Neurodevelopmental Perspectives on ADHD

描述（由申请人提供）：这项竞争性更新申请是基于一个新的模型，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是由于调节功能的主要缺陷，最有可能是皮层下的起源，在个体发育的早期就存在，在整个生命周期中保持相对静止，与普遍存在的，尽管高度可变的，症状和损害的减少通常在发育过程中出现无关。我们假设，在整个发育过程中经常看到的症状和损伤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。使用大量的“多动/注意力不集中”和典型发展的对照儿童样本，这些儿童在3-4岁时被招募，并从那时起每年进行一次评估，本研究将检查学龄期ADHD症状的轨迹，以确定ADHD严重程度的变化与调节和执行功能的发展之间的关系。儿童将在8至12岁之间使用临床和神经心理学测量每年进行全面重新评估。此外，这些年度评估将辅以半年一次的家长和老师对ADHD症状严重程度和家庭和学校环境损害的评分，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。这个项目的主要目的是测试这样一个假设，即多动症症状的减轻通常与“自上而下”的执行过程的发展有关，但“自下而上”的调节功能将继续受损，无论临床改善如何。如果这一假设得到证实，它可能对新型治疗干预措施的发展产生重大影响。

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.