Neurobiological Underpinnings of Obesity and Addiction: A Focus on Binge Eating Disorder and Implications for TreatmentPublished on Psychiatric Times(http://www.psychiatrictimes.com)

Neurobiological Underpinnings of Obesity and Addiction: AFocus on Binge Eating Disorder and Implications for TreatmentJuly 20, 2015 | CME [1]By Iris M. Balodis, PhD [2], Carlos M. Grilo, PhD [3], and Marc N. Potenza, PhD, MD [4]

This CME is intended to help differentiate binge eating disorder (BED) from other eating disordersand understand the mechanisms that may put BED into the realm of addiction disorders.

Premiere Date: July 20, 2015Expiration Date: January 20, 2017

This activity offers CE credits for:1. Physicians (CME)2. OtherACTIVITY GOALTo differentiate binge eating disorder (BED) from other eating disorders and understand themechanisms that may put BED into the realm of addiction disorders.LEARNING OBJECTIVESAt the end of this CE activity, participants should be able to:1. Recognize the differences between BED and other eating disorders2. Understand how BED relates to addiciton disorders3. Recognize treatment approaches—pharmacological and psychotherapeuticTARGET AUDIENCEThis continuing medical education activity is intended for psychiatrists, psychologists, primary carephysicians, physician assistants, nurse practitioners, and other health care professionals who seek toimprove their care for patients with mental health disorders.CREDIT INFORMATIONCME Credit (Physicians): This activity has been planned and implemented in accordance with theEssential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME)through the joint providership of CME Outfitters, LLC, and Psychiatric Times. CME Outfitters, LLC, isaccredited by the ACCME to provide continuing medical education for physicians.CME Outfitters designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credit™.Physicians should claim only the credit commensurate with the extent of their participation in theactivity.Note to Nurse Practitioners and Physician Assistants: AANPCP and AAPA accept certificates ofparticipation for educational activities certified for 1.5 AMA PRA Category 1 Credit™.DISCLOSURE DECLARATIONIt is the policy of CME Outfitters, LLC, to ensure independence, balance, objectivity, and scientificrigor and integrity in all of their CME/CE activities. Faculty must disclose to the participants anyrelationships with commercial companies whose products or devices may be mentioned in facultypresentations, or with the commercial supporter of this CME/CE activity. CME Outfitters, LLC, hasevaluated, identified, and attempted to resolve any potential conflicts of interest through a rigorouscontent validation procedure, use of evidence-based data/research, and a multidisciplinarypeer-review process.The following information is for participant information only. It is not assumed that theserelationships will have a negative impact on the presentations.Iris M. Balodis, PhD, has no disclosures to report.Carlos M. Grilo, PhD, reports that he has received grants and research support from the NationalInstitutes of Health, he is on the speakers bureau of Shire, and he is a consultant for Shire andSunovion.Marc N. Potenza, PhD, MD, reports that he is a consultant for Shire, INSYS, and RiverMend Health.Ashley Gearhardt, PhD (peer/content reviewer), has no disclosures to report.Applicable Psychiatric Times staff and CME Outfitters staff have no disclosures to report.UNLABELED USE DISCLOSURE

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Neurobiological Underpinnings of Obesity and Addiction: A Focus on Binge Eating Disorder and Implications for TreatmentPublished on Psychiatric Times(http://www.psychiatrictimes.com)

