Exposure therapy in eating disorders revisited

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Neuroscience and Biobehavioral Reviews 37 (2013) 193–208

Contents lists available at SciVerse ScienceDirect

Neuroscience and Biobehavioral Reviews

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xposure therapy in eating disorders revisited

ntonia Koskina ∗, Iain C. Campbell, Ulrike Schmidtection of Eating Disorders (PO59), Institute of Psychiatry, King’s College London, De Crespigny Park, London SE5 8AF, United Kingdom

r t i c l e i n f o

rticle history:eceived 24 August 2012eceived in revised form0 November 2012ccepted 21 November 2012

a b s t r a c t

Exposure therapy is a widely used and effective form of treatment in anxiety disorders and addictionsbut evidence for its usefulness in eating disorders (ED) is inconsistent. This paper systematically reviewsthe literature on the use of exposure therapy in ED, the theory underpinning its use, and the deficits incurrent knowledge. Databases were searched to 2012. In addition, potential improvements in the useof exposure techniques in ED are considered by drawing upon theory and research involving neuro-pharmacology, basic and clinical neuroscience, contemporary behavioural and neurobiological research,

eywords:ating disordersxposureearningnorexia nervosaulimia nervosa

and technologies such as virtual reality (VR).© 2012 Elsevier Ltd. All rights reserved.

irtual reality

ontents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1932. Exposure techniques in ED: a review of the evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194

2.1. In vivo food exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1952.1.1. Exposure with response prevention of purging (ERP-P) for BN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1952.1.2. Exposure with response prevention of bingeing (ERP-B) for BN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1952.1.3. Food exposure in AN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195

2.2. In vivo body image exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1982.3. Food and body image exposure using virtual reality (VR) protocols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200

3. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2003.1. Main findings from the systematic review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2003.2. Extinction, learning theory and their relevance to exposure treatment in ED . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2013.3. Use of a fear extinction model: neural correlates, clinical applications and limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2023.4. Integration of animal and clinical findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2023.5. Integration of findings from basic and clinical neuroscience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2023.6. Use of pharmacological agents as an adjunct to exposure treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2023.7. Use of neuromodulation as an adjunct to exposure treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203

4. Recommendations for clinical practice and future research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2035. Summary and conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204

Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205

. Introduction syndromes (eating disorder not otherwise specified; EDNOS) are

The eating disorders (ED), anorexia nervosa (AN), bulimia ner-osa (BN), binge eating disorder (BED) and related partial or mixed

∗ Corresponding author. Tel.: +44 7801 954 151; fax: +44 2078 480 182.E-mail address: [email protected] (A. Koskina).

149-7634/$ – see front matter © 2012 Elsevier Ltd. All rights reserved.ttp://dx.doi.org/10.1016/j.neubiorev.2012.11.010

disorders with significant physical and psychosocial disability andfrequent relapse (Treasure et al., 2010a). Whilst AN has been docu-mented historically and cross-culturally, BN and related disordersare seen as modern Western phenomena observed in cultures
where food is plentiful and – against a societal trend of growingobesity – slimness is highly valued (Habermas, 2005; Schmidt andTreasure, 1993; Silverman, 1988).
dx.doi.org/10.1016/j.neubiorev.2012.11.010

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inclusion. Although imaginal exposure techniques were searchedfor, exposure in vivo or exposure using virtual reality technolo-gies appeared to be the only methods cited in the literature. Search

1 Kamboj et al. (2011) point out that the terms extinction and habituation areused interchangeably in the literature: “However ‘extinction’ is perhaps more clearlydefined as a neurobiological process involving reduction in the conditioned responsefollowing repeated exposure to the conditioned stimulus, with concurrent reduc-tion in neural activity in central nervous structures in which the CS–CR and/orCS–CS relationships are represented. Habituation on the other hand, also involvesresponsiveness with repeated stimulation, but in addition to the neurobiologicaland behavioural changes seen in extinction, may also encompass confounding fac-

94 A. Koskina et al. / Neuroscience and B

There is an ongoing debate on classification (Hebebrand andulik, 2010; Knoll et al., 2011) but ED can be conceptualised as beingn a spectrum of over- and under-eating and this is associated withltered weight and with altered food associated reward. This mayanifest itself in a number of ways, for example as a dread of food,

r a phobic avoidance of eating, fullness or fatness. Alternatively, itay be manifest as an excessive desire to eat, overeating of highly

alatable foods or a mixture of both dread and desire and over- andnder-consumption. In addition, an overvaluation of body shapend weight is usually present (APA, 2000) and in AN, there is oftenignificant hyperactivity (Hebebrand and Bulik, 2010).

The aetiology of ED is complex, with overlapping and distinctisk factors for different types of ED, including sociocultural andther environmental factors, temperamental, endocrine, develop-ental, genetic and epigenetic factors (Becker, 2007; Becker et al.,

005; Campbell et al., 2011; Connan et al., 2007; Day et al., 2011;airburn et al., 1999, 1998, 1997; Jacobi et al., 2004; Monteleone andaj, 2008; Pike et al., 2008; Pjetri et al., 2012; Stice, 2002; Stice et al.,

005; Striegel-Moore et al., 2007, 2005) and gene–environmentnteractions (GxE) (Karwautz et al., 2011).

Effective treatments exist for some of the ED. Cognitiveehavioural therapy (CBT) is the treatment of choice for adoles-ents and adults with BN and BED, with good acceptability andfficacy (Fairburn et al., 2009; Hay and Claudino, 2010; Schmidtt al., 2007). However, if CBT fails, the best course of action isomewhat unclear. Whilst family-based interventions are generallyecommended in the case of adolescents with AN (Lock, 2011; NICE,004), for adults with AN, there is no gold-standard treatment, andutcomes are poor (Schmidt et al., 2012). Thus, novel approacheso treatment are needed. These require an improved understand-ng of the neurobiological and psychological underpinnings of EDnd this has greatly improved in the last decade due to advancesn neuroimaging, in learning theory, in new pharmacological andhysiological interventions and from information from animaltudies.

Among the many factors that influence food intake in humansnd animals, learning and conditioning (Pavlovian and instru-ental) processes have an important role in determining food

references and when, how often, and how much food is consumedBouton, 2011; Epstein et al., 2009). Thus, distinct environmentalues (or specific contexts) can override homeostatic signals andtimulate or inhibit eating in the sated or hungry state. Rodent mod-ls of such cue-induced feeding or feeding inhibition have beeneveloped (Petrovich, 2011). Inter-individual differences in bothear and appetitive conditioning and ability to extinguish learnedssociations are to some extent, heritable (Malkki et al., 2010, 2011;ineka and Oehlberg, 2008). Interestingly, in the context of ED, sex

ifferences have also been noted with fear-induced feeding cessa-ion being more difficult to extinguish in female rather than maleats (Petrovich and Lougee, 2011).

