Longitudinal Assessment of Neural Circuits in Adolescents with Anorexia Nervosa

原始项目摘要R 01 MH 110445 神经性厌食症（AN）是一种严重的精神疾病，死亡率最高的任何 精神障碍目前的治疗是不充分的，没有药理学试剂， 证明有效。更好地了解AN的发展和精神病理学是 非常需要。我们提出了一个纵向的，多模式的MRI研究奖励和习惯电路， 与年龄匹配的健康对照组（HC）相比， 两年我们专注于青春期，因为这是一个关键的，但研究不足，在AN时期。 病理性节食通常出现在青春期，AN的病程通常是 在此期间确定，大约一半的青少年显示完全恢复，而 其余的人忍受着长期的疾病。了解神经生物学机制， 一些青少年发展为持续性AN，而另一些则缓解，对于发展最有效的治疗至关重要。 干预措施。 我们的研究将研究指导食物选择和连接的神经机制， 患有AN的青少年中的中脑边缘系统和习惯相关回路， 与那些汇款，并与HC比较。我们将在基线检查这些神经回路 研究它们的发展轨迹。我们的食物选择任务捕捉限制性摄入， 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。在3个时间点使用纵向多模式MRI，我们将首先测试 中脑边缘奖励和背侧习惯回路的功能和连通性是否可以预测 长期的AN。其次，我们将研究这两个神经系统的纵向变化， 感兴趣的电路我们预测，在基线时，AN青年的限制性食物选择将是 介导的mesolimbic奖励电路;然而，在第2年的后续行动，在青少年为谁， 如果疾病持续存在，限制性食物选择将由背侧纹状体习惯回路介导。的 研究将（i）绘制青少年AN的奖励和习惯回路的发展轨迹; (ii)推进我们对AN持续慢性化的机制的理解，以及（iii） 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.