Neurodevelopmental Perspectives on ADHD

描述(由申请人提供)：这项竞争性续签申请是基于一种新的模型，该模型假设部分不同的神经和认知机制参与了注意力缺陷/多动障碍(ADHD)的病因和发展轨迹。我们假设ADHD是由于调节功能的初级缺陷，最有可能是皮质下起源，存在于个体发育的早期，在整个生命周期中保持相对静止，与通常存在的尽管高度可变的症状和损害的减少无关，通常看起来像是过度发展。我们假设，在整个发育过程中经常看到的症状和损伤的减少的变化，部分与皮质介导的神经系统通过使用“自上而下”的执行控制来补偿这些早期缺陷的程度有关。这项研究使用了一个大样本，这些儿童在3-4岁时被招募，此后每年都会进行评估，利用这些儿童的大样本来研究ADHD症状在学龄期内的轨迹，以确定ADHD严重程度的变化与调控和执行功能随着时间的发展之间的关系。每年将使用临床和神经心理测量对8至12岁的儿童进行全面重新评估。此外，这些年度评估将辅之以半年一次的家长和教师对家庭和学校环境中ADHD症状严重程度和损害的评级，这将极大地促进我们对ADHD严重程度的个性化轨迹进行分析的能力。拟议项目的主要目的是检验这样一种假设，即在发育过程中通常可以看到的ADHD症状的减少与“自上而下”执行过程的发展有关，但无论临床情况如何改善，“自下而上”的调节功能仍将受损。如果这一假设得到证实，它可能会对新的治疗干预措施的发展产生重大影响。公共卫生相关性：这个项目旨在测试一个模型，该模型假设与ADHD严重程度的改善有关的特定机制与导致疾病的机制不同。如果我们的假设得到证实，它可能会对为这一高度受损的患者群体开发新的、长期的治疗干预措施产生重大影响。

DESCRIPTION (provided by applicant): This competitive renewal application is based on a novel model which posits that partially distinct neural and cognitive mechanisms are involved in the etiology and developmental trajectory of attention-deficit/hyperactivity disorder (ADHD). We hypothesize that ADHD is due to a primary deficit in regulatory functions, most probably of subcortical origin, that is present early in ontogeny, remains relatively static throughout the lifetime, and is unrelated to the commonly-present, although highly variable, diminution of symptoms and impairment often seem over development. We hypothesize that the variation in diminution of symptoms and impairment frequently seen throughout development is in part related to the degree to which cortically-mediated neural systems can compensate for these early deficits through the use of "top-down" executive control. Using a large sample of "hyperactive/inattentive" and typically-developing control children who were recruited when they were 3-4 years-old and evaluated annually since then, this study will examine trajectories of ADHD symptoms over the school-age years to determine the relationship between changes in ADHD severity and the development of regulatory and executive functions over time. Children will be comprehensively reevaluated annually using clinical and neuropsychological measures between the ages of 8 and 12 years. In addition, these annual assessments will be supplemented by semi-annual parent and teacher ratings of ADHD symptom severity and impairment in the home and school settings, which will greatly facilitate our ability to conduct analyses of individualized trajectories for ADHD severity. The primary aim of the proposed project is to test the hypothesis that the diminution of ADHD symptoms typically seen over development is associated with the development of "top-down" executive processes, but that "bottom-up" regulatory functions will remain impaired irrespective of clinical improvement. If this hypothesis is confirmed, it could have a significant impact on the development of novel treatment interventions. PUBLIC HEALTH RELEVANCE: This project is designed to test a model that posits specific mechanisms that are linked to the improvement of ADHD severity over development as distinct from those that cause the disorder. If our hypothesis is confirmed, it could have a significant impact on the development of novel, long-lasting, treatment interventions for this highly impaired group of patients.