Faculty of this CME/CE activity may include discussion of products or devices that are not currentlylabeled for use by the FDA. The faculty have been informed of their responsibility to disclose to theaudience if they will be discussing off-label or investigational uses (any uses not approved by theFDA) of products or devices. CME Outfitters, LLC, and the faculty do not endorse the use of anyproduct outside of the FDA-labeled indications. Medical professionals should not utilize theprocedures, products, or diagnosis techniques discussed during this activity without evaluation oftheir patient for contraindications or dangers of use.Questions about this activity? Call us at 877.CME.PROS (877.263.7767)Obesity has been considered within an addiction framework with the term “food addiction” debatedas a potential clinical entity. Certain core addiction characteristics, such as diminished control or lossof control while eating, food cravings, and continued behaviors despite negative consequences,appear pertinent to some patterns of disordered eating. Systematic investigations intoneurobiological mechanisms underlying these features are ongoing in an effort to understandpotential contributions to different patterns of overeating. It is likely that obesity is the result ofmultiple factors. Genetics, environment, various overeating behaviors (from excess snacking toovereating of nutrition-poor but calorie-dense foods to binge eating), insufficient lifestyle physicalactivity, and various metabolic conditions may all contribute in complex ways to obesity.A central research goal is to define how different etiologies and pathways contribute to the manymanifestations of overeating and obesity. Discussing obesity as a unitary disorder may obfuscateresearch findings that pertain to this complex problem; therefore, our focus is on binge eatingdisorder (BED).The notion of food addiction has recently been applied to BED, which is defined by recurrentepisodes of consuming unusually large amounts of food. It is important to note that persons withBED experience a subjective sense of loss of control during these episodes, but they do not performthe extreme weight compensatory behaviors that characterize bulimia nervosa. BED is the mostprevalent eating disorder; it affects approximately 4% of the US population, occurs across all weightcategories, and is strongly associated with severe obesity.1,2 It is linked with increased risk ofpsychiatric and medical comorbidities. Moreover, BED exhibits behavioral and psychologicaldimensions that are distinct from other eating disorders.Although BED is currently categorized as an eating disorder in DSM-5, distinct parallels are noted inphenomenological/behavioral features between BED and addiction. Recurrent binging episodes, alack of control, and personal distress/negative social consequences appear as core characteristicsacross both disorders. Understanding the neural systems underlying these features is particularlyimportant because they contribute significantly to appetite regulation, weight, and treatmentresponse.Despite the prevalence and clinical impact of BED, functional and structural neuroanatomical studiesspecifically examining BED are only beginning to emerge. These neuroimaging studies arefundamental for demonstrating structural and functional brain characteristics supporting BED as acondition distinct from other forms of obesity or other forms of disordered eating (eg, anorexianervosa, bulimia nervosa). In addition, these studies clarify the clinical relevance of specific features.Reward processing in BEDGiven the frequent consumption of highly palatable foods during binge eating episodes, rewardprocessing needs to be considered in BED. Several neuroimaging studies in BED demonstrateincreased activity in prefrontal areas while viewing food stimuli.3-5 Specifically, food cues producegreater activity increases in the ventromedial prefrontal cortex/orbitofrontal cortex in individualswith BED than in healthy, overweight, or bulimic cohorts. This region not only processes multimodalinformation and encompasses the secondary taste cortex, but it also signals the motivationalproperties of food and other reinforcers, including drugs.6 Greater activity in the orbitofrontal cortexduring food cue exposure relates to higher reward sensitivity, which supports the idea thatindividuals with BED are hypersensitive to the motivational and rewarding properties of food.5Structural differences are also observed in persons with BED: gray matter volume differences havebeen identified in the medial prefrontal regions in these individuals; this is similar to gray mattervolume differences detected in substance-dependent populations.7-9

Palatable flavors (as compared with water) also stimulate greater responses in reward neurocircuitry,including the orbitofrontal cortex, insula, and striatum, in compulsive overeaters.10 Specifically,high-calorie foods (eg, chocolate milk) produce stronger connectivity between the ventral striatumand other reward regions, relative to water. Higher binge eating scores relate to stronger ventralstriatal connections and provide mechanistic information on how BED features might relate to

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Neurobiological Underpinnings of Obesity and Addiction: A Focus on Binge Eating Disorder and Implications for TreatmentPublished on Psychiatric Times(http://www.psychiatrictimes.com)

reward-related learning mechanisms.A reward system that is hyperresponsive to food/taste cues is consistent with theincentive-sensitization hypothesis in addiction that posits that addiction-related cues stimulate andeventually hijack reward neurocircuitry. A large body of research demonstrates that the striatum(particularly the ventral component including the nucleus accumbens) signals rewardanticipation.11-13 In persons with addictions, the striatum is involved with craving.14,15 Understandingwhether similar parallels in craving occur in BED and how these may be altered across the course ofthe disorder is important for future directions.Understanding responsiveness to non-food reward is also important because generalized rewardprocessing disturbances may play a role in the etiology and maintenance of BED. In contrast to foodcues, non-food reward cues (eg, monetary) produce relatively reduced frontostriatal responses inpersons who have BED relative to those who do not have BED. Differences in insula activity are alsoseen in persons with BED. Given the importance of this area in interoceptive processing andhomeostatic signaling, individuals who have BED may have difficulties integrating rewardinformation with their bodily state. In persons with BED, anticipation of monetary reward alsogenerates a diminished response in the ventral striatum, relative to non-BED obese individuals.16

