Longitudinal Assessment of Neural Circuits in Adolescents with Anorexia Nervosa

项目摘要 神经性厌食症（AN）是一种严重的精神疾病，其死亡率是所有精神疾病中最高的 disorder.目前的治疗是不够的，没有药理学药物已被证明是有效的。更好的 非常需要了解AN的发展和病理生理学。我们提出一个纵向的， 青少年（14-18岁）AN的奖励和习惯回路的多模式MRI研究，与年龄匹配的 健康对照组（HC），随访2年以上。我们关注青春期，因为这是一个关键的， 在AN的时候，病理性节食通常出现在青春期，AN的病程是 通常在这一时期确定，大约一半的青少年显示完全康复，而其余的青少年 忍受持续的疾病。了解一些青少年发展的神经生物学机制 持续性AN，而其他人则缓解，对于制定最有效的干预措施至关重要。 我们的研究将探讨指导食物选择的神经机制和中脑边缘系统的神经连接， 与缓解者相比，继续患病的AN青年与习惯相关的回路，以及 与HC相比。我们将在基线检查这些神经回路，并研究它们的发展轨迹。 我们的食物选择任务捕获限制性摄入，这是AN的核心行为障碍，因此我们可以 直接研究大脑活动和饮食行为之间的联系。使用纵向多模式MRI，在3- 时间点，我们将首先测试是否功能和连接的中脑边缘奖励和背习惯， 电路预测AN的长期过程。其次，我们将研究这两个领域的纵向变化， 感兴趣的神经回路我们预测，在基线，限制性食物选择的青年与AN将介导 然而，在第2年的随访中，对于那些障碍持续存在的青少年， 食物选择将由背侧纹状体习惯回路介导。本研究将（i）绘制发展 AN青少年的奖励和习惯回路轨迹;（ii）通过以下方式加深我们对机制的理解 其中AN持续到慢性，和（iii）帮助开发新的治疗策略的目标。

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.