Conditioning processes have been proposed to play an impor-ant role in the development and maintenance of ED, viaonditioned food avoidance (Strober, 2004; Treasure et al., 2011) oronditioned (excessive) food reward (Bouton, 2011). Traits whichre common in ED, such as anxiety and behavioural inhibition seemo facilitate acquisition of conditioned fears and may also accountor inter-individual differences in extinction learning (Mineka andehlberg, 2008). Indeed, an early report of AN described self-onditioned food avoidance in a patient who imagined putrid cat’sudding when pressed to eat, thus inducing vomiting (Hewett,873). Studies in rodents have found that experience of activ-

ty based anorexia (ABA) in adolescence leads to anxiety-like
ehaviour in adulthood (Kinzig and Hargrave, 2010), and enhancedonditioned taste aversion learning (Liang et al., 2011).
Acquisition of conditioned reward and conditioned fear areased on distinct neural circuitry and neurochemistry, but

avioral Reviews 37 (2013) 193–208

common final pathways seem to be involved in the extinction1

of both processes, with pre-frontal cortex glutamatergic path-ways having a central role (for review, see Kaplan et al., 2011).Exposure treatment is a clinical intervention based on the prin-ciples of Pavlovian conditioning and which targets conditionedfear responses and conditioned reward and aims to reduce orextinguish these responses. A large evidence base supports theefficacy of exposure treatment in anxiety disorders, including spe-cific phobias (Wolitzky-Taylor et al., 2008), panic disorder (Westenand Morrison, 2001), obsessive compulsive disorder (Foa et al.,2005; Franklin et al., 2000) and post-traumatic stress disorder(Cukor et al., 2010; Powers et al., 2010; Rothbaum and Schwartz,2002). Exposure treatment in anxiety disorders is based on thepremise that phobic anxiety and avoidance are typically cue con-trolled (Jansen et al., 1992). Using graded exposure to fear-inducingstimuli, techniques attempt to break the pattern of avoidance thatstrengthens the fear response. The patient learns by experience thatthe feared consequences do not occur and develops new non-fearassociations with the stimuli (Abramowitz et al., 2010). Exposurehas also been used with partial success to minimise craving andrelapse in substance abuse disorders (Kaplan et al., 2011).

A number of studies have applied exposure treatments in ED andthere is a resurgence of interest in this method. This paper criticallyreviews the evidence on the use of exposure techniques as appliedto ED, and identifies deficits in knowledge. In addition, it discusseshow the efficacy of exposure therapy for ED might be improvedby drawing upon theory and research from neuropharmacology,contemporary learning theory, and technologies that use virtualreality. Recommendations for research are also made.

2. Exposure techniques in ED: a review of the evidence

PubMed and Web of Science databases were searched to 2012.Search terms included: Eating disorders, anorexia nervosa, bulimianervosa, binge eating disorder, cue exposure, response preven-tion, exposure therapy, imagined exposure and mirror exposure. Toensure no significant reference was overlooked, the specific termsand Boolean operators included: (exposure or exposure therapy orcue exposure or response prevention or mirror exposure or imag-ined exposure or imagery exposure) and (eating disorders or anorexianervosa or bulimia nervosa or binge eating disorder). This search pro-duced 708 results. Abstracts were scanned for their suitability andstudies were included if they involved the application of expo-sure techniques in an ED sample either alone, or in comparisonto another treatment or control condition. Studies from an earlyreview (Carter and Bulik, 1994) were gathered and included, assome of these publications did not appear in any of the investigatedsearch engines. Overall, 31 studies were considered suitable for

tors such as fatigue and ‘stimulus’ ‘satiation,’ especially in human studies (Grovesand Thompson, 1970).“Whilst we agree with Kamboj et al.’s definition for pragmaticreasons, we decided to use the two terms interchangeably here, as we review someanimal literature where extinction is the term commonly used and human literaturewhere the term habituation is preferred.

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esults yielded two main categories of exposure techniques: Foodxposure and Body Image Exposure.

.1. In vivo food exposure

Food exposure for people with BN and/or AN binge/purge sub-ype (ANBP) usually focuses on the prevention of bingeing orurging whereas, for those with the restrictive subtype of AN (ANR),raded food exposure is used to introduce the consumption ofeared foods. These are described below.

.1.1. Exposure with response prevention of purging (ERP-P) forN

The earliest proponents of exposure techniques in ED usedxposure with Response Prevention (of purging) (ERP) as a treat-ent for BN based on an ‘anxiety reduction model’ (Rosen and

eitenberg, 1982): in this, eating elicits fear of weight gain andurging reduces the associated anxiety, analogous to the rolef excessive hand washing or checking in OCD. Thus, purgingehaviours negatively reinforce binge eating by removing the fearf weight gain. ERP for purging (ERP-P) is used to gradually exposeatients with BN or ANBP to feared food cues and prevent vomitingfter consumption, thereby extinguishing anxiety via habituation.he therapist remains with the patient until the urge to vomit hasassed, during which time the therapist elicits and challenges dis-orted beliefs (Leitenberg et al., 1988; Rosen and Leitenberg, 1982).RP-P has also been conceptualised within a social learning theoryramework: Wilson et al. (1986) proposed that ERP-P enhances theatient’s sense of self-efficacy and bolsters their ability to cope withigh-risk situations.

Nine studies applying ERP-P techniques were identified (oneingle case study, two case series, one cross-over study, one non-andomised controlled trial and four RCTs). Early case series,ross-over and controlled studies provided proof of concept forRP-P by demonstrating a reduction in vomiting at post-treatmentGiles et al., 1985; Gray and Hoage, 1990; Leitenberg et al., 1984;osen and Leitenberg, 1982; Rossiter and Wilson, 1985). However,he majority of these studies did not include any data on changen bingeing frequency and the proportion of participants who metriteria for BN at treatment completion and follow-up is not known.andomised controlled trials (RCT) are detailed in Table 1 . Datahowed ERP-P to be superior (in terms of reduction of vomiting)ompared to waiting list, but not to CBT (Leitenberg et al., 1988), noras the addition of ERP-P to CBT (Agras et al., 1989; Leitenberg et al.,

988), or to cognitive restructuring (Wilson et al., 1991) superioro these interventions alone. All four RCTs were small and probablynder-powered. Where reported, acceptability of ERP-P appearedo be reasonable, with control or comparison treatment conditionsxperiencing similar or higher attrition rates than ERP-P (Wilsont al. (1986): 25% of control group; 22% of ERP group; Agras et al.1989), 5.9% of ERP-P group; 22.7% of CBT group; 15.8% of self-

onitoring condition and 5.3% of the wait list). In all the reviewedtudies, ERP-P involved eliciting and challenging distorted cogni-ions during exposure, an approach that is largely considered partf cognitive treatment. This makes it difficult to attribute findingsolely to the effect of exposure.

Whilst methodological limitations permeate these early stud-es, there are also some conceptual concerns about the theoreticalasis of ERP-P. Firstly, although it is hypothesised that eating inRP-P induces an urge to purge, food consumption could also pro-uce an urge to binge, via priming, or indeed, an urge to restrict

ntake (Carter and Bulik, 1994). It is unclear therefore, which spe-
ific urges arise during ERP-P, as urges to binge and/or to restrictre not usually measured as outcome variables. Secondly, theres concern about the emphasis on vomiting as a central main-aining factor in BN (Carter and Bulik, 1994; Schmidt and Marks,
avioral Reviews 37 (2013) 193–208 195

1989) because a subgroup of individuals with BN, and those withBED, engage in binges without purging. The ERP-P model doesnot take into account the cues that precede bingeing, and placeslittle emphasis on binge eating as a maintaining factor in eat-ing disordered behaviour (Carter and Bulik, 1994). Lastly, ERP-P islogistically complex and time-consuming, and the need to organisebinge conditions for each patient in a naturalistic setting may limitits application.

2.1.2. Exposure with response prevention of bingeing (ERP-B) forBN

An alternative exposure technique that uses a classical con-ditioning model has been proposed (Jansen et al., 1992, 1989).Exposure with Response Prevention of Bingeing (ERP-B), alsonamed Cue Exposure, conceptualises excessive food intake (i.e.bingeing) as the unconditioned stimulus (US), and stimuli specifi-cally associated with binge-eating (e.g. the sight or taste of palatablefood, emotional states, or time of day) as the conditioned stimuli(CS). This model for binge eating hypothesises that if a CS predictsbingeing (US), and elicits physiological responses such as craving,then repeated or prolonged exposure to the CS in the absence ofthe US, will result in extinction of craving (Jansen et al., 1992,1989). ERP-B involves exposing patients to binge foods and pre-venting bingeing whilst the food is touched and smelled. Smallamounts may also be tasted to elicit or increase the urge to binge(Schmidt and Marks, 1988). Six studies were found to use ERP-Btechniques: one single case study (Jansen et al., 1989); four caseseries (Schmidt and Marks, 1988; Kennedy et al., 1995; Toro et al.,2003; Martinez-Mallen et al., 2007) and one non-randomised con-trolled trial (Jansen et al., 1992). Three studies evaluated both ERP-Pand ERP-B: one cross-over study (Schmidt and Marks, 1989), andtwo RCTs (Cooper and Steere, 1995; Bulik et al., 1998a). See Table 1for details of RCTs.

