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

营养缺乏和多巴胺：饥饿对青少年神经性厌食症影响的神经发育研究

• 批准号: 10534437
• 负责人: Jonathan E Posner
• 金额: $ 76.78万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-19 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10534437
• 关键词: Adolescence; Adolescent; Affect; Amino Acids; Anorexia Nervosa; Anxiety; Behavioral; Biological Factors; Body Image; Body Weight decreased; Brain; Caloric Restriction; Calories; Chronic; Clinical; Complex; Consumption; Corpus striatum structure; Data; Development; Dietary Fats; Dietary Practices; Diffusion; Disease; Disease remission; Dopamine; Eating; Food; Functional Magnetic Resonance Imaging; Individual; Intake; Knowledge; Lead; Learning; Life; Lipids; MRI Scans; Magnetic Resonance Imaging; Malnutrition; Measures; Mediating; Mental Depression; Mental Health; Mental disorders; Midbrain structure; Mood Disorders; Moods; Morbidity - disease rate; Nucleus Accumbens; Nutrient; Nutritional; Outcome; Patients; Pattern; Plasma; Play; Polyunsaturated Fatty Acids; Psychological reinforcement; Psychopathology; Records; Relapse; Research; Role; Severity of illness; Signal Transduction; Starvation; Supplementation; Symptoms; Teenagers; Testing; Translating; Tyrosine; Underweight; Youth; adolescent brain development; adolescent patient; affective disturbance; anxiety symptoms; associated symptom; brain tract; dietary restriction; dietary supplements; dopamine system; food restriction; functional MRI scan; imaging modality; mood symptom; mortality; neuromelanin; nutrition; peer; polyunsaturated fat; pre-clinical; premature; restrictive eating; severe mental illness; tractography; translational therapeutics; weight restoration; white matter

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.

神经性厌食症（AN）是一种严重的和潜在的危及生命的条件，通常出现在 十几岁的时候虽然AN是一种复杂的疾病，有无数的症状，但热量限制是核心。 行为障碍，其特征在于对膳食脂肪的特定限制。数据显示 AN与多巴胺系统紊乱有关多巴胺系统会显著发展 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 限制和作为AN的固有特征的相关饥饿状态知之甚少。个人 AN患者通常会开始饮食限制，这会加速热量减少和体重减轻 以及相关症状包括焦虑和抑郁。这种级联模式最常见的是 在青春期，如果没有，可能导致终身与饮食，身体形象和情绪障碍作斗争， 坚持不懈的限制性的饮食模式导致许多营养素的可用性下降，其中一些营养素 对青少年大脑发育尤为重要。在这里，我们专注于多不饱和脂肪（PUFA） 和酪氨酸，它们对多巴胺的功能和发育至关重要 系统 我们的建议旨在测试总体假设，即在患有AN的青少年中，饮食限制 这是疾病固有的负面影响多巴胺（DA）系统在一个关键的窗口， 发展，具有持久的影响。我们预测，这些营养不足将与结构性 和DA系统的功能障碍（基线MRI扫描与纤维束成像，神经黑色素MRI， 预测误差-fMRI）。我们预测，这些营养缺乏对DA系统有持久的影响， 当体重恢复成功时，通过1年时的重复MRI证明。为了评估 体重过轻，我们将纳入非典型AN患者，他们表现出AN的所有临床特征，但没有 一年的纵向评估将衡量这些营养措施的持久影响。 赤字 拟议的研究具有直接的转化治疗意义-例如增加电流 营养补充治疗（包括再喂养），从而保护发育中的大脑， 减少青少年AN的长期负面后遗症。根据现有的知识，这样的审判将是 早产，因为与AN相关的饥饿对大脑发育的影响相关的特定营养素， 未知我们的目标是通过检测PUFAs和酪氨酸是否介导DA的异常来缩小这一差距。 系统与AN和非典型AN的青少年。