General Brain Arousal and Risk for Eating Disorder

一般大脑唤醒和饮食失调的风险

• 批准号: 10656518
• 负责人: THOMAS B HILDEBRANDT
• 金额: $ 40.12万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-22 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10656518
• 关键词: 10 year old; 12 year old; 13 year old; Acceleration; Accounting; Adolescence; Adolescent; Age; Anterior; Arousal; Back; Behavior; Behavioral; Binge Eating; Brain; Central Nervous System; Clinical; Cognitive; Computer Models; Corpus striatum structure; Cues; Data; Development; Diagnosis; Eating Behavior; Eating Disorders; Emotional; Endocrine; Ensure; Environment; Female; Food; Functional Magnetic Resonance Imaging; Genetic Risk; Gonadal Hormones; Graph; Hormonal; Hormones; Hyperphagia; Inferior; Insula of Reil; Link; Locomotion; Mediating; Mediation; Modality; Modeling; Motor Activity; Neurobiology; Neurosecretory Systems; Ovarian hormone; Positioning Attribute; Property; Psychological Techniques; Puberty; Research; Rewards; Risk; Role; Seminal; Sex Differences; Signal Transduction; Social Environment; Substance of Abuse; Testing; Twin Studies; Validation; Work; boys; cognitive development; cohort; cost; critical developmental period; disorder risk; early adolescence; emotional experience; feeding; financial incentive; follow-up; functional status; girls; heuristics; longitudinal dataset; model building; motivated behavior; preadolescence; prepuberty; psychosocial; response; reward processing; sensory input; sex; sexual dimorphism; social; theories

The prepubertal gonadal hormone surge that primes the rapid social and emotional development of adolescence has specific influences on female brains that may account for the accelerated risk for disordered eating and development of binge eating in girls relative to boys. We propose to test a model of sex differences in the risk for binge eating in early adolescence that emphasizes the differential influence of gonadal hormone status on the development of functional brain networks in girls relative to boys to account for the enhanced risk during this vulnerable period. The model leverages general brain arousal theory to predict the effect of gonadal hormones on functional brain networks, and builds on theoretical work by the MPI, seminal work by Dr. Kelly Klump and colleagues on moderated genetic risks for disordered eating in twin studies, and the pioneering work of Dr. Donald Pfaff and colleagues on the activating effects of gonadal hormones. The specific aims of this R01 project are two-fold: 1) to test for sex differences in the mediation of binge eating risk by gonadal hormonal influences on brain networks for arousal, reward processing, emotional salience, and inhibitory control at baseline and longitudinally over 2-year follow-up; and 2) to develop a computational model of general brain arousal to explain sex differences in the risk for binge eating in early adolescence. The central hypotheses are that (i) gonadal hormone status will predict the developmental status of functional brain networks for arousal, reward processing, emotional salience, and inhibitory control longitudinally in girls but not boys; (ii) these neuroendocrine interactions will mediate the risk for binge eating longitudinally in girls but not boys; and (iii) gonadal hormone status will predict covariation between these brain networks in girls but not boys, suggesting a sexually dimorphic mechanism for gonadal hormones to influence a range of behaviors characterized by altered responses to salient, rewarding, and stressful environmental cues. The large set of clinical, endocrine, and functional magnetic resonance imaging (fMRI) data collected for the Adolescent Brain Cognitive Development (ABCD) study at baseline and follow-up presents an ideal mechanism to test this model of sex differences in risk for binge eating during the critical developmental period in early puberty when gonadal hormone levels surge and maladaptive eating behaviors first emerge. These aims have direct

青春期前的性腺激素激增，引发了快速的社会和情感发展， 青春期对女性的大脑有特殊的影响，这可能是导致紊乱的风险增加的原因。 与男孩相比，女孩的饮食和暴饮暴食的发展。我们建议测试一个性别差异模型 在青少年早期暴饮暴食的风险中，强调了性腺激素的不同影响， 女孩大脑功能网络相对于男孩的发展状况，以解释风险增加的原因 在这个脆弱的时期。该模型利用一般的大脑唤醒理论来预测性腺激素的作用。 激素对大脑功能网络的影响，并建立在MPI的理论工作基础上， Klump及其同事在双胞胎研究中研究了饮食失调的遗传风险，以及开创性的研究 Donald Pfaff博士及其同事对性腺激素激活作用的研究。 这个R 01项目的具体目标有两个方面：1）测试性别差异的调解， 通过性腺激素对大脑网络的影响，兴奋，奖励处理，情绪 显著性和抑制控制在基线和纵向超过2年的随访;和2）制定一个 一般大脑唤醒的计算模型，以解释早期暴食风险的性别差异 青春期中心假设是：（i）性腺激素状态将预测发育 唤醒、奖励处理、情绪显著性和抑制控制的功能性脑网络的状态 纵向上，女孩而不是男孩;（ii）这些神经内分泌相互作用将介导暴饮暴食的风险 纵向女孩，但不是男孩;和（iii）性腺激素状态将预测这些大脑之间的协变 网络的女孩，但不是男孩，这表明性二态性机制的性腺激素的影响， 一系列行为，其特征是对突出的、奖励的和有压力的环境的反应改变。 线索收集的大量临床、内分泌和功能性磁共振成像（fMRI）数据， 青少年大脑认知发展（ABCD）研究在基线和随访时提出了一个理想的 机制来测试这个模型的性别差异的风险暴饮暴食在关键的发展时期 在青春期早期，性腺激素水平激增，不适应的饮食行为首次出现。 这些目标具有直接