Persistence and emergence of ADHD in young adulthood: Unravelling aetiology using genetics in a population-based longitudinal cohort

成年早期 ADHD 的持续存在和出现：在基于人群的纵向队列中利用遗传学揭示病因学

• 批准号: MR/P014100/1
• 负责人: Jessica Agnew-Blais
• 金额: $ 40.08万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FP014100%2F1
• 关键词: Persistence; emergence; ADHD; young; adulthood

While ADHD was historically thought to only affect children, it is now recognized that it may continue into adulthood. Studies identify about 2.5-5% of adults as having ADHD, which is associated with poor outcomes including unemployment, substance abuse, and even higher mortality. I recently conducted a study that found not only may ADHD continue into adulthood, but the disorder may also newly begin in young adulthood. This is a novel finding, as ADHD is currently understood to begin in childhood. My findings are supported by results from two other recent studies in Brazil and New Zealand that also identified late-onset ADHD groups. Currently, little is known about those adults who did not have ADHD in childhood but developed it in adulthood. Who are individuals with late-onset ADHD? Did they have a disposition to develop ADHD as children, but grew up in very supportive households that masked their disorder until later life? Or do these people not have ADHD in adulthood, but rather another disorder with symptoms that could look like ADHD?Genetic studies can provide crucial insights in answering such questions about late-onset ADHD, and indeed broader questions about ADHD in young adulthood. One way to understand how late-onset ADHD might be similar or different to childhood ADHD is to investigate whether people with late-onset ADHD have higher levels of risk genes for childhood ADHD. If so, this would support the idea that people with late-onset ADHD would have shown ADHD in childhood, but the disorder was perhaps masked by a supportive family environment. In contrast, if people with late-onset ADHD do not have more risk genes for ADHD, but rather for other mental health disorders, this would suggest that late-onset ADHD may be explained by other mental health problems with symptoms similar to ADHD.The age at which ADHD symptoms may appear varies broadly from person to person, with some individual's symptoms beginning in infancy, while for others symptoms may not emerge until adolescence or later. I will examine how genes affect whether an individual develops either childhood or adult-onset ADHD, as well as how genes affect when ADHD symptoms first begin across a range of ages over development. It is not known whether some genes may increase risk for a very early onset of ADHD (e.g. infancy) whereas others increase risk for later onset (i.e. late childhood), and whether genes that affect when ADHD begins are different from those that affect whether an individual develops ADHD in the first place. Genes do not act alone to increase risk for ADHD. Rather, people's genes interact with their environment to influence the development of ADHD. For example, even people with many ADHD risk genes may not develop the disorder if they grow up in a protective environment; likewise, people with few ADHD risk genes might develop the disorder if they grow up in adverse environments. I will explore aspects of the social and family environment that could protect against or exacerbate genetic risk for ADHD. One pathway through which the environment can influence risk of ADHD is through epigenetics changes, which can turn genes 'on and off'. In this way, two identical twins who share 100% of their DNA may express different genes depending on epigenetic variations. I will compare epigenetic differences among twin pairs in which one twin has late-onset ADHD and the other does not, to identify biological changes that may be markers of young adult ADHD. To-date, the majority of ADHD research has assumed that all cases of adult ADHD began in childhood. However, I and other researchers have recently found this may often not be the case. Understanding how, why and when adult ADHD may develop is a crucial question and has broad implications for the diagnosis and treatment of adult ADHD.

