Neurodevelopmental Perspectives on ADHD

描述（由申请人提供）：该竞争性更新申请基于一种新模型，该模型假定部分不同的神经和认知机制参与注意力缺陷/多动障碍（ADHD）的病因学和发育轨迹。我们假设ADHD是由于调节功能的主要缺陷，最有可能是皮质下起源，存在于个体发育的早期，在整个一生中保持相对静态，并且与常见的，尽管高度可变的，症状和损伤的减少似乎经常超过发展无关。我们推测，在整个发展过程中经常看到的症状和损害的减少的变化是部分相关的程度，皮质介导的神经系统可以通过使用“自上而下”的执行控制来弥补这些早期的缺陷。使用大量的“多动/注意力不集中”和典型发育对照儿童的样本，这些儿童在3-4岁时被招募，并从那时起每年进行评估，本研究将检查学龄期ADHD症状的轨迹，以确定ADHD严重程度的变化与监管和执行功能随时间的发展之间的关系。每年将使用临床和神经心理学措施对8至12岁的儿童进行全面重新评估。此外，这些年度评估将由家长和教师每半年对家庭和学校环境中ADHD症状严重程度和损害程度的评级进行补充，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一假设，即ADHD症状的减少通常在发展中看到的是与“自上而下”的执行过程的发展，但“自下而上”的监管功能将继续受损，无论临床改善。如果这一假设得到证实，它可能对新的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.