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.
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.
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