This finding is particularly noteworthy because it parallels reduced anticipatory striatal processingreported in pathological gambling and alcohol-dependent populations, thereby supporting the idea ofsimilar neural alterations underlying reward processing across the disorders.17,18

Longitudinal studies will help clarify whether reduced anticipatory processing represents a precursorfor BED development. Nonetheless, these neuroimaging findings are consistent with the idea of areward deficiency syndrome in persons with BED similar to that proposed in individuals with drugaddictions. These findings suggest that blunted reward responsivity may promote the stimulation ofthe system through behaviors such as drug use, or in the case of BED, eating. In addition, thesestudies highlight important differences between obese subgroups. Obese individuals with BED andnon-BED obese individuals demonstrate significantly different neural responses; therefore, collapsingacross obesity subtypes risks obscuring important differences.Another recent neuroimaging study used brain activation patterns to discriminate various disorderedeating groups.19 Persons with BED had differential activation of insular, striatal, anterior cingulatecortex, and orbitofrontal cortex regions compared with obese non-BED persons, lean controls, andbulimic patients. In this way, increasing evidence supports distinct neurofunctional patterns thatdiscriminate between diagnostic conditions and clinical features.Cognitive control in BEDA reduced ability or willingness to control the amount of consumption and the frequency ofsubstance intake is a cardinal feature of both addiction and BED. Substance-dependent populationsdemonstrate reduced recruitment of prefrontal areas during cognitive-control tasks.20,21 However,few studies have examined the neurobiological underpinnings of cognitive-control characteristics inBED.One pilot study of generalized inhibitory processing found diminished activity in frontal areas, suchas the orbitofrontal cortex and the inferior frontal gyrus—which subserve self-regulation andinhibitory control—in persons with BED relative to non-BED obese and lean cohorts.22 Groupdifferences observed here appear driven by the BED group, supporting the idea for distinctcognitive-control differences in BED compared with other forms of obesity. The levels of eatingrestraint reported in the BED group were related to diminished orbitofrontal cortex and inferiorfrontal gyrus activity; in contrast, the non-BED obese and lean cohorts demonstrated positiverelationships between eating restraint and recruitment of these brain areas. These resultsdemonstrate that within the BED group, there is reduced recruitment of brain areas important forinhibitory control.Further research is necessary, but these findings nonetheless demonstrate parallel findings with bothsubstance-based and non–substance-based addictive disorders (eg, gambling). And, they support theidea that the ventromedial prefrontal cortex/orbitofrontal cortex areas may contribute toinhibitory-control problems across BED and addictions.BED treatments and early neuroimaging findingsEmerging evidence suggests that effective addiction treatments might have relevance and may alsoprove therapeutic for BED. Naltrexone, an opioid antagonist, has been found to reduce cravings andprevent relapse in alcohol dependence.23 There is some evidence that naloxone, an opioidantagonist, curtails the duration and magnitude of binge eating episodes.24 In lean and obese bingeeaters, the drug suppresses consumption of high-fat and sugary foods. Similarly, another opioidantagonist—GSK1521498—selectively reduces attentional bias for food cues as well as hedonic

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Neurobiological Underpinnings of Obesity and Addiction: A Focus on Binge Eating Disorder and Implications for TreatmentPublished on Psychiatric Times(http://www.psychiatrictimes.com)

