Neural mechanisms of risk for irritability across the transition to adolescence

青春期过渡期间烦躁风险的神经机制

• 批准号: 10549332
• 负责人: LEA R DOUGHERTY
• 金额: $ 37.59万
• 依托单位: SAN DIEGO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-03 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10549332
• 关键词: Adolescence; Adolescent; Adult; Age; Amygdaloid structure; Anger; Anxiety; Behavioral; Biological; Brain; Characteristics; Childhood; Clinical; Corpus striatum structure; Data; Data Set; Development; Diagnostic; Disease; Ethnic Origin; Formulation; Frustration; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Image; Intervention; Interview; Link; Longevity; Machine Learning; Measures; Mental Depression; Mental disorders; Modeling; Neural Inhibition; Neural Pathways; Neurophysiology - biologic function; Parents; Prefrontal Cortex; Psychopathology; Puberty; Race; Reporting; Research; Rewards; Risk; Role; Sampling; Signal Transduction; Subgroup; Suicide; Techniques; Time; Work; Youth; adverse outcome; brain based; brain behavior; catalyst; cognitive development; contextual factors; early adolescence; financial incentive; follow-up; functional outcomes; innovation; machine learning method; neural; neural circuit; neural correlate; neural network; neuromechanism; neuroregulation; novel; preadolescence; precision medicine; prevent; programs; prospective; recruit; response; reward processing; sex; socioeconomics; usability

PROJECT SUMMARY/ABSTRACT Irritability—exaggerated anger in response to non-reward—is among the most common psychiatric complaints. Because irritability in late childhood and adolescence predicts mental disorders across the lifespan, identifying the neural mechanisms involved in irritability across the transition to adolescence is paramount to intervene before youth irritability problems harden into entrenched psychiatric disorders in later adolescence and adulthood. 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 inhibitory control in irritability is unknown. Investigating longitudinal changes in neural circuitry is important because reward- and inhibition-related neural networks undergo substantial change from childhood through adolescence. Our overall goal is to identify reward- and inhibition-related neural pathways that characterize changes in irritability over the transition to adolescence. To this end, the proposal leverages data from the Adolescent Brain Cognitive Development (ABCD) Study, a large, national longitudinal sample of preadolescents assessed annually (N=~8,312 with usable datasets; baseline age=9-10; 1-Year Follow-Up [1-YRFU] age=10-11; 2-YRFU age=11-12). At baseline and 2-YRFU, youth complete monetary incentive delay and stop-signal tasks during fMRI acquisition that assess neural responses to reward and inhibitory control, respectively. Across all waves, youth irritability and co-occurring psychopathology are assessed using clinical interviews and parent- and youth-report measures, and multiple behavioral and parent- and youth-reported measures of youth reward processing and inhibitory control are collected. Our central hypothesis is that preadolescents with both reward- and inhibition-related neural deficits are more likely to show persistently high or increasing irritability across the transition to adolescence, whereas preadolescents with reward-related brain deficits, but better inhibition, will demonstrate decreases in irritability. Specific aims are to identify (1) separate and (2) interactive contributions of reward- and inhibition-related neural function to concurrent irritability; to identify (3a) preadolescent reward- and inhibition-related neural predictors and (3b) developmental changes in reward and inhibition neural mechanisms, of irritability trajectories and future psychopathology across the transition to adolescence; and to explore (4) the moderating role of developmental-biological-contextual factors (sex, puberty, race/ethnicity, SES, familial characteristics) on these brain-behavior relationships. This proposal will advance the field by revealing the neural circuitry of irritability. Innovative aspects include focusing on a key age range (transition to adolescence) to prevent adult disorders, multiple time point imaging, formulation of a novel and comprehensive reward-based model of irritability, machine learning methodology, and replication analyses. Our project is significant because it will be a catalyst for a research program to inform precision medicine for irritability.

项目概要/摘要 烦躁——对没有奖励而表现出的过度愤怒——是最常见的精神疾病之一。 因为童年晚期和青春期的烦躁预示着一生中的精神障碍，因此识别 涉及青春期过渡期间烦躁的神经机制对于干预至关重要 在青少年的烦躁问题在青春期后期恶化为根深蒂固的精神疾病之前 成年期的烦躁与奖励处理的异常有关，这可能会导致更大的挫败感。 当没有收到奖励时，这种奖励处理漏洞可以通过更好的抑制来改善。 然而，奖励处理和控制之间的相互作用通常会随着成熟而增加。 研究神经回路的纵向变化很重要。 因为奖励和抑制相关的神经网络从童年到 我们的总体目标是确定与奖励和抑制相关的神经通路。 为此，该提案利用了来自青春期过渡期间烦躁情绪的变化。 青少年大脑认知发展 (ABCD) 研究，一项针对青春期前儿童的大型全国纵向样本 每年评估（N=~8,312，具有可用数据集；基线年龄=9-10；1 年随访 [1-YRFU] 年龄=10-11； 2-YRFU 年龄=11-12)。在基线和 2-YRFU 下，青少年完成金钱激励延迟和停止信号任务。 在功能磁共振成像采集过程中，分别评估对奖励和抑制控制的神经反应。 通过临床访谈和家长评估来评估波动、青少年烦躁和同时发生的精神病理学。 和青年报告措施，以及多种行为和家长和青年报告的青年奖励措施 我们的中心假设是，青春期前的青少年同时具有奖赏- 与抑制相关的神经缺陷更有可能表现出持续较高或不断增加的烦躁情绪 过渡到青春期，而具有与奖赏相关的大脑缺陷但具有更好抑制能力的青春期前儿童，将 证明烦躁性降低。具体目标是确定 (1) 单独贡献和 (2) 交互贡献。 奖励和抑制相关的神经功能对并发烦躁的影响；以确定（3a）青春期前的奖励- 和抑制相关的神经预测因子以及（3b）奖赏和抑制神经的发育变化 向青春期过渡的烦躁轨迹和未来精神病理学的机制； 探索 (4) 发育生物背景因素（性别、青春期、种族/民族、社会经济地位、 该提案将通过揭示这些大脑行为关系来推动该领域的发展。 烦躁的神经回路的创新方面包括关注关键年龄范围（过渡到）。 青春期）预防成人疾病，多时间点成像，制定新颖且全面的 我们的项目是基于奖励的烦躁模型、机器学习方法和复制分析。 意义重大，因为它将成为一项研究计划的催化剂，为烦躁症的精准医学提供信息。