Early case studies and other non-RCT data on ERP-B appeared toyield positive results in terms of symptom reduction, and the proce-dure was well tolerated. It is also of note that some of these studiesshowed promising results in individuals who had had not improvedwith CBT or pharmacological treatments (Martinez-Mallen et al.,2007; Toro et al., 2003), suggesting that exposure treatment maybe of use as a second line treatment in these situations.

One small RCT compared CBT with a combination of ERP-P fol-lowed by ERP-B (Cooper and Steere, 1995). Whilst there was similarimprovement in both groups, only those treated with CBT main-tained their gains whereas those treated with exposure relapsed.One larger RCT (Bulik et al., 1998a) combined CBT sequentially witheither ERP-P, ERP-B, or a relaxation control condition. Post treat-ment and at a 3-year follow up there was no significant differencein outcome between groups (Carter et al., 2003). However, at a 5-year follow-up, both the ERP-P and ERP-B groups showed greaterBN symptom reduction than the condition which combined CBTwith relaxation, thus providing some evidence of a ‘conditionedinoculation’ in those who received exposure treatment (McIntoshet al., 2011) (Table 1).

2.1.3. Food exposure in ANStudies using food exposure techniques for treating people with

AN are relatively uncommon (Boutelle, 1998). Models have empha-sised the symptom overlaps between AN and anxiety disorders andsuggested that exposure and response prevention may be usefuldue to its established efficacy in anxiety disorders (Foa et al., 2005;Whittal et al., 2005). These models draw parallels between AN,OCD and phobic anxiety disorder, and propose that fear and anx-
iety are integral to the perpetuation of detrimental eating habits(Hildebrandt et al., 2010; Steinglass et al., 2011a). Specifically, pre-meal anxiety in AN is negatively correlated with subsequent foodintake (Steinglass et al., 2010). Exposure with response prevention

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Table 1RCTs using in vivo exposure in ED.

Author and Year Method Key outcomes Comments

InterventionType

Na Studypopulation

Exposure situation No ofsessions

Follow-up(FU)

Wilson et al. (1986) ERP-P 17 (12) BN sample;within 10%normal BMI

Random allocation to CRe orCR + ERP-P; treatment ingroups of 2/3. ERP-Pintroduced in session 4.

16 6 and 12months

CR + ERP-P significantlylowered bingeing andvomiting, increasedself-efficacy and dietarycontrol compared to CR; gainsmaintained at FU.

Small uncontrolled sample; nocomparison group data at FU assome psb went on to receiveERP-P; groups not given sameamount of CR each; no sigdifferences on many outcomes.

Leitenberg et al.(1988)

ERP-P 47 BN sample 4 groups: (1) ERP-P in clinic;(2) ERP-P multiple settings; (3)CBTd; (4) Wait list control.Treatment in groups of 3;exposure uniform for 6 weeks,then personalised.

24 6 months All treatment groups sigimproved on most outcomes.Slightly better outcomes onvomiting and food consumedin a test meal for the ERP-Pgroups.

Weak positive results for ERP;possible cross-contaminationbetween CBT and ERP-P; nomeasures of bingeing PTc orFU; group format meant lesstime for each ps.

Agras et al. (1989) ERP-P 77 (67) BN sample 4 groups: (1) CBT; (2)CBT + ERP-P; (3)Self-monitoring; (4) Wait listcontrol. Exposure began insession 7 and food intakeincreased over time.

14 6 months 3 treatment groups reducedpurging but CBT superior(80%); addition of ERP-P didnot enhance CBT and may havebeen deleterious.

Short time frame—ERP-Ppossibly displaced someessential elements of CBT;short 1 h sessions; unequalamounts of CBT—cannot assessthe ‘additive hypothesis.’

Wilson et al. (1991) ERP-P 22 BN sample,within 15%normal weightrange

RCT of (1) CBT, and (2)CBT + ERP-P. Exposureintroduced between sessions10 and 13.

20 3 and 12months

88% of CBT group stoppedbingeing PT and 63% ceasedpurging. For CBT + ERP-P,bingeing and purging cessationwere both at 67%. Gainsmaintained at FU.

Small sample; no wait listcontrol; unequal time allocatedto CBT so cannot addresswhether ERP-P hasadvantages; few exposuresessions; possiblecross-contamination with CBT.

Cooper and Steere(1995)

ERP-B andERP-P

27 BN sample 2 groups: (1) CBT withoutexposure, and (2) ERP-P (4sessions) and ERP-B (4sessions). Exposure groupreceived no cognitiverestructuring techniques.

19 12 months Both groups reduced bingeingand vomiting; at FU highrelapse in ERP group. Thosereceiving CBT maintainedgains.

Small sample, possible type IIerror; mix of ERP-P and ERP-Bshortens the duration of eachtechnique, may have reducedefficacy; possiblecross-contamination ofprocedures.

Bulik et al. (1998a) ERP-B andERP-P

135 (106) BN sample Ps received 8 sessions of CBTand were then randomised toeither (1) ERP-P, (2) ERP-B, or(3) Relaxation training.Exposure stimuli were tailoredto the individual. In ERP-Bparticipants did not consumeany binge food.

8 6 and 12month

ERP-B group had betteroutcomes on abstinence ofpurging PT (non-sig). ERP-B sigreduced anxiety towards bingecues, food restriction,depression and bodydissatisfaction. At 12 monthsERP-B decreased restriction.

Significant drop-out rate(N = 102 at 12 month FU);possible biased sample fromthe exclusion of those onmedication; no non-CBTcontrol group; possiblysubstantial improvementoccurring from 8 sessions ofCBT obscured effects ofexposure techniques.

Carter et al. (2003) ERP-B andERP-P

113 (92) Former BNSample (85% nocurrent dx)

3 year follow up from Buliket al. (1998a,b)

– 2 and 3years

85% of Ps had no current BN.No clear advantages for thosereceiving ERP-P or ERP-B overRelaxation, but treatmenteffects stable.

Drop-out and randomisationmeant only 92 completed CBT+behaviour therapy (ERP-P,ERP-B or Relaxation); nomention of whether psreceived other therapies inbetween FUs.

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Table 1 (Continued)


InterventionType

Na Studypopulation

Exposure situation No ofsessions

Follow-up(FU)

McIntosh et al.(2011)

ERP-B andERP-P

109 Former BNsample

5 year follow up from Buliket al. (1998a,b)

– 4 and 5years

Abstinence from bingeing sighigher for ERP-P and ERP-B(43% and 54%) than Relaxationgroup. Purging lower inexposure groups.

FU period uncontrolled forfurther treatment; exposuremay be most effective to thosenot responding to CBT; analysisincluded some ps who did notcomplete treatment.

Steinglass et al.(2007)

AN foodexposure

11 AN inpatients(5 ANbinge/purge; 4AN restrictive;2 atypical AN)

Food Exposure (withoutresponseprevention) ± D-Cycloserine(DCS) vs placebo. Two testmeals at baseline andpost-training. 4 training mealstwice-weekly: training mealsconsumed after receiving DCSor Placebo pill. Comparisongroup without exposure.

4 PT No differences betweenmedication groups in test ortraining meal consumption.Collapsing medication groupsshowed exposure groupincreased food intake frombaseline to final meal.

