Longitudinal Assessment of Neural Circuits in Adolescents with Anorexia Nervosa

原始项目摘要R01 MH110445 神经性厌食症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。 精神障碍。目前的治疗方法是不充分的，没有药物可以 事实证明是有效的。更好地了解AS的发展和精神病理学 非常需要。我们提出了一个纵向的，多模式的MRI研究奖赏和习惯回路在 与年龄匹配的健康对照组(HC)相比，患有AN的青年(14-18岁)随访 两年了。我们关注青春期是因为这是一个关键但未被充分研究的时期。 病理性节食通常出现在青春期，而且病程通常是 在此期间确定的，大约一半的青少年表现出完全康复，而 其余的人忍受着顽固的疾病。了解神经生物学机制 一些青少年会发展成持续性AN，而另一些青少年则会发散，这对培养最有效的 干预措施。 我们的研究将检查指导食物选择和连接的神经机制 中脑边缘和习惯相关环路在继续患病的青年中的比较 与缓解者比较，并与HC进行比较。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获了限制摄入量，a 核心行为障碍，因此我们可以直接检查大脑之间的联系 活动和饮食行为。在3个时间点使用纵向、多模式磁共振成像，我们将首先测试 中脑边缘奖赏和背侧习性环路的功能和连通性是否可以预测 一个较长期的进程。第二，我们将检查这两个神经内的纵向变化 感兴趣的电路。我们预测，在基线情况下，患有老年痴呆症的年轻人的限制性食物选择将是 通过中脑边缘奖赏回路进行调节；然而，在第二年的随访中，对于那些 紊乱持续存在，限制性的食物选择将由背侧纹状体习性回路介导。这个 这项研究将(I)绘制青少年奖赏和习惯回路的发展轨迹； (2)增进我们对一个人坚持长期性的机制的理解；和(3) 帮助开发新的治疗策略的目标。

Original Project Summary R01 MH110445 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 psychopathology 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 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.