虽然历史上认为ADHD只影响儿童，但现在人们认识到它可能会持续到成年。研究发现，约有2.5-5%的成年人患有ADHD，这与失业、药物滥用、甚至更高的死亡率等不良后果有关。我最近进行了一项研究，发现ADHD不仅可能会持续到成年，而且这种疾病也可能在年轻时新开始。这是一个新的发现，因为目前人们认为ADHD从童年就开始了。我的发现得到了最近在巴西和新西兰进行的另外两项研究的结果的支持，这两项研究也确定了迟发性ADHD群体。目前，对于那些在童年没有ADHD但在成年后发展为ADHD的成年人，人们知之甚少。谁是晚发性多动症患者？他们是否在孩提时代就有患上ADHD的倾向，但在非常支持他们的家庭长大，这些家庭一直掩盖着他们的疾病，直到晚年？或者，这些人在成年后不是患有ADHD，而是另一种症状看起来像ADHD的疾病？遗传学研究可以提供至关重要的见解，来回答关于晚发性ADHD的问题，甚至是关于年轻人ADHD的更广泛的问题。要了解迟发性ADHD与儿童期ADHD的相似或不同之处，一种方法是调查迟发性ADHD患者是否具有更高水平的儿童ADHD风险基因。如果是这样的话，这将支持这样一种观点，即晚发型ADHD患者在童年时就会表现出ADHD，但这种障碍可能被支持性的家庭环境掩盖了。相比之下，如果迟发性ADHD患者没有更多的ADHD风险基因，而是其他精神健康疾病的风险基因，这表明迟发性ADHD可能是由其他具有类似ADHD症状的精神健康问题来解释的。出现ADHD症状的年龄因人而异，有些人的症状从婴儿期就开始了，而另一些人的症状可能要到青春期或更晚才出现。我将研究基因是如何影响一个人是在儿童时期还是成年后患上ADHD，以及当ADHD症状在不同年龄段的发育过程中首次出现时，基因是如何影响的。目前尚不清楚一些基因是否会增加早发性多动症(如婴儿期)的风险，而另一些基因则会增加晚发性多动症(如儿童期晚期)的风险，以及影响多动症开始时间的基因是否与最初影响个人是否患上多动症的基因不同。基因并不是单独作用于增加ADHD风险的。相反，人们的基因与他们的环境相互作用，影响ADHD的发展。例如，即使是具有许多ADHD风险基因的人，如果他们在保护性环境中长大，也可能不会患上这种疾病；同样，如果他们在不利的环境中长大，几乎没有ADHD风险基因的人可能会患上这种疾病。我将探索社会和家庭环境中可能预防或加剧ADHD遗传风险的方面。环境影响ADHD风险的一个途径是通过表观遗传学变化，这种变化可以打开和关闭基因。通过这种方式，两个拥有100%DNA的同卵双胞胎可能会根据表观遗传变异表达不同的基因。我将比较双胞胎之间的表观遗传学差异，其中一对双胞胎患有晚发性ADHD，另一对没有，以确定可能是青壮年ADHD标志的生物学变化。到目前为止，大多数ADHD研究都假设所有成人ADHD病例都始于童年。然而，我和其他研究人员最近发现，情况往往并非如此。了解成人ADHD是如何、为什么以及何时发生的是一个至关重要的问题，对成人ADHD的诊断和治疗具有广泛的意义。

项目成果

Young adult mental health and functional outcomes among individuals with remitted, persistent and late-onset ADHD.

• DOI: 10.1192/bjp.2018.97
• 发表时间: 2018-09
• 期刊: The British journal of psychiatry : the journal of mental science
• 作者: Agnew-Blais JC;Polanczyk GV;Danese A;Wertz J;Moffitt TE;Arseneault L
• 通讯作者: Arseneault L

Childhood comorbidity and parental mental health problems appear to be associated with ADHD persistence.

儿童期合并症和父母的心理健康问题似乎与多动症的持续存在有关。

• DOI: 10.1136/eb-2017-102656
• 发表时间: 2017
• 期刊: Evidence-based mental health
• 影响因子: 5.2
• 作者: Agnew-Blais J

Are changes in ADHD course reflected in differences in IQ and executive functioning from childhood to young adulthood?

• DOI: 10.1017/s0033291719003015
• 发表时间: 2020-12-01
• 期刊: PSYCHOLOGICAL MEDICINE
• 影响因子: 6.9
• 作者: Agnew-Blais, Jessica C.;Polanczyk, Guilherme, V;Arseneault, Louise
• 通讯作者: Arseneault, Louise

Polygenic Risk and the Course of Attention-Deficit/Hyperactivity Disorder From Childhood to Young Adulthood: Findings From a Nationally Representative Cohort.

• DOI: 10.1016/j.jaac.2020.12.033
• 发表时间: 2021-09
• 期刊: Journal of the American Academy of Child and Adolescent Psychiatry
• 影响因子: 13.3
• 作者: Agnew-Blais JC;Belsky DW;Caspi A;Danese A;Moffitt TE;Polanczyk GV;Sugden K;Wertz J;Williams BS;Lewis CM;Arseneault L
• 通讯作者: Arseneault L

A risk calculator to predict adult attention-deficit/hyperactivity disorder: generation and external validation in three birth cohorts and one clinical sample - ERRATUM.

一种预测成人注意力缺陷/多动症障碍的风险计算器：三个出生队列和一个临床样本 - 拨言的产生和外部验证。

• DOI: 10.1017/s2045796019000337
• 发表时间: 2019-07-03
• 期刊: Epidemiology and psychiatric sciences
• 影响因子: 8.1
• 作者: Caye A;Agnew-Blais J;Arseneault L;Gonçalves H;Kieling C;Langley K;Menezes AMB;Moffitt TE;Passos IC;Rocha TB;Sibley MH;Swanson JM;Thapar A;Wehrmeister F;Rohde LA
• 通讯作者: Rohde LA