Difficult to determine specificcontribution of Exposure + DCS,other interventions ongoing onward; wide range of BMI; smallsample; comparison data takenfrom a previous study; no longterm FU; brief number ofsessions.

Delinsky andWilson (2006)

Body imageexposure

45 (41) Femalesw/weight andshape concerns(scoring >4 onEDE-Qsubscale)

Mirror exposure (ME) vsNon-directive body imagetreatment. ME: Ps asked tosystematically and mindfullydescribe themselves head totoe, without skipping ordwelling on features. Criticaland subjective terms werediscouraged. Second session inmore revealing clothing.

3 1 month Exposure group fared better PTand at FU on avoidance, bodychecking, weight and shapeconcerns, body dissatisfaction,dieting, depression andself-esteem.

Non-ED sample; noinformation on screening forother mental health problemsor history of ED. Possibleself-selected sample bias;unknown additive effect ofmindfulness techniques;drop-outs had sig. higher levelsof depression

a N: no. of participants; where possible those after drop-out is reported as (N).b Ps: participants.c PT: post treatment.d CBT: cognitive behavioural therapy.e CR: cognitive restructuring.

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or AN (AN-EXRP) uses graded food exposure to reduce avoidancend facilitate habituation to anxiety surrounding the anticipationnd ingestion of feared food (Steinglass et al., 2011a). AN-EXRPims to increase flexibility in food choice and caloric consumption,nd hence to improve the ability to maintain weight and preventelapse. One question in this context is whether the structured,egular and supervised eating of meals that is part of most special-st in-patient and day-care programmes for AN could be acting as

form of exposure therapy, i.e. by facilitating habituation to dif-erent high calorie foods. However, this may not be a particularffective form of exposure: in a study of in-patients with AN, eat-ng behaviour remained highly abnormal after treatment (Walsh,011), suggesting that for some patients the experience of eatinguring in-patient treatment could simply reinforce fears and nega-ive beliefs about eating. Another possibility is that the experiencef exposure to calorie dense food in inpatient settings does noteneralise well to naturalistic settings. This is considered further inur discussion but suggests a need for further investigation of theffects of regular eating in this clinical setting.

Three studies have used food exposure techniques in peopleith AN: one single case study (Boutelle, 1998), one case series

Steinglass et al., 2011b) and one RCT (Steinglass et al., 2007). Allsed AN-EXRP with some degree of success: however, two involvedtypical participants, i.e. one was a case study of a male with ANBoutelle, 1998), and the other treated a weight restored AN groupSteinglass et al., 2011b), Thus, the extent to which AN-EXRP isseful for treating people acutely ill with AN is unclear. The thirdtudy, a small RCT, investigated the effect of D-cycloserine (DCS)n food exposure (Steinglass et al., 2007) (see Table 1): it did notnvolve response prevention and was based on evidence that DCSnhances fear extinction during exposure therapy in anxiety dis-rders (Hofmann et al., 2006a; Kushner et al., 2007; Ressler et al.,004). DCS compared to placebo had no effect in any of the trainingr test meals (Steinglass et al., 2007). When the medication groupsere collapsed, some improvement was seen on final test meal

onsumption in those receiving exposure therapy (Steinglass et al.,007). However, interpretation of the findings is difficult becausehe exposure therapy was concurrent with inpatient treatment, andhe comparison group was from a previous study. Use of DCS tougment exposure techniques is discussed below.

In conclusion, the use of exposure therapy in AN is limited;tudies are preliminary, have small sample sizes, some potentialonfounds and weakly positive results. However, on theoreticalrounds this treatment appears to have potential, and is relativelycceptable to patients.

.2. In vivo body image exposure

Exposure techniques have been used to reduce body dissatis-action, body checking and avoidance in individuals with ED, andave been incorporated into therapeutic modalities such as CBT

or body image disturbance (Cash and Lavallee, 1997), mindfulnessased mirror exposure (Wilson, 2004), and cognitive dissonanceased mirror exposure for ED prevention programmes (Stice andresnell, 2007). Body image exposure techniques use mirrors orideos to encourage individuals to look systematically at each partf their bodies for an extended period of time, often whilst wearingight fitting clothing (Cash and Lavallee, 1997; Vocks et al., 2007,008). Exposure sessions, are often supplemented with additionalxposure homework assignments (Key et al., 2002; Rushford andstermeyer, 1997; Vocks et al., 2008).

Several mechanisms have been proposed to explain the changes
hat occur during these procedures. Information processing theo-ies suggest that negative self-schemas regarding one’s own bodyre activated when people with ED look in the mirror, and theseead to negative emotions and cognitions (Hilbert et al., 2002;

Vocks et al., 2007). As many individuals with ED overestimate theirown body dimensions and focus on perceived negative aspects(Jansen et al., 2005), exposure may allow corrective feedback tobe received regarding body size and this may lead to increasedbody acceptance, decreased fear of weight gain (Rushford andOstermeyer, 1997; Vocks et al., 2007) and sensitisation to positiveaspects of the body (Jansen et al., 2005). In terms of learning the-ory, looking systematically and repeatedly at each part of the bodyduring the exposure exercise is thought to reduce negative emo-tions via habituation (Vocks et al., 2008). It has been hypothesisedthat prolonged and repeated exposure weakens the associationbetween the conditioned stimulus of ‘seeing one’s own body’ andconditioned negative responses (Hilbert et al., 2002), and pre-vents avoidance (Wilson, 2004). Finally, from the perspective ofsocial learning theory, it has been proposed that the experience ofmirror exposure enhances self-efficacy as individuals learn theyare able to expose themselves to avoided and feared situations(Vocks et al., 2008). The extent to which these explanations con-tribute to the mechanisms of change during exposure is unclear,and it is likely that each is in operation to some degree. A recentstudy used a non-clinical sample of female undergraduates toexamine the relative effectiveness of three different approachesto mirror exposure: cognitive dissonance-based mirror exposure(in which participants described positive aspects of themselveswhen viewing their image), a mindfulness-based mirror exposure(in which participants practiced breathing meditation mindfulnesstechniques before completing mirror exposure), and a neutral non-judgmental approach to mirror exposure (Luethcke et al., 2011).All three variants of mirror exposure improved ED risk factors,but only the cognitive dissonance mirror exposure significantlyimproved levels of body image satisfaction. These findings suggestthat introducing a cognitive component to body image exposureexercises strengthens the effect of the technique; however, datashould be interpreted with caution as effect sizes were small inthis non-clinical sample. Comparisons of the different varieties ofmirror exposure have not been conducted in clinical samples.

Eight studies have investigated body image exposure tech-niques in patients with AN, BN or BED or in women with highweight and shape concerns. Of these, six are case-control stud-ies (Norris, 1984; Rushford and Ostermeyer, 1997; Hilbert et al.,2002; Tuschen-Caffier et al., 2003; Vocks et al., 2007, 2008), one isa non-randomised controlled trial (Key et al., 2002) and one an RCT(Delinsky and Wilson, 2006) (see Table 1).

Preliminary evidence from case control studies comparing EDwith healthy controls (HC) suggests that body image exposure leadsto short-term improvements on outcomes, such as low mood, self-esteem, body image, body checking, weight/shape concerns, etc.and in some of these studies to greater improvements in the EDgroup than in HC. It is of note that these studies usually just giveone or two exposure sessions and several report no follow-up data.At this stage, therefore, it is difficult to draw conclusions about therelative efficacy of body image approaches in different EDs, par-ticularly as no studies incorporated an ED control group conditioninto their design (all use healthy controls as a basis for comparison).One RCT in women with high shape and weight concerns comparedmindfulness-based body image exposure to a control treatmentinvolving non-directive body image treatment, and found the expo-sure condition to be superior to control treatment (Delinsky andWilson, 2006): applying the methodology used in this study toa clinical sample might increase insight into the efficacy of bodyimage exposure in ED.

