Longitudinal Assessment of Neural Circuits in Adolescents with Anorexia Nervosa

项目摘要 神经性厌食症是一种严重的精神疾病，在所有精神病患者中死亡率最高。 无序。目前的治疗方法是不充分的，没有任何药理药物被证明有效。更好的 对AN的发生和病理生理学的了解是非常必要的。我们提出了一个纵向的， 青年AN患者(14-18岁)奖赏和习惯回路的多模式MRI研究 健康对照组(HC)，随访两年以上。我们关注青春期，因为这是一个关键的，但 未成年学生，在一段时间内。病理性节食通常出现在青春期，病程是 通常是在这段时间内决定的，大约一半的青少年表现出完全康复，而其余的青少年 忍受着顽固的疾病。了解一些青少年发育的神经生物学机制 在其他人放松的同时，持续的干预对于制定最有效的干预措施至关重要。 我们的研究将检验指导食物选择和神经连接的神经机制 与缓解者相比，继续患病的青少年中与习惯相关的回路，以及 与HC相比。我们将在基线上检查这些神经回路，并研究它们的发展轨迹。 我们的食物选择任务捕捉到了限制性摄入量，这是一种核心的行为障碍，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、多模式磁共振成像在3- 时间点，我们将首先测试中脑边缘奖赏和背侧习惯的功能和连通性 电路预测了一种疾病的较长期进程。第二，我们将考察这两者之间的纵向变化。 感兴趣的神经回路。我们预测，在基线上，患有AN的青年的限制性食物选择将被中介 通过中边缘奖赏回路；然而，在第二年的随访中，在这种障碍持续存在的青少年中，限制性的 食物选择将通过背侧纹状体习性回路进行调节。这项研究将(I)绘制发展图 青少年AN奖赏和习惯回路的轨迹；(Ii)通过以下方式促进我们对机制的理解 它坚持慢性化，以及(Iii)帮助开发新的治疗策略的靶点。

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.