Appetite Hormones in Binge Eating Disorder

描述（由申请人提供）：本赠款提案是对NIH通知NOT-OD-09-058的回应，NIH宣布恢复法案资金可用于竞争修订。“目的是研究在正常条件下调节食物摄入的生物学机制，以及在暴食症（BED）中的压力源。我们计划招募24名有床位的肥胖受试者（S）（12个月，12岁）、24名没有床位的肥胖受试者（12个月，12岁）和24名没有床位的瘦S（12个月，12岁）。在最初的咨询中，S将接受招募筛选，并评估身高、体重、腰围和体脂。在第二天，他们将进行腹部MRI和体格检查。作为父母资助的一部分，在两个平衡测试日（一个在上午，一个在下午），他们将在测试餐之前和之后测量食欲相关激素，然后进行压力测试，并自由进食多项食物。竞争性修订部分将扩展对压力部分的食欲反应：在另外两个单独的测试日，fMRI将用于检查大脑激活区域对高适口性食物（HPF）的视觉刺激的反应，与低适口性食物（LPF）和非食物（NF）进行比较。在其中一天，功能性磁共振成像扫描之前将进行社会评估冷加压试验（SECPT），这是一种压力测试，参与者将一只手放在一盆冰水中，同时进行录像。另一天，扫描将遵循一个控制条件，其中参与者将一只手放在一盆温水中。SECPT和对照条件都将在受试者坐在扫描仪上时进行，就在扫描之前。与肥胖的非BED S相比，我们预计肥胖的BED S在与计划摄入相关的区域中显示出增加的激活（例如，腹侧运动前皮质）和食物奖励（例如，内侧眶额皮质[OFC]），并且，在应激条件下，与食物奖励和不良情绪调节相关的区域的激活增加（例如，腹侧杏仁核、前扣带回）。与瘦的nonBED S相比，我们预计肥胖的nonBED S在与食欲奖励相关的区域显示出增加的激活（例如，内侧和外侧OFC、海马、纹状体），以及与抑制食物摄入和饱腹感相关的区域中的脑激活降低（例如，背外侧前额叶皮层，后下丘脑[即，腹内侧核]）。这些组之间的差异，预计将存在以下控制条件，但更显着的压力。 公共卫生相关性：肥胖症的流行使得研究暴饮暴食症（BED）的病理生理学变得重要，BED发生在肥胖个体的重要子集中。BED可以说是最常见的饮食失调症，是许多超重个体痛苦的主要来源，并且可能与较差的预后和对治疗的抵抗有关。目前，BED的生物学基础和机制，包括神经基础和与无BED的肥胖的差异，知之甚少。我们计划使用脑成像技术来观察实验室压力刺激后，肥胖个体（有或没有BED）和瘦S型个体（没有BED）的大脑对视觉食物刺激的反应。这些发现可能会改善BED和肥胖的诊断和治疗。

DESCRIPTION (provided by applicant): This grant proposal is in response to NIH notice NOT-OD-09-058, 'NIH Announces the Availability of Recovery Acts Funds for Competing Revision.' The objective is to study the biological mechanisms regulating food intake under normal conditions and following a stressor in Binge Eating Disorder (BED). We plan to enroll 24 obese subjects (S's) with BED (12m, 12f), 24 obese S's without BED (12m, 12f) and 24 lean S's without BED (12m, 12f). At an initial consultation, S's will undergo recruitment screening and have height, weight, waist circumference, and body fat assessed. On a second day, they will have an abdominal MRI and a physical exam. As part of the parent grant, over two counterbalanced testing days (one in the morning and one in the afternoon), they will have appetite-related hormones measured before and after a test meal followed by a stress test, and multi-item ad libitum meal. The competitive revision component will expand on the appetite response to the stress component: On two additional separate days of testing, fMRI will be used to examine areas of brain activation in response to visual stimuli of high-palatability foods (HPF), compared with low-palatability foods (LPF), and non-foods (NF). On one of these days, the fMRI scan will be preceded by a Socially-Evaluated Cold Pressor Test (SECPT), a stress test in which the participant places one hand in a basin of ice water while being videotaped. On the other day, the scan will follow a control condition, in which the participant places a hand in a basin of warm water. The SECPT and control condition will both be conducted while the participant sits on the scanner table, just prior to scanning. Compared with obese nonBED S's, we expect the obese BED S's to show increased activation in areas associated with planned ingestion (e.g., ventral premotor cortex) and food reward (e.g., medial orbitofrontal cortex [OFC]), and, in the stress condition, increased activation in areas associated with food reward and poor emotional regulation (e.g., ventral amygdala, anterior cingulate). Compared with lean nonBED S's, we expect obese nonBED S's to show increased activation in areas associated with appetitive reward (e.g., medial and lateral OFC, insula, hippocampus, striatum), and decreased brain activation in areas associated with the inhibition of food intake and satiety (e.g., dorsolateral prefrontal cortex, posterior hypothalamus [i.e., ventromedial nucleus]). These differences among groups are expected to be present following the control condition but much more pronounced following the stressor. PUBLIC HEALTH RELEVANCE: The rising obesity epidemic makes it important to study the pathophysiology of Binge Eating Disorder (BED), which occurs in a significant subset of obese individuals. BED is arguably the most common eating disorder, a major source of distress for many overweight individuals, and may be associated with poorer prognosis and resistance to treatment. Currently, the biological substrates and mechanisms underlying BED, including the neural basis and the differences from obesity without BED, are poorly understood. We plan to use brain imaging to observe the brain's responses to visual food stimuli after a laboratory stressor in obese individuals with and without BED and in lean S's without BED. These findings may lead to improved diagnosis and treatment of BED and obesity.