A final point to consider when implementing mirror exposure
techniques is the variation that may occur within ED individualsdepending on the type of body image disturbance present and theassociated idiosyncratic safety-seeking behaviours. For example,some may engage in excessive checking behaviour to monitor their

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Table 2RCTs using virtual reality (VR) in ED.


Na Studypopulation

Procedure No of sessions Follow-up (FU)

Perpiná et al. (1999) 18 (13) 7 AN; 6 BN 2 groups: (1) Standardbody imagetreatment + relaxation; and(2) Standard body imagetreatment + VR. VR therapyincluded 6 settingsexposing ps to food andbody image.

8 sessions in Standardbody image condition + 6sessions of either VR orrelaxation

PTc VR group significantlyimproved levels of bodydissatisfaction, bodyavoidance and fear ofweight gain. No sigdifference on other EDsymptoms.

Small sample size, limitedpsb information given, i.e.age, sex; significant dropout; no FU.

Riva et al. (2002b) 20 Female BED Residential weight controltreatment with low caloriediet and physical trainingwith either: (1) VR sessionswith food and body imageexposure; or (2)psycho-nutritional groupsbased on CBTd principles.

(1) 7 VR sessions over 6.5weeks.(2) Nutritional groups 3xper week, 6.5 weeks.

PT VR group significantlyreduced levels of bodydissatisfaction, increasedself-efficacy andmotivation to change vscontrols.

Small preliminary trial;unequal amount oftherapeutic time allocatedto each condition; no FUdata.

Riva et al.(2003)

36 Female BED 3 groups: (1) Nutritional groupsweekly + low kcal diet and physicaltraining; (2) ECTe—treatment as withgroup 1 + weekly motivational groupsand bi-weekly VR sessions (Riva et al.,2002a, b); (3) CBT–treatment as group1 + weekly motivational groups andbiweekly individual CBT

(1) 5; (2) 5 nutritionalgroups, 5 motivationalgroups and 10 VR sessions;(3) 5 nutritional groups, 5motivational groups and10 CBT sessions

PT and 6month PT

PT: ECT showed superiorimprovement in bodyimage and acceptance,physical satisfaction andsocial skills. Weight lossand reduced bingeing in allconditions.

Small sample with low power;some weight gain shown in allgroups at 6 months PT; somecognitive techniques used inECT as well as CBT; noinformation on randomisationprocedures or blinding.

6 months: ECT group sigimproved on ED symptomsand body image; 77% freefrom bingeing (vs 56% ofgroup 3 and 22% of group1).

Riva et al. (2004) 120 68 obese;51 ED (36BED, 12 BNand 3EDNOS)

4 groups: (1)ECT + psychological andnutritional groups; (2)IndividualCBT + psychological andnutritional groups; (3)Nutritional grouptreatment only; or (4)Waiting list NB.ECT = 45 min sessions with15 minute VR exposure inwhich ps are immersed infood, body or interpersonalrelated environments.

(1) 10 ECT + 5 Psychologicalgroups and 4–6 nutritionalgroups(2) 10 CBT + 5 Psychologicaland 4–6 nutritional groups(3) 4–6 nutritional groups

PT Treatment groupsimproved significantly onmeasures of weight, eatingcontrol, bodydissatisfaction and otherpsychopathology. Littledifference between ECTand CBT groups. No changein waiting list group

Preliminary data with lowpower per group; noinformation onrandomisation; no primaryoutcome defined; noindication of blindingprocedures; drop-outunreported and no FU data;ECT and CBT used incombination with othertreatments; difficult toisolate effects of VR as briefexposure to VRET (15 min)and 30 min of cognitivetechniques.

a N: no. of participants; where possible those after drop-out is reported as (N).b Ps: participants.c PT: post treatment.d CBT: cognitive behavioural therapy.e ECT: experiential cognitive therapy.

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ody image, whilst others avoid their reflection. Most commonly,ndividuals with ED alternate between both checking and avoid-nce, depending on factors such as mood and changes in eating,nd weight (Shafran et al., 2004; Reas et al., 2005). Identifying theelevance of such safety behaviours before engaging in exposure ismportant in order to minimise their use and maximise the effec-iveness of the intervention.

.3. Food and body image exposure using virtual reality (VR)rotocols

A number of protocols using virtual environments have beeneveloped to provide alternative ways of delivering exposure ther-py (de Carvalho et al., 2010; Meyerbröker and Emmelkamp, 2010;erpiná et al., 2003). During virtual reality exposure therapy (VRET),atients are able to see fear or other salient (e.g. appetitive, orrug-cue) stimuli overlaid into a variety of visually realistic con-exts, thus allowing interaction with them in real time. To improveatients’ sensory experience, auditory, tactile and olfactory stimulian also be delivered (Bordnick et al., 2011). In ED, virtual kitchens,upermarkets and restaurants have been developed in which eat-ng behaviour can be assessed (Riva et al., 2002a, 2004). In addition,ody image exposure techniques have also been adapted for virtualnvironments, with technologies including virtual clothes shops,ymnasia, and swimming pools (Gutiérrez-Maldonado et al., 2010;iva et al., 2004).

Several studies have assessed the potency of virtual versus realife stimuli and of different virtual environments (salient or neu-ral) in eliciting emotional responses in ED patients. Details ofCTs are outlined in Table 2. A small study compared AN, BN andealthy participants’ response to different food cues (real food,irtual food and photographs) with regards to self-reported anx-ety and physiological response (heart rate, respiration and skinonductance). Food craving was not assessed. ED groups were indis-inguishable: they all showed higher anxiety levels in response toood stimuli than control participants and higher anxiety levels toeal and virtual foods compared to photographs, with no differ-nce between real and virtual food (Gorini et al., 2010). In a seriesf studies (Ferrer-García et al., 2009; Gutiérrez-Maldonado et al.,006, 2010) patients were randomly exposed to different virtualnvironments: an emotionally neutral living room, kitchens withigh and low calorie food, a restaurant with high and low calorie

ood, and a swimming pool. Anxiety and depression were measuredefore and after each environment. Patients showed higher anxi-ty in high calorie environments and the swimming pool, than ineutral environments with no differences between AN and BN par-icipants (Gutiérrez-Maldonado et al., 2006). Healthy controls onlyhowed increased levels of anxiety in the swimming pool (Ferrer-arcía et al., 2009). ED participants also experienced higher levelsf body image distortion and dissatisfaction after virtually eatingigh calorie foods compared to low-calorie foods, whereas controlarticipants’ body image was unchanged across different situationsGutiérrez-Maldonado et al., 2010). These studies suggest that vir-ual environments can effectively elicit ED-related fears.

Treatment studies using virtual food and body image exposurere emerging (see Table 2 for review of RCTs, and Ferrer-Garcíand Gutiérrez-Maldonado, 2012). A small early RCT (n = 18) in EDatients combined standard body image treatment with eitherelaxation or virtual reality therapy (exposure to food and bodymage), and the latter produced better outcomes (Perpiná et al.,999). Riva and colleagues have developed Experiential Cognitiveherapy (ECT) (Riva et al., 2004). This consists of ten 45 min sessions
ith a therapist. In each of these sessions, the patient enters dif-
erent virtual environments (food-, body- or interpersonal related)or 15 min and is encouraged to interact with them. Prior to this,he therapist introduces the particular environment and then, with


the patient explores their thoughts and feelings about this; at theend of the session, there is further reflection about the patient’sthoughts feelings and behaviours. These authors have conductedseveral RCTs (Riva et al., 2004, 2002b, 2003) mainly in patients withBED or obesity in which they compared ECT with CBT (Riva et al.,2004, 2003) or psychonutritional groups (Riva et al., 2002b): ECTwas as efficacious as the comparison treatment, and showed advan-tages on some outcome measures. These studies have a number ofmethodological limitations which make it difficult to interpret thefindings. Some of these concerns are the conduct and reporting ofthese RCTs (see Table 2 for details). Other problems concern thefact that ECT and CBT were combined with other treatment com-ponents. Finally, the VRET-component in ECT involved very briefexposure to different environments (15 min) coupled with 30 minsof cognitive techniques, thus making it difficult to identify the pri-mary therapeutic mechanism.

