Brain and Adipose Contributors to Food Seeking in Youth with Adrenal Hyperplasia



 DESCRIPTION (provided by applicant): The goal of the proposed mentored research is to investigate the neurobiology of food-seeking behaviors in children, and to provide Dr. Mimi Kim the in-depth training and mentorship to become an independent investigator in childhood obesity and metabolism. This proposal targets children with congenital adrenal hyperplasia (CAH) as a natural human model for the study of brain and adipose contributors to obesity. Her long-term goal is to become a clinical research leader in childhood obesity with an emphasis on prevention and treatment. Dr. Kim joined the Department of Pediatrics at the Keck School of Medicine of USC and the Division of Endocrinology at Children's Hospital Los Angeles in 2009 under the mentorship of Dr. Mitchell Geffner, an expert in childhood endocrine disorders, including CAH. Children with CAH have abnormalities in neuroendocrine function and brain structures related to self-control and reward, and are more likely to be obese than children without CAH. Specifically, Dr. Kim will measure food-seeking behavior, body fat, metabolic hormones, and brain activity in regions involved in reward (e.g., amygdala and nucleus accumbens) and inhibitory control (pre-frontal cortex) in children with CAH and in an unaffected comparison group (Non-CAH). Prior research has shown that children with CAH have abnormal amygdala volumes and function, and decreased inhibitory control during motivated behavior. Food-seeking behaviors have not been studied in children with CAH; however, there is a wealth of animal research on impaired amygdala function and food- seeking behavior. Dr. Kim hypothesizes that 1) a small amygdala, as observed in CAH, is associated with obesity, and that 2) children with CAH exhibit less inhibitory control and greater brain reward response to highly palatable food cues. The specific aims are to: 1) determine whether amygdala size is inversely associated with adiposity and body composition in CAH youth vs. Non-CAH youth; 2) determine whether activation of inhibitory control regions is decreased and activation of reward regions is increased in response to food cues in CAH youth; and 3) evaluate decision-making with regard to food choices in CAH and Non-CAH groups from Aim 1. Through mentored training and didactic learning, Dr. Kim will develop specific expertise in: 1) structural magnetic resonance imaging (MRI) of the brain and abdomen, 2) functional MRI of the brain and administering a food cues-based task in the scanner, 3) a neurobehavioral task involving food decision- making, and 4) statistical methods useful for conducting human research. Guided by highly expert and collaborative mentors from multiple disciplines, Dr. Kim will acquire technical skills and an understanding of how to effectively conduct and lead team science. Her project will establish a human model for the study of the amygdala, appetite, food-seeking behaviors, and obesity in children using sophisticated MRI measures. Understanding the neurobiology of food-seeking behaviors in children could inform much-needed development of interventions for obese children with and without CAH.