General Brain Arousal and Risk for Eating Disorder

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The prepubertal gonadal hormone surge that primes the rapid social and emotional development of adolescence has specific influences on female brains that may account for the accelerated risk for disordered eating and development of binge eating in girls relative to boys. We propose to test a model of sex differences in the risk for binge eating in early adolescence that emphasizes the differential influence of gonadal hormone status on the development of functional brain networks in girls relative to boys to account for the enhanced risk during this vulnerable period. The model leverages general brain arousal theory to predict the effect of gonadal hormones on functional brain networks, and builds on theoretical work by the MPI, seminal work by Dr. Kelly Klump and colleagues on moderated genetic risks for disordered eating in twin studies, and the pioneering work of Dr. Donald Pfaff and colleagues on the activating effects of gonadal hormones. The specific aims of this R01 project are two-fold: 1) to test for sex differences in the mediation of binge eating risk by gonadal hormonal influences on brain networks for arousal, reward processing, emotional salience, and inhibitory control at baseline and longitudinally over 2-year follow-up; and 2) to develop a computational model of general brain arousal to explain sex differences in the risk for binge eating in early adolescence. The central hypotheses are that (i) gonadal hormone status will predict the developmental status of functional brain networks for arousal, reward processing, emotional salience, and inhibitory control longitudinally in girls but not boys; (ii) these neuroendocrine interactions will mediate the risk for binge eating longitudinally in girls but not boys; and (iii) gonadal hormone status will predict covariation between these brain networks in girls but not boys, suggesting a sexually dimorphic mechanism for gonadal hormones to influence a range of behaviors characterized by altered responses to salient, rewarding, and stressful environmental cues. The large set of clinical, endocrine, and functional magnetic resonance imaging (fMRI) data collected for the Adolescent Brain Cognitive Development (ABCD) study at baseline and follow-up presents an ideal mechanism to test this model of sex differences in risk for binge eating during the critical developmental period in early puberty when gonadal hormone levels surge and maladaptive eating behaviors first emerge. These aims have direct