A case study (Cardi et al., 2012) used a non immersive virtualreality module as an add-on to the Maudsley Model of treatmentfor adults with AN (MANTRA) (Schmidt and Treasure, 2006), ina female outpatient who had not responded to CBT, pharmaco-logical treatment, or a recovery group. The technology is termed‘non-immersive’ as it does not use a head-mounted display. Themodule was delivered prior to MANTRA treatment, and used gradedexposure to feared foods in a virtual kitchen. Reductions in anx-iety levels, safety behaviours, and fears in relation to food wereseen on completion of the module. In addition, ED symptoms werereduced and body mass index (BMI, kg/m2) increased significantly(Cardi et al., 2012), suggesting it may be a beneficial adjunct to thetreatment of AN.

Overall, VRET appears to be a promising approach, but furtherevidence is needed to assess its therapeutic utility in ED. Poten-tial side-effects of VRET are limited, although some participantsmention nausea or drowsiness as a problem (de Carvalho et al.,2010). Other potential disadvantages are equipment costs (Rivaet al., 2002a) and the fact that it is not possible to personaliseVRET environments or alter exposure paradigms during a session,e.g. by introducing anxiety modulators (as one could do in real lifeexposure) (de Carvalho et al., 2010).

3. Discussion

This discussion considers the results of the systematic reviewand outlines some of the challenges to increasing the efficacy andacceptability of exposure treatment in ED. It proposes that if thetheoretical rationale associated with exposure treatment in ED wasimproved, the field would advance. In this context it considers howevidence from behavioural and neurobiological correlates of fearextinction, including concepts from learning theory, and a consid-eration of the neural circuitry underlying the ability to extinguishfear and clinical anxiety, might be of value. It also considers howpharmacological agents and neuromodulation may act as usefuladjuncts to exposure therapy. Lastly, it makes recommendationsfor clinical practice and research.

3.1. Main findings from the systematic review

Two different food exposure paradigms have been used in thetreatment of BN and to a much lesser extent for other ED thatinvolve binge eating (binge-purge AN): (a) cue exposure to thesight, smell and taste of binge foods and (b) exposure to eating(binge) foods and response prevention of vomiting. Most stud-
ies using these paradigms were conducted in the 1980s and 90s.Whilst there is a sizeable number of studies, with the exceptionof the trial by Bulik et al. (1998a) there is limited high quality evi-dence. For example, RCTs are small and hence underpowered and

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his, together with different exposure protocols, makes it difficulto draw definitive conclusions.

So what explains the decline in research in exposure therapyfter the initial surge of studies into its use for ED? An impor-ant reason is the emergence of CBT as the pre-eminent treatmentor bulimic eating disorders (Fairburn et al., 2009; NICE, 2004),ogether with the fact that early trials did not establish exposurereatments as superior to CBT or as improving outcomes if com-ined with CBT. Moreover, food exposure treatment is logisticallyifficult and time-consuming and attrition in some trials was high,uggesting that it is neither sufficiently acceptable nor practical.owever, the case series by Toro et al. (2003) and Martinez-Mallent al. (2007) which used cue exposure to food with good outcomesn patients who had not responded to CBT or medication suggesthat it is worth exploring cue-exposure as a second line treatment.se of exposure to food as a phobic stimulus in AN is in its infancy,ut given the lack of effective treatments for adults with AN, it isorth pursuing.

Body image exposure treatments appear promising, but highuality RCT-based evidence from clinical populations is lacking.iven that contemporary CBT treatments for bulimic disorders

nclude some focus on improving body image (which may or mayot have elements of body image exposure) it would be of inter-st to establish how much the inclusion of a body image exposureomponent adds to CBT for BN or related disorders.

Protocols utilising virtual reality technologies are a promisingethod for delivering exposure interventions: they appear to beell tolerated and, in addition, may act as an intermediary step for

ocialising patients to exposure prior to in vivo work.Many studies provide insufficient methodological details mak-

ng it difficult to determine the effective components of protocols.ecause of such issues, questions remain. For example, (a) howffective are exposure techniques in ED? (b) for whom are theyost effective? (c) how are they best applied, and (d) how do

hey work? In addition, as many of the reviewed studies com-ine exposure techniques with cognitive treatment techniques, it is

mportant to determine the contribution of exposure in the contextf more established treatments such as CBT.

On the basis of the findings above, it appears that the use ofxposure therapy in ED can be improved. It is proposed that thisill be helped if the theoretical, methodological and therapeuticnderpinnings of different exposure treatments in ED are betternderstood and integrated into practice. Some of the main areasor consideration are described below.

.2. Extinction, learning theory and their relevance to exposurereatment in ED

Learning theory suggests extinction is not simply a weakeningf the original CS-US association, or of forgetting, but is an activeearning process that devalues conditioned cues and contexts, and

asks or inhibits the original learning (Bouton, 2004; Myers andavis, 2007). Furthermore, during exposure to conditioned stimuli,oth extinction and reconsolidation can occur. Reconsolidation ishe preservation of the original memory after initial retrieval: it is

ost prominent when coincident with the conditioned stimuli, andeeds to be inhibited for effective extinction (Kaplan et al., 2011).ne problem with food exposure techniques (ERP-B and ERP-P) inD is that there is usually no attempt to disrupt the original fear-ul or conditioned appetitive memory from being reconsolidateduring exposure, i.e. no competing non-threat memory associa-ions are being formed to inhibit the negative thoughts and safety
ehaviours on the one hand, or craving/desire on the other, thatften arise in response to food. Therefore, during exposure, insteadf extinguishing fears or desires, the procedure may continuallyeconsolidate and strengthen existing conditioned responses to
avioral Reviews 37 (2013) 193–208 201

food. This may partly explain why re-feeding treatment of inpa-tients with AN, (who are often treated for long periods with regularmeals in structured and supervised conditions), does not reduceanxiety around food. In addition, reinforcement of fears and neg-ative meanings attached to food and weight gain may be coupledwith subtle cognitive avoidance manoeuvres or safety behaviours,which serve to prevent disconfirmation of a feared outcome andinterfere with treatment (Salkovskis, 1991). These factors may helpexplain why therapeutic effects of food exposure in ED are mod-erate, and often temporary. Knowledge from learning theory mayalso explain why body image exposure techniques, which inhibitnegative interpretations of one’s body and prevent avoidance, arerelatively more easily implemented and more successful (Vockset al., 2007, 2008).

Extinction learning is fragile and context-dependent, where‘context’ incorporates a variety of background stimuli, includingphysical environment, internal state, emotions, and time (Bouton,2004, 2011; Conklin and Tiffany, 2002). In addition, if conditionedfear or appetitive cues are encountered some time after extinc-tion, conditioned responding often spontaneously recovers as theconditioned stimulus is presented in a differing temporal context(Bouton, 2011; Havermans and Jansen, 2003; Myers and Davis,2007). Research on optimum timing for modifying fears has tar-geted the reconsolidation phase, which occurs over a brief period(∼6 h) after memories are reactivated/retrieved (Quirk et al., 2010;Schiller et al., 2010; Taylor et al., 2009). During this time period,stored information is labile and vulnerable to disruption, and fearmemories may be permanently ‘updated’ with new information(Quirk et al., 2010). Studies with healthy participants showedextinction training during the reconsolidation phase reduced fearspecific to the reactivated memory, which did not show sponta-neous recovery and did not return following a reinstating fearfulstimulus (Schiller et al., 2010). These data are encouraging, as thefear reduction lasted at least a year. It is unclear whether thereconsolidation-extinction technique can alter fear memories inpatients suffering from psychiatric disorders (Quirk et al., 2010),but it might be developed to ameliorate some of the high anxietyand emotional dysregulation found in ED patients.

