Brain Reward Circuits and Computational Modeling in Adolescent Anorexia Nervosa

青少年神经性厌食症的大脑奖励回路和计算模型

基本信息

批准号：
8517204
负责人：
Guido KW Frank
金额：
$ 29.58万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-26 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8517204
关键词：
17 year old Accounting Adolescent Adult Affect Age American Psychiatric Association Animal Model Anorexia Nervosa Anxiety Basic Science Biological Markers Biology Body Image Body Weight decreased Brain Brain imaging Cause of Death Chronic Disease Cognition Computer Simulation Data Death Rate Disease Dopamine Eating Eating Disorders Education Emotions Failure Female Female Adolescents Food Food Processing Fright Functional Magnetic Resonance Imaging Goals Hormones Hydrocortisone Inorganic Sulfates Intervention Learning Link Magnetic Resonance Malnutrition Methods Modeling Motivation Neurotransmitter Receptor Neurotransmitters Outcome Pathologic Pathway interactions Patients Pharmaceutical Preparations Process Public Health Recovery Research Rewards Role Saliva Scanning Shapes Simulate Staging Steroids Stimulus Stress System Taste Perception Testing Time Underweight Unspecified or Sulfate Ion Sulfates Weight Weight Gain age group base conditioning critical period dehydroepiandrosterone expectation feeding food restriction improved insight mathematical model mortality neurosteroids novel response restoration reward circuitry reward processing

项目摘要

DESCRIPTION (provided by applicant): Anorexia nervosa (AN) is the third most common chronic illness among adolescents, and its mortality rate is 12 times higher than the death rate associated with all causes of death for females 15-24 years old. AN is characterized by severe weight loss and refusal to eat, suggesting altered brain processing of food rewards. In this application we will study in adolescents with AN brain reward pathways, and how those circuits are affected by malnutrition and re-feeding, as well as stress hormones that are frequently altered in AN. Our long term goal is to characterize pathologic brain circuits in AN that are biomarkers for the disorder, link those alterations to specific neurotransmitter mechanisms, and identify potential treatment targets for adolescent AN. In Aim 1. we test the hypothesis that adolescent AN is characterized by an increased response of dopamine related brain reward pathways. The proposed results will suggest that malnutrition in adolescent AN is associated with heightened brain reward sensitivity. In Aim 2. We test the hypothesis that weight recovered adolescent AN will have improved brain reward sensitivity compared to AN who did not restore weight, but will still show an exaggerated brain response compared to control adolescents. This will indicate long lasting alterations in brain reward function in adolescent AN beyond weight recovery. In Aim 3. We will test the hypothesis that the stress, feeding and reward related hormones cortisol, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), will be associated with increased reward sensitivity in adolescent AN. This will indicate potential mechanisms that contribute to altered reward processing in adolescent AN. We will study adolescents with restricting type AN, ages 12-17 years old, when underweight at the begin of treatment, as well as after either successful weight restoration or failure to restore weight. Results will be compared to age and education matched healthy adolescents. We will use taste and monetary reward stimuli and tasks that are related to brain dopamine function, together with functional magnetic resonance brain imaging (fMRI). We will examine adolescent AN brain response to reward stimulus expectation, as well as unexpected and expected receipt of reward stimuli. Those brain processes have important implications on reward learning and conditioning. We will further apply on the brain imaging results computational models that simulate brain dopamine action, and this will help getting insight into dopamine related brain function in adolescent AN. Those models will also help identify the larger brain reward circuitry that involves the effects of cognition and emotion on brain reward function in adolescent AN and healthy controls. The stress hormones cortisol, DHEA and DHEA-S have implications on feeding and brain dopamine function and show alterations in AN. We will analyze those neurosteroid hormones in saliva and test their affect on brain reward function in adolescent AN.

描述（由申请人提供）：神经性厌食症（AN）是青少年中第三大常见的慢性疾病，其死亡率比15-24岁的女性的所有死亡率相关的死亡率高12倍。 A的特征是严重减肥和拒绝吃，表明食物奖励的大脑加工改变了。在此应用中，我们将研究具有大脑奖励途径的青少年，以及这些电路如何受到营养不良和重新喂养的影响，以及经常在AN中改变的压力激素。我们的长期目标是表征是该疾病的生物标志物中的病理脑回路，将这些改变与特定神经递质机制联系起来，并确定青少年AN的潜在治疗靶标。在AIM 1中。我们检验了以下假设：青少年A的特征是多巴胺相关的大脑奖励途径的反应增加。提出的结果将表明青少年营养不良与大脑奖励灵敏度的提高有关。在AIM 2中。我们检验了以下假设：与没有恢复体重的人相比，体重恢复的青少年将提高大脑奖励敏感性，但与对照青少年相比，仍然会显示出夸张的大脑反应。这将表明青少年脑奖励功能的持久变化是超出体重恢复的。在AIM 3中。我们将检验以下假设：压力，喂养和奖励相关的激素皮质醇，脱氢表甲激素（DHEA）及其硫酸盐（DHEA-S）将与青少年奖励敏感性提高有关。这将表明潜在的机制有助于改变青少年的奖励处理。我们将研究限制AN型的青少年，年龄在12-17岁之间，当时在治疗开始时体重不足以及成功的体重恢复或无法恢复体重后。结果将与年龄和教育与健康的青少年相匹配。我们将使用与脑多巴胺功能相关的口味和金钱奖励刺激以及功能性磁共振脑成像（fMRI）。我们将研究青少年对奖励刺激期望的反应，以及意外的和预期的奖励刺激。这些大脑过程对奖励学习和条件具有重要意义。我们将进一步应用大脑成像结果计算模型，以模拟脑多巴胺作用，这将有助于深入了解青少年AN中与多巴胺相关的大脑功能。这些模型还将有助于确定涉及认知和情感对青少年和健康控制中大脑奖励功能的影响的更大的大脑奖励电路。压力激素皮质醇，DHEA和DHEA-S对喂养和脑多巴胺功能有影响，并显示AN中的改变。我们将分析唾液中的那些神经类固醇激素，并测试其对青少年AN中脑奖励功能的影响。