preference and consumption of high-fat and sugary foods.25,26

In one of the first pharmacological imaging studies, Cambridge and colleagues27 examined theeffects of an opioid antagonist on food-cue response in obese individuals with moderate binge eatingsymptoms and found reduced striatal (pallidum/putamen) response to highly palatable food-cueimages. This study highlights this area as a hedonic hot spot whereby the opioid antagonist disruptsmotivational response to food while leaving the hedonic (subjective ratings) unaffected.These converging lines of evidence suggest the potential utility of testing naltrexone and otheropioid antagonists as BED treatment. It must be noted, however, that one randomized clinical trialfailed to show that naltrexone had a specific effect relative to placebo for improving eating disorderpathology in women with alcohol dependence.28 Collectively, however, these early studies suggestthat distinct neural systems may underlie motivational versus consumptive aspects of food, and thismay prove important for developing treatments targeting core BED characteristics.Striatal and prefrontal areas emerging as distinguishing BED characteristics also suggest potentialdopaminergic mechanisms, since these brain areas represent projection sites of thisneurotransmitter. Indeed, dopamine transmission alterations in this reward neurocircuitry areimplicated in the transition from substance use to addiction and potentially the shift from overeatingto bingeing in BED. A positron emission tomography (PET) study that compared obese individualswith and without BED during food-cue presentations found increased striatal dopamine releasefollowing a methylphenidate challenge in the BED group.29 Interestingly, a higher binge eating score,but not BMI, was related to greater extracellular dopamine release in the caudate during the foodstimulation task. This suggests a role for dopamine transmission in binge eating symptomatologyrather than weight per se. Thus, striatal dopamine neurotransmission appears important inmotivated food behavior, with altered signaling during incentive processing potentially contributingto BED symptomatology.Controlled treatment studies have found that several pharmacotherapies appear to be effective inBED for reducing binge eating over the short term.30,31 However, the longer-term effects ofmedications for BED are largely unknown or have not yet been shown.Of the various medications tested for BED, some have not been effective and most have notproduced significant weight losses (obesity is not a required feature of the BED diagnosis but is oftena comorbid physical problem and weight loss is often considered as a secondary outcome). Twonotable exceptions, topiramate and lisdexamfetamine, showed significant and substantial reductionsin both binge eating and weight.32,33 This year, the FDA approved lisdexamfetamine, adopamine-norepinephrine reuptake inhibitor originally used in the treatment of ADHD, for BED; thisis the only FDA-approved medication for BED (fluoxetine is FDA-approved for bulimia nervosa).However, the efficacy and safety of lisdexamfetamine for obesity have not been established, and theproduct labeling states that lisdexamfetamine is not indicated for weight loss.Specific psychotherapies for BED have been shown to have durable effects for up to severalyears.34,35 Cognitive-behavioral therapy is the best established treatment for BED. Strong supportalso exists for interpersonal psychotherapy and certain forms of behavioral weight lossinterventions.35,36 However, minimal weight losses have been reported despite robust improvementsin core binge eating psychopathology. Combining medication and psychological approaches hasgenerally not enhanced treatment outcomes. Collectively, although treatment research hasidentified effective approaches, improved interventions are needed because a sizeable minority ofpatients do not benefit sufficiently, and most patients fail to lose clinically meaningful weight.Few studies to date have applied neuroimaging to BED treatment; however, these already providesome information on potential treatment targets and mechanisms of treatments. For example, arecent pilot study showed how reward neurocircuitry recruitment relates to treatment outcomes:diminished activity in ventral striatal areas at the beginning of treatment related to persistentbingeing at the end of treatment.37 Individuals with BED who reported bingeing at the end of atreatment trial demonstrated significantly less activation within reward neurocircuitry (including theinferior frontal gyrus) to non-food reward cues at treatment onset. A study by McCaffery andcolleagues38 also found a link between increased inferior frontal gyrus recruitment during food-cueexposure and sustained weight loss.Future directionsOne obvious difference between BED and addictive disorders is the role of the substance in theaddictive cycle. Humans are dependent on food for survival. While substantial addiction research isdevoted to examining molecular mechanisms of drugs on reward neurocircuitry, the effect of food onthese brain regions is less clear. It has been posited that high-fat, -salt and -sugar combinationsfound in many processed foods may more closely resemble a drug and hijack reward

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Neurobiological Underpinnings of Obesity and Addiction: A Focus on Binge Eating Disorder and Implications for TreatmentPublished on Psychiatric Times(http://www.psychiatrictimes.com)

neurocircuitry.39,40 Food-drug boundaries may be blurry, since multiple addictive products arederived from natural products; for example, alcohol, an addictive substance, is a natural productfrom ripe and fermenting grapes that also contains nutrients and calories. More research isnecessary for understanding how the hyperpalatability of certain foods may contribute to BEDdevelopment.Given the general availability of hyperpalatable foods, some researchers suggest that intermittentaccess rather than the specific nutritional content of food may be a key factor in the development ofbingeing behavior.41 Nonetheless, animal models suggest an interaction between the accessschedule and particularly palatable substances (eg, sugar), since repeated intermittent access tostandard food does not necessarily develop into binge eating.42