Clinic or hospital environments may only weakly approximateto the reality of home, or other environments where individualsroutinely engage in ED behaviours. In addition, cognitive inflexi-bility and difficulties with set shifting seen in ED (e.g. Tchanturiaet al., 2012) may contribute to individuals having difficulties ingeneralising learning across situations. Exposure in a naturalisticsetting can be logistically difficult, expensive and time consum-ing (Bulik et al., 1998b) and thus, protocols may be insufficientlyefficacious to inhibit the original behaviours. Therefore, what is‘learned’ in treatment settings may not generalise to a home envi-ronment and individuals may remain vulnerable to relapse whenfaced with fearful or appetitive stimuli or stressors. Incorporatingretrieval cues into self-guided exposure may reduce the probabil-ity of context renewal and spontaneous recovery effects (Brooks,2000; Brooks and Bouton, 1993; Craske et al., 2008; Havermansand Jansen, 2003): retrieval cues are salient features of the extinc-tion environment that facilitate retrieval of the extinction learningwhen presented outside of the original context.

In terms of exposure cues in ED, (certainly in relation to foodcues), patients often experience complex mixed emotions includ-ing both dread and desire, the nature of which often changesrapidly. Furthermore, certain cues may only be relevant in certaincontexts e.g. binge associated food cues may not always inducethe urge to binge in an individual with BN. Rather, it may be
the presence of food in a combination of circumstances (e.g. lowmood, being alone, time of day, following several days of restric-tion, etc.). Thus, it is difficult to construct a universally applicableexposure protocol, based on a clear hierarchy. In people with AN,

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ood restriction, an emaciated body image and increased physi-al activity become highly rewarding (Keating, 2010): therefore, inhe future, variations of exposure paradigms are likely to be devel-ped that couple the conditioned reward response to more salutarytimuli (Zink and Weinberger, 2010).

.3. Use of a fear extinction model: neural correlates, clinicalpplications and limitations

There is evidence that neural circuits involving the amygdala,he ventromedial prefrontal cortex and hippocampus underlie thebility to extinguish fear and that clinical anxiety is associated withhanges in this circuitry. Evidence also suggests that a fear extinc-ion model is useful in predicting vulnerability to anxiety disordersnd treatment response although important caveats have beenoted in relation to its use as an explanatory model (Graham andilad, 2011). A fear extinction model does not capture all aspects of

linical anxiety, in particular cognitive components such as antici-atory anxiety and avoidance (Shin and Liberzon, 2010) and it doesot capture all aspects of any given anxiety disorder. For exam-le, the pathogenesis of obsessive compulsive disorder (OCD) is notell modelled by extinction and may be associated with differenteural circuits (Shin and Liberzon, 2010). Lastly, whilst extinction

s a key component of CBT for anxiety disorders, it is not the onlyechanism of therapeutic change. CBT also involves exposure to

he feared outcome itself, an aspect that may be better modelledy habituation paradigms (Storsve et al., 2010, 2012).

Whilst the caveats associated with using a fear extinction modelre noted, it is also noted that in ED (which has a higher incidencen females), there are studies showing that oestradiol modulatesrefrontal cortex and amygdala activity during fear extinction inomen and female rats (Zeidan et al., 2011). Moreover, a study

ssessing the involvement of oestradiol in fear extinction in alinically anxious group, found that in women with PTSD, lowestrogen levels were associated with impaired extinction learn-ng and greater symptom severity (Glover et al., 2012): if this ispplicable to AN, it may mean, for example that when ill and haveow circulating oestrogen levels, patients might be more resistanto fear extinction.

.4. Integration of animal and clinical findings

In anxiety disorders, integration of animal and human researchas increased understanding of behavioural aspects of extinction,he associated neural circuitry of fear acquisition and extinction,nd the clinical applications/limitations of the extinction modelcross different anxiety disorders (Graham and Milad, 2011; Miladnd Quirk, 2012). Animal models of ED exist. For example, thectivity-based anorexia (ABA) model has been extensively usedenetic studies related to responsivity to dietary restraint (Kas et al.,009; Gelegen et al., 2006, 2007, 2008): although anxiety is a com-onent of ABA, it has not been extensively studied. Models of bingeating have focused on behavioural and neurochemical signs ofddiction and hence are applicable to issues of learning reward andtress responsivity (Corwin et al., 2011; Oswald et al., 2011). It cane argued that exposure techniques in ED will be improved if more

ntegration can be achieved, between animal and clinical studies,ut as yet, this has not occurred to a substantial extent.

.5. Integration of findings from basic and clinical neuroscience

Recent years have seen a burgeoning of neuroscience data
elated to ED (Frank and Kaye, 2012; Kidd and Steinglass, 2012)nd the emergence of neurobiological models, in particular of ANe.g. Strober, 2004; Steinglass and Walsh, 2006; Kaye et al., 2009).hese models may seek to explain the core deficits in ED and the

strength of disorder-specific conditioned responses: in turn thismay impact on the efficacy of exposure interventions. For exam-ple, neuroimaging (fMRI; PET) studies suggest people with ED showfear-related brain responses to food and body cues, and alteredreward processing (Brooks et al., 2011). Alterations in some neu-ral circuits are reported to be present in the ill state and to persistafter recovery (Frank and Kaye, 2012): this is in accord with theidea that altered systems confer vulnerability to illness and arenot causal and may have implications for the duration of treat-ment and for its transferability to different contexts. As an example,people at risk of developing AN are proposed to have a trait alter-ation that increases activity in central serotonergic (5HT) systemsand that this is exacerbated by puberty-related hormonal changes(Kaye, 2008; Kaye et al., 2009). Increased synaptic 5-HT is hypothe-sised to be associated with anxiety and stress sensitivity and to leadto hyper-responsiveness in the amygdala to relevant environmen-tal stimuli, whether these are positive or threatening (Hariri et al.,2002). As synaptic 5-HT is proposed to be reduced by food restric-tion (which lowers dietary tryptophan, the 5-HT precursor) (Frankand Kaye, 2012), this provides a biological basis for the vicious cyclethat can arise in AN sufferers where eating exaggerates and foodrestriction reduces anxious mood, making eating and food expo-sure treatment highly aversive: this may have dietary implicationsthat should be addressed as part of treatment.

Neuropsychological studies in ED indicate that people with ANhave poor attention and concentration (Kidd and Steinglass, 2012),and difficulties in set shifting and global processing (Roberts et al.,2007; Lopez et al., 2009).They are also reported to have difficultylearning new behaviours (Steinglass and Walsh, 2006) and in extin-guishing old ones (Strober, 2004). A cognitive profile associatedwith BN is less well established but data suggest individuals havehigher levels of impulsivity (Kemps and Wilsdon, 2010), poorerdecision making abilities under conditions of risk, increased rewardsensitivity and in particular high sensitivity to ED related cues (Vanden Eynde et al., 2010, 2011).

Cognitive difficulties are most pronounced in in-patients withAN (e.g. Tchanturia and Lock, 2011), i.e. those with the mostsevere and chronic form of the illness. It is possible that weakcentral coherence in both AN and BN (Lopez et al., 2009) con-tributes to body image disturbance, as difficulties with globalprocessing may lead to a tendency to focus on specific disliked bodyparts when evaluating their shape or weight. This may have someexplanatory power for the efficacy of mirror exposure work in mod-ifying distorted body image. Such interventions encourage a moreglobal and comprehensive evaluation of the body, and discouragedetail-focused (local) processing of negatively evaluated body parts(Vocks et al., 2007, 2008).

