Longitudinal Assessment of Neural Circuits in Adolescents with Anorexia Nervosa

神经性厌食症青少年神经回路的纵向评估

基本信息

批准号：
9917857
负责人：
Jonathan E Posner
金额：
$ 71.86万
依托单位：
NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-07 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9917857
关键词：
18 year old Adolescence Adolescent Adolescent and Young Adult Adult Aftercare Age Amygdaloid structure Anatomy Anorexia Nervosa Behavior Behavioral Body Weight decreased Brain Categories Characteristics Choice Behavior Chronic Corpus striatum structure Data Data Analyses Development Diagnostic Diet Diffusion Disease Disease remission Dorsal Eating Eating Behavior Food Functional Magnetic Resonance Imaging Functional disorder Habits Individual Intake Link MRI Scans Magnetic Resonance Imaging Measures Mediating Mental disorders Modeling Morbidity - disease rate Neurobiology Neurocognitive Outcome Pathologic Pharmacology Process Recovery Resistance Rest Rewards Severities Stereotyping Symptoms System Teenagers Testing Time Youth brain circuitry clinical predictors critical period design effective intervention experimental study follow-up habit learning interest longitudinal design mortality multimodality neural circuit neurobiological mechanism neuromechanism new therapeutic target novel prospective relating to nervous system reward circuitry reward processing severe mental illness tractography treatment effect treatment strategy

项目摘要

Project Summary Anorexia nervosa (AN) is a serious mental illness that confers the highest mortality rate of any psychiatric disorder. Current treatments are inadequate and no pharmacologic agents have proven effective. A better understanding of the development and pathophysiology of AN is greatly needed. We propose a longitudinal, multimodal MRI study of reward and habit circuits in youth (ages 14-18) with AN, compared with age-matched healthy controls (HC), followed over two years. We focus on adolescence because this is a critical, yet understudied, period in AN. Pathological dieting typically emerges during adolescence, and the course of AN is often determined during this period with approximately half of teens showing full recovery, whereas the rest endure persistent illness. Understanding the neurobiological mechanisms by which some teens develop persistent AN, while others remit, is critical to developing the most effective interventions. Our study will examine neural mechanisms guiding food choice and neural connectivity in mesolimbic and habit-related circuits among youth with AN who continue with illness compared with those who remit, and compared with HC. We will examine these neural circuits at baseline and study their developmental trajectories. Our Food Choice Task captures restrictive intake, a core behavioral disturbance in AN, and therefore we can directly examine the link between brain activity and eating behavior. Using longitudinal, multimodal MRI at 3- time points, we will first test whether the function and connectivity of mesolimbic reward and dorsal habit circuits predict the longer-term course of AN. Second, we will examine longitudinal changes within these two neural circuits of interest. We predict that at baseline, restrictive food choice in youth with AN will be mediated by mesolimbic reward circuitry; however, at year-2 follow-up, in teens for whom the disorder persists, restrictive food choice will be mediated by dorsal striatal habit circuitry. The study will (i) chart the developmental trajectories of reward and habit circuits in youth with AN; (ii) advance our understanding of the mechanisms by which AN persists to chronicity, and (iii) help develop targets for novel therapeutic strategies.

项目概要神经性厌食症（AN）是一种严重的精神疾病，死亡率是所有精神疾病中最高的紊乱。目前的治疗方法还不够充分，并且没有任何药物被证明是有效的。更好的非常需要了解 AN 的发展和病理生理学。我们建议纵向，与同龄人相比，患有 AN 的青少年（14-18 岁）奖励和习惯回路的多模态 MRI 研究健康对照（HC），随访两年多。我们关注青春期，因为这是一个关键的时期，但待研究，AN 时期。病理性节食通常出现在青春期，AN 的病程是通常在此期间确定大约一半的青少年表现出完全康复，而其余的忍受顽固的疾病。了解一些青少年发育的神经生物学机制持续性 AN（虽然其他情况会缓解）对于制定最有效的干预措施至关重要。我们的研究将检查指导食物选择的神经机制以及中脑边缘和大脑中的神经连接。与缓解后的患者相比，继续患病的 AN 青少年中的习惯相关回路，以及与HC相比。我们将在基线上检查这些神经回路并研究它们的发育轨迹。我们的食物选择任务捕获了限制性摄入，这是 AN 的核心行为障碍，因此我们可以直接检查大脑活动和饮食行为之间的联系。使用纵向、多模态 MRI 3- 时间点，我们首先测试中边缘奖赏和背侧习惯的功能和连通性是否电路预测 AN 的长期进程。其次，我们将研究这两者之间的纵向变化感兴趣的神经回路。我们预测，在基线时，患有 AN 的青少年的限制性食物选择将得到缓解通过中脑边缘奖励电路；然而，在第二年的随访中，对于疾病持续存在的青少年来说，限制性的食物选择将由背侧纹状体习惯回路介导。该研究将 (i) 绘制发育图 AN 青少年的奖励和习惯回路轨迹； (ii) 增进我们对机制的理解 AN 长期存在，并且 (iii) 帮助开发新的治疗策略的目标。