavioural problems than those in which the equivalent change occurred by chance. Perhaps parents who carry the genetic anomaly could be mildly affected by it, although they do not share the same degree of disability as their child? They are more likely than other families participating in our research programme to live in disadvantaged circumstances with overcrowding, poor quality housing, and unemployment. Adverse social circumstances would contribute to parenting difficulties and exacerbate their child's problems. We need to learn more about these important points of vulnerability. Families at risk could be identified sooner, and supported more effectively in future, if we understood more about the processes that led to their difficulties. These questions will be addressed by our new research. We will follow up and interview all participants 5 years after our initial assessment, to ask: first, have the mental health issues we uncovered in the previous study persisted? Second, if they have persisted, or improved, what are the medical, educational and environmental factors that have changed since we first met those families? Most children we saw in the first study were between 6 and 13 years of age. During our follow-up, many will be entering adolescence or early adulthood. That is a time when the risks of some mental health problems become substantially greater. We will be endeavouring to discover whether the young person's behavioural and emotional adjustment, or their risk of emerging mental health disorders, is influenced by the educational, medical or other support their families have received over the past 5 years. We will be looking for clues that pinpoint those children with the best and worst outcomes.More than one in three children in IMAGINE-ID had an Autism Spectrum Disorder. A quarter had ADHD, and a similar proportion had either severe anxiety or serious challenging behaviour. What was the impact on those children's educational progress? To what extent were those conditions recognised and treated by their local medical and mental health services? To gather that information, we will supplement what we learn from parents in the course of our follow-up interviews with nationally collected records on the children's education (from the National Pupil Database) and on their medical history (from the NHS Hospital Episode Statistics Database). We will also use information from medical records to learn more about the strong association between ID with a genetic cause and seizures, which affect up to 70% of children in the IMAGINE-ID cohort