The escalation of binge eating episodes in BED is another behavioral trait that parallels addictivebehaviors. In humans, the shift from overeating to BED may result from dopaminergic alterationssimilar to those seen in addiction. It is noteworthy that PET studies of persons with BED reporteddopamine transmission alterations in the dorsal rather than ventral striatum. While the ventralstriatum has been implicated in food-cue reward as well as drug-cue reward, the dorsal striatum hasbeen implicated in habit formation and reinforcement of action. However, data also link the dorsalstriatum to reward processing in addictions.43

Given the different patterns of connectivity of dorsal and ventral striatum, it will be important tounderstand how ventral and dorsal striatum contribute to BED and how dopaminergic processes maybe involved. A challenging but important future direction will be understanding the neurobiology ofintermittent access to hyperpalatable foods and how eating restraint may lead to bingeing.To date, the handful of imaging studies conducted in persons with BED already demonstratedivergent neural substrates of this condition relative to other forms of disordered eating and obesity,substantiating the diagnostic autonomy of BED. This research is also beginning to demonstrate howspecific subgroups of obese individuals show neurocircuitry alterations similar to those in otherpopulations characterized by problems with impulse control. Understanding the neurobiologicalunderpinnings of core BED features may clarify distinct and/or overlapping mechanisms withaddictive disorders and guide treatment development efforts.Acknowledgments—This work was supported by P20 DA027844, K24 DK070052, CASAColumbia,and the National Center for Responsible Gaming.

CME POST-TESTPost-tests, credit request forms, and activity evaluations must be completed online atwww.cmeoutfitters.com/PT (requires free account activation), and participants can print theircertificate or statement of credit immediately (80% pass rate required). This Web site supports allbrowsers except Internet Explorer for Mac. For complete technical requirements and privacy policy,visit www.neurosciencecme.com/technical.asp.PLEASE NOTE THAT THE POST-TEST IS AVAILABLE ONLINE ONLY ON THE 20TH OF THEMONTH OF ACTIVITY ISSUE AND FOR A YEAR AFTER.

Neurobiological Underpinnings of Obesity andAddiction: A Focus on Bin...

Disclosures: Iris M. Balodis, PhD,1 Carlos M. Grilo, PhD,1-3 and Marc N. Potenza, PhD, MD 1-5

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Neurobiological Underpinnings of Obesity and Addiction: A Focus on Binge Eating Disorder and Implications for TreatmentPublished on Psychiatric Times(http://www.psychiatrictimes.com)

1Department of Psychiatry, Yale University School of Medicine, New Haven, Conn; 2Department ofPsychology, Yale University School of Medicine; 3CASAColumbia, Yale University School of Medicine; 4Child Study Center, Yale University School of Medicine; 5Department of Neurobiology, YaleUniversity School of Medicine References: 1. Hudson JI, Hiripi E, Pope HG Jr, Kessler RC. The prevalence and correlates of eating disorders inthe National Comorbidity Survey Replication [published correction appears in Biol Psychiatry.2012;72:164]. Biol Psychiatry. 2007;61:348-358.

2. Kessler RC, Berglund PA, Chiu WT, et al. The prevalence and correlates of binge eating disorder inthe World Health Organization World Mental Health Surveys. Biol Psychiatry. 2013;73:904-914.

3. Karhunen LJ, Vanninen EJ, Kuikka JT, et al. Regional cerebral blood flow during exposure to food inobese binge eating women. Psychiatry Res. 2000;99:29-42.

4. Geliebter A, Ladell T, Logan M, et al. Responsivity to food stimuli in obese and lean binge eatersusing functional MRI. Appetite. 2006;46:31-35.

5. Schienle A, Schäfer A, Hermann A, Vaitl D. Binge-eating disorder: reward sensitivity and brainactivation to images of food. Biol Psychiatry. 2009;65:654-661.

6. Levy DJ, Glimcher PW. The root of all value: a neural common currency for choice. Curr OpinNeurobiol. 2012;22:1027-1038.

7. Schäfer A, Vaitl D, Schienle A. Regional grey matter volume abnormalities in bulimia nervosa andbinge-eating disorder. Neuroimage. 2010;50:639-643.

