Binge eating disorder: from bench to bedside.

What makes us repeat behaviors compulsively that we ultimately regret? One intriguing behavior is that of binge eating—a pattern of food intake that is defined as recurring episodes of rapid, out-of-control overeating in which food is consumed in larger amounts than normal over a short period of time to the point of being uncomfortably full. Binge eating disorder (BED) has been accepted in The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and is the most common eating disorder, with a lifetime prevalence of 1.4% to 3%. BED occurs without compensatory purging and is strongly associated with obesity but also occurs without obesity. Differentiating BED from obesity without BED can deconstruct the complex heterogeneity of obesity and identify more specific treatment targets. Understanding the pathophysiology of BED allows us to delineate and optimize mechanisms of efficacy underlying psychotherapeutic and pharmacological interventions; identify novel drug targets, including neurotransmitter and peptidergic targets; and identify cognitive, physiological, and neural biomarkers as treatment targets. In this set of translational articles on BED, we review preclinical animal models and the influence of dopaminergic, opioidergic, and peptidergic systems, and also translational studies on human epidemiology, genetics, cognitive and neuroimaging correlates, and clinical treatment studies. Understanding how BED might also overlap with or differ from other eating disorders, impulsiveand compulsive-spectrum disorders, and substance and behavioral addictions is particularly relevant in light of the current trend toward dimensional psychiatry and understanding endophenotypes that may link seemingly diverse disorders. From a dimensional perspective, binge eating behavior overlaps across several eating disorders, including binge eating disorder, bulimia nervosa, and the binge-purge subtype of anorexia nervosa, along with subsyndromal expressions in the general population with and without obesity. Similarly from a dimensional perspective, binge eating can be conceptualized beyond the simple phenomenon of eating, to identifying genetic, molecular, cognitive, and neural endophenotypes that may link this behavior of persistent, out-of-control, rapid consumption of a highly palatable food (or natural reward) with other behaviors within the impulsivecompulsive spectrum disorders, or substance and behavioral addictions. The general concepts of “food addiction” and “eating addiction” have been raised by previous reviews and are not without controversy; however, BED appears to have greater support for a relationship with disorders of addiction, although is not specifically the subject of this current review. This set of articles is particularly timely, as lisdexamfetamine, a pro-drug of dextroamphetamine that blocks monoaminergic transporter reuptake of norepinephrine and dopamine, was approved by the United States Food and Drug Administration to treat BED in adults in January 2015. Together, preclinical reviews focus on binge eating rodent models, the role of dopamine and opioidergic mechanisms across rodent and human studies, and also an emerging literature on the influence of peptides. Avena and colleagues review the rodent model of sucrose binge eating: rodents exposed to food deprivation and access to sucrose solution show a rapid escalation of sucrose intake or bingeing, along with persistent dopamine release and delayed acetylcholine release in the nucleus accumbens, symptoms of withdrawal with food deprivation and cross-sensitization with amphetamine. The authors further discuss preclinical studies targeting orexin antagonism, modulation of dopamine receptors or suppression of dopamine synthesis, mu-opioid receptor antagonism, and GABAB agonism. Chiara and Pietro focus on dissecting the role of the opioidergic system in BED, particularly focusing on the mu-opioid receptor, and relevant neural and cognitive processes. The authors emphasize the relevance * Address for correspondence: Valerie Voon, University of Cambridge, Department of Psychiatry, Addenbrookes Hospital, Level, E4, Box 189, Hills Road, Cambridge CB2 0QQ, UK. (Email: [email protected]) CNS Spectrums (2015), 20, 520–521. © Cambridge University Press 2015 doi:10.1017/S109285291500067X