Longitudinal Assessment of Neural Circuits in Adolescents with Anorexia Nervosa

原始项目摘要 R01 MH110445 神经性厌食症（AN）是一种严重的精神疾病，死亡率最高。 精神障碍。目前的治疗方法还不够充分，也没有任何药物可以治疗 事实证明有效。更好地了解 AN 的发展和精神病理学 非常需要。我们提出了一项关于奖励和习惯回路的纵向、多模态 MRI 研究 与年龄匹配的健康对照 (HC) 相比，患有 AN 的青少年（14-18 岁）进行随访 两年。我们关注青春期，因为这是 AN 的一个关键但尚未得到充分研究的时期。 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已完全康复，而 其余的人则忍受着持续的疾病。了解神经生物学机制 一些青少年患有持续性 AN，而另一些青少年则有所缓解，这对于培养最有效的能力至关重要 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 与继续患病的 AN 青少年相比，中脑边缘和习惯相关回路 与那些汇款的人，并与 HC 进行比较。我们将在基线时检查这些神经回路 并研究他们的发展轨迹。我们的食物选择任务捕获了限制摄入量， AN 中的核心行为障碍，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态 MRI，我们将首先测试 中边缘奖赏和背侧习惯回路的功能和连接是否可以预测 AN 的长期病程。其次，我们将检查这两个神经元内的纵向变化 感兴趣的电路。我们预测，在基线时，患有 AN 的青少年的食物选择限制将是 由中脑边缘奖赏回路介导；然而，在第二年的随访中，在青少年中， 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 AN 青少年奖励和习惯回路的发展轨迹； (ii) 增进我们对 AN 持续存在的机制的理解，以及 (iii) 帮助制定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.