8. Franklin TR, Acton PD, Maldjian JA, et al. Decreased gray matter concentration in the insular,orbitofrontal, cingulate, and temporal cortices of cocaine patients. Biol Psychiatry. 2002;51:134-142.

9. Tanabe J, Tregellas JR, Dalwani M, et al. Medial orbitofrontal cortex gray matter is reduced inabstinent substance-dependent individuals. Biol Psychiatry. 2009;65:160-164.

10. Filbey FM, Myers US, Dewitt S. Reward circuit function in high BMI individuals with compulsiveovereating: similarities with addiction. Neuroimage. 2012;63:1800-1806.

11. Breiter HC, Aharon I, Kahneman D, et al. Functional imaging of neural responses to expectancyand experience of monetary gains and losses. Neuron. 2001;30:619-639.

12. Knutson B, Adams CM, Fong GW, Hommer D. Anticipation of increasing monetary rewardselectively recruits nucleus accumbens. J Neurosci. 2001;21:RC159.

13. Knutson B, Fong GW, Adams CM, et al. Dissociation of reward anticipation and outcome withevent-related fMRI. Neuroreport. 2001;12:3683-3687.

14. Risinger RC, Salmeron BJ, Ross TJ, et al. Neural correlates of high and craving during cocaineself-administration using BOLD fMRI. Neuroimage. 2005;26:1097-1108.

15. Breiter HC, Gollub RL, Weisskoff RM, et al. Acute effects of cocaine on human brain activity andemotion. Neuron. 1997;19:591-611.

16. Balodis IM, Kober H, Worhunsky PD, et al. Monetary reward processing in obese individuals withand without binge eating disorder. Biol Psychiatry. 2013;73:877-886.

17. Balodis IM, Kober H, Worhunsky PD, et al. Diminished frontostriatal activity during processing ofmonetary rewards and losses in pathological gambling. Biol Psychiatry. 2012;71:749-757.

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Neurobiological Underpinnings of Obesity and Addiction: A Focus on Binge Eating Disorder and Implications for TreatmentPublished on Psychiatric Times(http://www.psychiatrictimes.com)

18. Andrews MM, Meda SA, Thomas AD, et al. Individuals family history positive for alcoholism showfunctional magnetic resonance imaging differences in reward sensitivity that are related toimpulsivity factors. Biol Psychiatry. 2011;69:675-683.

19. Weygandt M, Schaefer A, Schienle A, Haynes JD. Diagnosing different binge-eating disordersbased on reward-related brain activation patterns. Hum Brain Mapp. 2012;33:2135-2146.

20. Nestor LJ, Ghahremani DG, Monterosso J, London ED. Prefrontal hypoactivation during cognitivecontrol in early abstinent methamphetamine-dependent subjects. Psychiatry Res. 2011;194:287-295.

21. Salo R, Ursu S, Buonocore MH, et al. Impaired prefrontal cortical function and disrupted adaptivecognitive control in methamphetamine abusers: a functional magnetic resonance imaging study. BiolPsychiatry. 2009;65:706-709.

22. Balodis IM, Molina ND, Kober H, et al. Divergent neural substrates of inhibitory control in bingeeating disorder relative to other manifestations of obesity. Obesity (Silver Spring). 2013;21:367-377.

23. Volpicelli JR, Alterman AI, Hayashida M, O’Brien CP. Naltrexone in the treatment of alcoholdependence. Arch Gen Psychiatry. 1992;49:876-880.

24. Drewnowski A, Krahn DD, Demitrack MA, et al. Taste responses and preferences for sweethigh-fat foods: evidence for opioid involvement. Physiol Behav. 1992;51:371-379.

25. Ziauddeen H, Chamberlain SR, Nathan PJ, et al. Effects of the mu-opioid receptor antagonistGSK1521498 on hedonic and consummatory eating behaviour: a proof of mechanism study inbinge-eating obese subjects [published correction appears in Mol Psychiatry. 2014;19:1341]. MolPsychiatry. 2013;18:1287-1293.

26. Chamberlain SR, Mogg K, Bradley BP, et al. Effects of mu opioid receptor antagonism oncognition in obese binge-eating individuals. Psychopharmacology (Berl). 2012;224:501-509.

