Neural mechanisms of risk and resilience in early childhood irritability

儿童早期烦躁的风险和恢复力的神经机制

• 批准号: 10663081
• 负责人: LEA R DOUGHERTY
• 金额: $ 67.95万
• 依托单位: SAN DIEGO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10663081
• 关键词: 5 year old; 6 year old; Accounting; Adult; Age; Amygdaloid structure; Anger; Anxiety; Brain; Child; Child Rearing; Childhood; Chronic; Clinical; Cognition; Corpus striatum structure; Data; Development; Disease; Disease remission; Early Diagnosis; Early Intervention; Early identification; Evaluation; Feedback; Friends; Frustration; Functional Magnetic Resonance Imaging; Future; Goals; Image; Impairment; Internet; Interview; Life Stress; Link; Longevity; Machine Learning; Maintenance; Measures; Mental Depression; Mental disorders; Methods; Neural Inhibition; Neural Pathways; Neurophysiology - biologic function; Nursery Schools; Parents; Participant; Pattern; Persons; Phase; Prefrontal Cortex; Preventive; Psychopathology; Reporting; Research Domain Criteria; Rewards; Risk; Risk Factors; Role; School-Age Population; Services; Sex Ratio; Symptoms; Temperament; Time; Variant; Work; age related; brain behavior; contextual factors; early childhood; economic outcome; experience; financial incentive; first grade; follow-up; functional outcomes; innovation; machine learning method; middle childhood; neural; neural circuit; neural network; neuroimaging; neuromechanism; novel; precision medicine; prevent; recruit; resilience; reward processing; sex; socioeconomics; stressor; suicidal; support network

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).

项目概要/摘要 烦躁，定义为当经历 RDoC 构建的令人沮丧的无奖励时，愤怒的阈值降低， 即未能获得预期的奖励是儿科精神病学评估的最常见原因之一。 我们的研究表明，早期发现至关重要：如果学龄前儿童（3-6 岁，一年级之前）的烦躁情绪持续存在 进入学龄期（一年级后），大约 50% 的学龄前易怒儿童，例如 持续的烦躁会让孩子一生都走上精神障碍的道路。因此，识别神经 儿童持续烦躁或缓解烦躁的机制对于在烦躁的最早阶段进行干预至关重要 临床级联。烦躁与奖​​励处理异常有关，这可能会导致更大的 没有收到奖励时的挫败感。这种奖励处理漏洞可以通过更好的方法来改善 抑制控制，通常随着成熟而增加。然而，奖励之间的相互作用 烦躁轨迹的处理和抑制尚不清楚。研究神经的纵向变化 这个发育时期的电路很重要，因为与奖励和抑制相关的神经网络 经历重大变化，并且可能最容易进行早期干预。我们的总体目标是确定 表征幼儿期持续与缓解的奖励和抑制相关神经通路 易怒。为此，拟议项目将纵向描述神经和症状轨迹 学龄前儿童进入学龄期。我们将收集奖励和抑制控制相关的措施 研究人员对 215 名一年级前 5-6 岁儿童的基线脑功能和 24 个月的随访进行了研究 每 6 个月的随访评估儿童的烦躁性和抑制性。对孩子的全面评估 （认知、气质、精神病理学）、父母（精神病理学）和背景因素（例如，养育子女、 压力源）也将在基线和 24 个月评估时进行评估。我们的中心假设是年轻人 与奖励和抑制相关的神经缺陷的儿童相比，更有可能持续烦躁 那些汇款的人。具体目标是确定（1）奖励和抑制相关神经的同时贡献 对每个年龄段（学龄前、学龄）的烦躁起作用； (2) 奖励和奖励的发展变化 童年早期至中期烦躁轨迹的抑制相关神经机制； (3)幼儿期 与奖励和抑制相关的烦躁轨迹和未来精神病理学的神经预测因子；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大脑行为的调节作用 协会。该提案将通过揭示烦躁风险和恢复力的神经回路来推动该领域的发展。 创新方面包括关注关键年龄范围（5-6 岁）以预防以后的疾病、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 针对烦躁的精准医学：为正确的人提供正确的治疗（基于神经机制） （持续烦躁的孩子），在正确的时间（学龄前，烦躁问题恶化之前）。