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).

项目摘要/摘要 易怒，定义为降低的愤怒阈值，因为造成RDOC构建令人沮丧的非回报， 即，未能获得预期的回报，是小儿精神病评估的最常见原因之一。 我们的工作表明，早期检测至关重要：如果学龄前年龄（3 - 6年，一年级之前3 - 6年）继续 进入学龄（一年级之后），就像大约50％的学龄前儿童易怒的儿童一样 持续的烦恼使儿童跨越整个生命的精神障碍。因此，识别神经 儿童坚持与责任感的机制对于在最早的阶段进行干预至关重要 临床级联。烦躁的性与奖励处理异常有关，这可能会导致更大 当未收到奖励时感到沮丧。这样的奖励处理漏洞可能会得到更好的改善 抑制性控制，法律上随着成熟而增加。但是，奖励之间的相互作用 易怒轨迹的处理和抑制是未知的。研究神经的纵向变化 在此发育期间的电路很重要，因为奖励和抑制相关的神经网络 经历重大变化，可能最能延展早期干预。我们的总体目标是确定 奖励和抑制相关的神经通路，这些神经途径是持久性与幼儿的缓解的特征 易怒。为此，拟议的项目将纵向表征神经和症状轨迹 学龄前儿童进入学龄。我们将收集与奖励和抑制控制有关的度量 在一年级之前的215个5-6岁儿童的基线和24个月的随访时，大脑功能 在每个6个月的随访中评估儿童易怒和抑制作用的评估。对儿童的全面评估 （认知，气质，心理病理学），父母（心理病理学）和背景因素（例如，育儿， 压力源）还将在基线和24个月的评估时进行评估。我们的中心假设是年轻 与奖励和抑制相关神经缺陷的儿童与 那些犯罪的人。具体目的是确定（1）与奖励和抑制相关神经的同时贡献 在每个年龄段的烦躁不良（学龄前，学龄）； （2）奖励和 从童年早期至中期的烦躁轨迹的抑制相关神经机制； （3）幼儿 奖励和抑制相关的易怒轨迹和未来心理病理学的神经预测因素； （4） 儿童性别，父母心理病理学，育儿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。 创新方面包括关注关键年龄范围（5-6岁），以防止以后的疾病，多次 点成像和机器学习方法。我们的项目很重要，因为它将为 精确医学以易怒：向合适的人提供正确的治疗（基于神经机制） （在适当的时间（学龄前，烦躁问题之前，会持烦躁不安的孩子）。