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

IMAGINE-2：根据儿童和青少年时期的心理健康结果对智力障碍的基因组原因进行分层

• 批准号: MR/T033045/1
• 负责人: David Skuse
• 金额: $ 260.72万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT033045%2F1
• 关键词: IMAGINE; Stratifying; Genomic; Causes; Intellectual

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

在英国，有超过一百万人有学习障碍，其中四分之一是学龄儿童。大多数中度至重度智力残疾（ID）都有遗传原因。为了确定这些遗传风险，NHS现在正在定期筛查有明显发育迟缓的儿童的DNA。被告知他们孩子的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，我们很少能利用这些信息来建议对行为和教育问题的最佳管理，或减少不良心理健康结果的风险。我们的研究旨在填补这一知识空白。我们的IMAGINE-ID研究计划始于2014年。到2019年，我们已经招募了近3500个英国家庭，他们的孩子由于遗传原因而患有ID。通过在线访谈、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，严重的行为和情绪问题的风险比以前认识到的要大得多。虽然一般人群中患有ID的儿童患这种性质问题的可能性约为6倍，但如果残疾有遗传原因，则风险要高出30倍以上。我们还发现，遗传风险是遗传的儿童比那些偶然发生相同变化的儿童有更严重的情绪和行为问题。也许携带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与他们的孩子不同？他们比参与我们研究计划的其他家庭更有可能生活在过度拥挤、住房质量差和失业的不利环境中。不利的社会环境会造成养育子女的困难，并加剧其子女的问题。我们需要更多地了解这些重要的脆弱点。如果我们更多地了解导致处境危险的家庭陷入困境的过程，就可以更快地查明这些家庭，并在今后更有效地提供支助。我们的新研究将解决这些问题。我们将在初步评估后5年对所有参与者进行随访和访谈，询问：首先，我们在先前研究中发现的心理健康问题是否持续存在？第二，如果他们一直存在，或者有所改善，那么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至13岁之间。在我们的随访期间，许多人将进入青春期或成年早期。这是一些心理健康问题的风险大大增加的时候。我们将努力发现年轻人的行为和情绪调整，或他们出现精神健康障碍的风险，是否受到他们的家庭在过去5年中获得的教育，医疗或其他支持的影响。我们将寻找线索，找出最好和最差结果的孩子。在IMAGINE-ID中，超过三分之一的孩子患有自闭症谱系障碍。四分之一的人患有多动症，类似比例的人患有严重的焦虑或严重的挑战行为。对这些儿童的教育进展有什么影响？当地的医疗和精神卫生服务机构在多大程度上认识和治疗了这些疾病？为了收集这些信息，我们将补充我们在后续采访过程中从父母那里学到的东西，这些记录是全国收集的关于儿童教育的记录（来自全国学生数据库）和他们的病史（来自NHS医院事件统计数据库）。我们还将使用来自医疗记录的信息来了解更多关于遗传原因的ID与癫痫发作之间的密切联系，这影响了IMAGINE-ID队列中高达70%的儿童

项目成果

Intellectual disability and parents' mental health within the IMAGINE cohort study - how and when does genetic diagnosis matter?

IMAGINE 队列研究中的智力障碍和父母的心理健康 - 基因诊断如何以及何时发挥作用？

• DOI: 10.31234/osf.io/h67uz
• 发表时间: 2022
• 作者: Chi Z

Sleep disturbance as a transdiagnostic marker of psychiatric risk in children with neurodevelopmental risk genetic conditions

睡眠障碍作为神经发育风险遗传性疾病儿童精神风险的跨诊断标志

• DOI: 10.21203/rs.3.rs-1922492/v1
• 发表时间: 2022
• 作者: Chawner S

Behavioural and neurodevelopmental characteristics of SYNGAP1

SYNGAP1 的行为和神经发育特征

• DOI: 10.21203/rs.3.rs-3722732/v1
• 发表时间: 2023
• 作者: Bednarczuk N

Sleep disturbance as a transdiagnostic marker of psychiatric risk in children with neurodevelopmental risk genetic conditions.

• DOI: 10.1038/s41398-022-02296-z
• 发表时间: 2023-01-11
• 期刊: TRANSLATIONAL PSYCHIATRY
• 影响因子: 6.8
• 作者: Chawner, Samuel J. R. A.;Evans, Alexandra;Williams, Nigel J.;Owen, Michael;Hall, Jeremy;van den Bree, Marianne B. M.
• 通讯作者: van den Bree, Marianne B. M.

Neurodevelopmental dimensional assessment of young children at high genomic risk of neuropsychiatric conditions.

• DOI: 10.1002/jcv2.12162
• 发表时间: 2023-06
• 期刊: JCPP advances