Nutritional deficiency and dopamine: A neurodevelopmental study of starvation effects in adolescent anorexia nervosa

神经性厌食症(AN)是一种严重的、可能危及生命的疾病，通常出现在 十几岁。虽然AN是一种具有无数症状的复杂疾病，但热量限制是核心 行为障碍，其特征是对饮食脂肪的特定限制。汇聚的数据表明 AN与多巴胺系统的紊乱有关。多巴胺系统发展相当快。 在青春期，充足的营养对大脑的健康发育起着重要作用。然而，饮食的影响 限制和相关的饥饿状态是AN的固有特征，人们对此知之甚少。个人 典型的饮食限制开始加速，卡路里的减少和体重的减轻 以及相关症状，包括焦虑和抑郁。这种级联模式最常见的是展开 在青春期，如果不是这样，可能会导致终生与饮食、身体形象和情绪障碍作斗争 坚持不懈。限制性饮食模式导致许多营养素的可获得性降低，其中一些 在青少年大脑发育过程中尤为重要。这里，我们重点介绍多不饱和脂肪(PUFA) 和酪氨酸，它们对多巴胺的功能和发育都是至关重要的 系统。 我们的建议旨在检验这一重要假设，即在出现饮食限制的青少年中 这是疾病固有的，在大脑的关键窗口期间对多巴胺(DA)系统产生负面影响 发展，具有持久的影响。我们预测，这些营养缺陷将与结构性 和DA系统的功能障碍(基线MRI扫描采用气管造影术、神经黑色素-MRI和 预测误差-fMRI)。我们预测，这些营养不足甚至会对DA系统产生持久的影响 当体重恢复成功时，1年后复查核磁共振。来评估存在的影响 体重不足，我们将包括患有非典型AN的患者，他们表现出所有AN的临床特征，但不是 体重不足，为期一年的纵向评估将衡量这些营养物质的持久影响 赤字。 这项拟议的研究具有直接的翻译治疗意义--例如增强电流 营养补充治疗(包括重新喂养)，从而保护发育中的大脑和 减少青少年AN的长期负面后遗症。以现有的知识，这样的试验将是 作为AN相关饥饿对大脑发育影响的特定营养物质，还为时过早 未知。我们的目标是通过研究多不饱和脂肪酸和酪氨酸是否介导DA的异常来弥合这一差距 患有AN和不典型AN的青少年的系统。

Anorexia nervosa (AN) is a severe and potentially life-threating condition that typically emerges in the teenage years. While AN is a complex disorder with myriad symptoms, caloric restriction is the central behavioral disturbance, and is characterized by a specific restriction of dietary fat. Converging data indicate that AN is associated with disturbances in the dopamine system. The dopamine system develops considerably during adolescence, and adequate nutrition plays a role in healthy brain development. Yet the effects of dietary restriction and the associated starved state that is an inherent feature of AN is poorly understood. Individuals with AN typically initiate dietary restrictions that accelerate, with mounting caloric reductions and weight loss and associated symptoms including anxiety and depression. This cascading pattern most commonly unfolds during adolescence and can lead to life-long struggles with eating, body image, and mood disturbance, if not unremitting AN. The restrictive eating pattern leads to decreased availability of many nutrients, some of which are particularly important in adolescent brain development. Here, we focus on polyunsaturated fats (PUFAs) and tyrosine which are specifically known to be critical for the functioning and development of the dopamine system. Our proposal aims to test the overarching hypothesis that among teens who develop AN, dietary restriction which is intrinsic to illness negatively impacts the dopamine (DA) system during a critical window of brain development, with enduring effects. We predict that these nutritional deficits will be associated with structural and functional disturbances in the DA system (baseline MRI scans with tractography, neuromelanin-MRI, and prediction error-fMRI). We predict that these nutritional deficits have enduring effects on the DA system even when weight restoration is successful, as evidenced by repeat MRI at 1 year. To assess the impact of being underweight, we will include individuals with atypical AN, who show all clinical features of AN but are not underweight, and 1-year longitudinal assessments will measure the enduring impact of these nutritional deficits. The proposed research has direct translational therapeutic implications – such as augmenting current treatments (including refeeding) with nutrient supplementation, thereby protecting the developing brain and curtailing the long-term negative sequelae of adolescent AN. With extant knowledge, such trials would be premature as the specific nutrients underlying AN-related starvation effects on brain development are unknown. We aim to close this gap by examining whether PUFAs and tyrosine mediate abnormalities in the DA system in adolescents with AN and atypical AN.