Neural mechanisms of risk and resilience in early childhood irritability (Diversity Supplement - E. Peterson)

项目总结/摘要 易怒，定义为当经历RDoC结构的挫折性非奖励时，愤怒的阈值降低， 也就是说，未能获得预期的奖励，是儿科精神病评估的最常见原因之一。 我们的工作表明，早期发现是至关重要的：如果在学龄前（3-6岁，一年级之前）易怒继续 进入学龄期（一年级后），因为它对大约50%的学龄前儿童易怒，如 持续的易怒会使孩子在一生中走上精神障碍的道路。因此，识别神经 儿童持续与缓解易怒的机制对于在最早阶段进行干预至关重要。 临床级联。易怒与奖励处理的异常有关，这可能导致更大的 当没有得到奖励时的挫折感。这种奖励处理漏洞可以通过更好的方法来改善。 抑制控制，其随成熟而正常增加。然而，奖励和奖励之间的相互作用 加工和抑制的易怒轨迹是未知的。研究神经系统的纵向变化 在这个发育阶段，神经回路是重要的，因为与奖赏和抑制相关的神经网络 发生实质性变化，可能最适合早期干预。我们的总体目标是确定 奖励和抑制相关的神经通路，表征幼儿期的持续性与缓解 易怒为此，拟议的项目将纵向表征神经和症状轨迹 学龄前儿童进入学校的机会。我们将收集与奖励和抑制控制相关的措施， 215名5-6岁儿童一年级前基线和24个月随访时的脑功能， 在每6个月随访时评估儿童易怒和抑制。全面评估儿童 （认知、气质、精神病理学）、父母（精神病理学）和背景因素（例如，为人父母， 压力源）也将在基线和24个月评估时进行评估。我们的核心假设是， 有奖励和抑制相关神经缺陷的儿童更容易持续易怒， 那些被赦免的人具体的目的是确定（1）奖励和抑制相关的神经元的并发贡献， 在每个年龄（学龄前，学龄）的易怒功能;（2）奖励的发展变化， 从幼儿期到幼儿中期的易怒轨迹的抑制相关神经机制;（3）幼儿期 奖励和抑制相关的神经预测易怒轨迹和未来的精神病理学;和（4） 儿童性别、父母精神病理学、养育方式和生活压力对这些脑行为的调节作用 协会.这项提案将通过揭示易怒风险和弹性的神经回路来推进该领域。 创新方面包括关注一个关键的年龄范围（5-6岁），以防止以后的障碍，多次 点成像和机器学习方法。我们的项目意义重大，因为它将为 针对易怒的精准医学：为正确的人提供正确的治疗（基于神经机制） （会持续烦躁的孩子），在合适的时间（学龄前，在烦躁问题恶化之前）。

PROJECT SUMMARY/ABSTRACT Irritability, defined as lowered threshold for anger when experiencing the RDoC construct frustrative non-reward, i.e., failing to receive expected rewards, is one of the most common reasons for pediatric psychiatric evaluation. Our work shows that early detection is critical: If irritability in preschool-age (3-6 years, before 1st grade) continues into school-age (after 1st grade), as it does for approximately 50% of preschool-age irritable children, such persistent irritability puts children on the path to mental disorder across the lifespan. Thus, identifying the neural mechanisms by which children persist vs. remit in irritability is paramount to intervene in the earliest phase of the clinical cascade. Irritability is linked with abnormalities in reward processing, which may lead to greater frustration when rewards are not received. Such reward processing vulnerabilities may be ameliorated by better inhibitory control, which normatively increases with maturation. However, the interplay between reward processing and inhibition in irritability trajectories is unknown. Investigating longitudinal changes in neural circuitry during this developmental period is important because the reward- and inhibition-related neural networks undergo substantial change and may be most malleable to early intervention. Our overall goal is to identify reward- and inhibition-related neural pathways that characterize persistence vs. remission of early childhood irritability. To this end, the proposed project will longitudinally characterize the neural and symptom trajectories of preschool-age children into school-age. We will collect measures of reward- and inhibitory control-related brain function at baseline and 24-month follow-up from 215 5-6-year-old children prior to 1st grade, alongside assessments of child irritability and inhibition at each 6-month follow-up. A comprehensive assessment of child (cognition, temperament, psychopathology), parent (psychopathology) and contextual factors (e.g., parenting, stressors) will also be assessed at baseline and 24-month assessments. Our central hypothesis is that young children with reward- and inhibition-related neural deficits are more likely to persist in irritability compared to those who remit. Specific aims are to identify (1) concurrent contributions of reward- and inhibition-related neural function to irritability at each age (preschool-age, school-age); (2) developmental changes in reward- and inhibition-related neural mechanisms of irritability trajectories from early to middle childhood; (3) early childhood reward- and inhibition-related neural predictors of irritability trajectories and future psychopathology; and (4) the moderating role of child sex, parent psychopathology, parenting, and life stress on these brain-behavior associations. This proposal will advance the field by revealing the neural circuitry of irritability risk and resilience. Innovative aspects include focusing on a key age range (5-6 years) to prevent later disorders, multiple time point imaging, and machine learning methodology. Our project is significant because it will pave the way for precision medicine for irritability: providing the right treatment (based on neural mechanisms) to the right people (children who will persist in irritability), at the right time (preschool age, before irritability problems worsen).