27. Cambridge VC, Ziauddeen H, Nathan PJ, et al. Neural and behavioral effects of a novel mu opioidreceptor antagonist in binge-eating obese people. Biol Psychiatry. 2013;73:887-894.

28. O’Malley SS, Sinha R, Grilo CM, et al. Naltrexone and cognitive behavioral coping skills therapyfor the treatment of alcohol drinking and eating disorder features in alcohol-dependent women: arandomized controlled trial. Alcohol Clin Exp Res. 2007;31:625-634.

29. Wang GJ, Geliebter A, Volkow ND, et al. Enhanced striatal dopamine release during foodstimulation in binge eating disorder. Obesity (Silver Spring). 2011;19:1601-1608.

30. Reas DL, Grilo CM. Review and meta-analysis of pharmacotherapy for binge-eating disorder. Obesity (Silver Spring). 2008;16:2024-2038.

31. Reas DL, Grilo CM. Current and emerging drug treatments for binge eating disorder. Expert OpinEmerg Drugs. 2014;19:99-142.

32. McElroy SL, Hudson JI, Capece JA, et al; Topiramate Binge Eating Disorder Research Group.Topiramate for the treatment of binge eating disorder associated with obesity: a placebo-controlledstudy. Biol Psychiatry. 2007;61:1039-1048.

33. McElroy SL, Hudson JI, Mitchell JE, et al. Efficacy and safety of lisdexamfetamine for treatment ofadults with moderate to severe binge-eating disorder: a randomized clinical trial. JAMA Psychiatry.2015;72:235-246.

34. Iacovino JM, Gredysa DM, Altman M, Wilfley DE. Psychological treatments for binge eatingdisorder. Curr Psychiatry Rep. 2012;14:432-446.

35. Wilson GT, Wilfley DE, Agras WS, Bryson SW. Psychological treatments of binge eating disorder.

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Neurobiological Underpinnings of Obesity and Addiction: A Focus on Binge Eating Disorder and Implications for TreatmentPublished on Psychiatric Times(http://www.psychiatrictimes.com)

Arch Gen Psychiatry. 2010;67:94-101.

36. Grilo CM, Masheb RM, Wilson GT, et al. Cognitive-behavioral therapy, behavioral weight loss, andsequential treatment for obese patients with binge-eating disorder: a randomized controlled trial. JConsult Clin Psychol. 2011;79:675-685.

37. Balodis IM, Grilo CM, Kober H, et al. A pilot study linking reduced fronto-striatal recruitmentduring reward processing to persistent bingeing following treatment for binge-eating disorder. Int JEat Disord. 2014;47:376-384.

38. McCaffery JM, Haley AP, Sweet LH, et al. Differential functional magnetic resonance imagingresponse to food pictures in successful weight-loss maintainers relative to normal-weight and obesecontrols. Am J Clin Nutr. 2009;90:928-934.

39. Kauer JA, Malenka RC. Synaptic plasticity and addiction. Nat Rev Neurosci. 2007;8:844-858.

40. Kenny PJ, Voren G, Johnson PM. Dopamine D2 receptors and striatopallidal transmission inaddiction and obesity. Curr Opin Neurobiol. 2013;23:535-538.

41. Smith DG, Robbins TW. The neurobiological underpinnings of obesity and binge eating: arationale for adopting the food addiction model. Biol Psychiatry. 2013;73:804-810.

42. Bello NT, Guarda AS, Terrillion CE, et al. Repeated binge access to a palatable food alters feedingbehavior, hormone profile, and hindbrain C-Fos responses to a test meal in adult male rats. Am JPhysiol Regul Integr Comp Physiol. 2009;297:R622-R631.

43. Patel KT, Stevens MC, Meda SA, et al. Robust changes in reward circuitry during reward loss incurrent and former cocaine users during performance of a monetary incentive delay task. BiolPsychiatry. 2013;74:529-537. Source URL: http://www.psychiatrictimes.com/neurobiological-underpinnings-obesity-and-addiction-focus-binge-eating-disorder-and-implications?rememberme=1&ts=29092015

Links:[1] http://www.psychiatrictimes.com/cme[2] http://www.psychiatrictimes.com/authors/iris-m-balodis-phd[3] http://www.psychiatrictimes.com/authors/carlos-m-grilo-phd[4] http://www.psychiatrictimes.com/authors/marc-n-potenza-phd-md

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