3.6. Use of pharmacological agents as an adjunct to exposuretreatment

Extensive data indicates that pharmacological treatmentsimprove extinction learning (Bouton et al., 2008; Cukor et al.,2010; Davis et al., 2006; Hofmann, 2007; Kaplan et al., 2011;Marin et al., 2011; Norberg et al., 2008; Ressler et al., 2004;Vervliet, 2007). Preclinical studies report that extinction learn-ing can be blocked by N-methyl-d-aspartate (NMDA) glutamatereceptor antagonists, and facilitated with d-cycloserine (DCS), apartial agonist/antagonist at the NMDA receptor (Hofmann et al.,2006a; Norberg et al., 2008). DCS has been investigated as anadjunct to exposure techniques in anxiety disorders and addic-tions in both animal and human studies. Clinical trials have shown
that it enhances fear reduction during exposure therapy in anxietydisorders such as acrophobia (Ressler et al., 2004), social anxi-ety disorder (Hofmann et al., 2006b), OCD (Kushner et al., 2007)and panic disorder (Otto et al., 2010; Hofmann, 2007) possibly

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y promoting extinction learning to background context whichnhances contextual inhibition (Vervliet, 2007). The situation inddictions is less clear with some animal studies finding that DCSacilitates extinction of cocaine-self-administration (Thanos et al.,011) whilst others suggest that it potentiates reconsolidation ofocaine-associated memories (Lee et al., 2009). In humans, DCSombined with cue exposure therapy is reported to attenuateonditioned reactivity to smoking cues within sessions, but witho clear between session habituation (Santa Ana et al., 2009). Inocaine-dependent individuals, craving to cocaine cues increasedfter DCS administration (Price et al., 2009) and in a study of heavyon-dependent drinkers, it did not appear to enhance habituationo alcohol cue reactivity (Kamboj et al., 2011). Thus, the utility ofCS as an adjunct to exposure treatment of addictions is uncertainlthough the data from studies of anxiety are promising.

A preliminary placebo-controlled RCT has been conducted usingCS as an adjunct to food exposure in patients with AN (Steinglasst al., 2007). Food consumption increased in the participant grouput without a significant parallel improvement in pre- and post-eal anxiety, and no benefits resulted from the addition of DCS

ompared to placebo. The authors suggest that any drug effect mayave been obscured by the exposure intervention. The study was

imited by its small sample size, baseline differences between theCS and placebo groups, a highly variable BMI range of patientsnd a low number of exposure sessions. The latter may be impor-ant given that AN is more treatment resistant than height or socialhobia (on which the protocol was based). Duration of sessions maylso be important, because without prolonged exposure treatment,CS might enhance the reconsolidation of the fear memory and

ncrease anxiety (Lee et al., 2006; Vervliet, 2007). Lastly, Steinglasst al. (2007) note that their patients used ‘numerous cognitive strate-ies to avoid anxiety whilst eating’ and without the provision ofn extinction memory to inhibit these safety behaviours, this mayave further reconsolidated negative beliefs surrounding food. Fur-her studies of DCS as an adjunct to exposure in people with ED areeeded to address these issues. Finally, it is possible that other glu-amatergic medications may also be beneficial (Olive et al., 2011).

Other pharmacological agents of interest include GABA-B (�-mino-butyric acid B) receptor agonists (e.g. baclofen; sodiumxybate), which facilitate extinction learning of conditioned drugeward in animals [e.g. (Heinrichs et al., 2010)] and in animal andlinical trials of substance use, reduce intake, craving and anxietyfor reviews see Broft et al., 2007). In rats, baclofen suppresses bingeating of pure fat, but not sugar-bingeing (Berner et al., 2009). Smallpen-label studies of baclofen (Broft et al., 2007) and sodium oxy-ate (McElroy et al., 2011) in patients with BN or BED found thathey reduced bingeing and food craving.

Another pharmacological approach, which has yet to be exam-ned in ED, is the use of glucocorticoids (corticosterone in animalsnd cortisol, or its analogues, in humans). Glucocorticoids are pro-osed to have a dual action in that they may facilitate consolidationf extinction learning during exposure therapy, and impair retrievalf aversive memories (Bentz et al., 2010). Studies involving cortisolreatment in PTSD (Aerni et al., 2004) and phobias (de Quervaint al., 2011; Soravia et al., 2006) have shown promising resultsnd thus cortisol or its analogues may be of value in ED. In theontext of stress reduction and glucocorticoid use, it is noted thathere have also been studies involving propranolol (a beta adren-rgic antagonist) as a compound that may dull the emotional painssociated with the recall of upsetting experiences (Pitman et al.,002; Vaiva et al., 2003; Kindt et al., 2009). Finally, another avenueor adjunctive pharmacological treatment of extinction learning is
ia epigenetic regulation of gene expression (Kaplan et al., 2011).alproic acid (valproate), an anticonvulsant and a mood stabiliser,nhances extinction (but also acquisition and reconsolidation ofonditioned fear) possibly via its function as a histone deacetylase
avioral Reviews 37 (2013) 193–208 203

inhibitor (Bredy and Barad, 2008). To date, only case studies haveevaluated valproate in the treatment of bulimic disorders and theresults have been mixed (McElroy et al., 2009). However, it providesthe possibility of other epigenetic based interventions e.g. the useof S-adenosyl methionine (SAM) as a potential DNA methyl donorand of Vit B12 because of its involvement in SAM synthesis (Duthieet al., 2002; Mariman, 2008; Waterland and Michels, 2007): thisis of note as epigenetic changes have been implicated in memoryconsolidation (Roth and Sweatt, 2009; Campbell et al., 2011, forreview)

3.7. Use of neuromodulation as an adjunct to exposure treatment

Brain stimulation studies in animals and fMRI studies in humansconcur that the infralimbic region, which is a part of the ventrome-dial prefrontal cortex (vmPFC) is involved in fear extinction (Miladand Quirk, 2012; Phelps et al., 2004; Milad et al., 2007) and it hasbeen proposed that brain stimulation techniques be investigated asa means of facilitating extinction learning and make exposure moretolerable by reducing fear and anxiety (e.g. Rodriguez-Romagueraet al., 2012).

Transcranial magnetic stimulation (TMS) is a non-invasive tech-nique that modulates brain activity of a targeted area. In rats, highfrequency repetitive (r) TMS paired with exposure to a conditionedstimulus (CS) has been reported to facilitate fear extinction andthe effect persisted after 24 h without further stimulation (Baeket al., 2012). This suggests rTMS may augment exposure treatment.In clinical studies, our group has shown in sham-controlled ran-domised experiments that one-off high frequency i.e. stimulatory,rTMS applied to the left dorsolateral pre-frontal cortex (DLPFC)reduces food craving elicited by cue exposure to highly palatablefood stimuli healthy people with high levels of food craving andpeople with bulimic disorders (Uher et al., 2005; Van den Eyndeet al., 2010). In the bulimic patients, binge-eating was reduced overthe next 24 h in those who received real rather than sham rTMS.Moreover, in an uncontrolled case series in patients with AN, rTMS(again applied to the left DLPFC) reduced feeling full, feeling fatand feeling anxious, (i.e. core symptoms of AN) following expo-sure to visual and real food stimuli (Van den Eynde et al., 2011).These findings suggest that rTMS combined with exposure ther-apy is potentially useful for facilitating extinction memory in thetreatment of ED.

4. Recommendations for clinical practice and futureresearch

People with AN are highly anxious and avoidant and also arecognitively and behaviourally inflexible and rule bound. Cognitiveaspects of anxiety are prominent in ED (Sternheim et al., 2011,2012), particularly in AN (Startup et al., 2012). Dread of food, eat-ing and weight gain may border on delusional. AN typically isego-syntonic (Vitousek et al., 1998) with sufferers valuing theiremaciated state. These characteristics result in reluctance to changeand this makes a purely behavioural intervention, such as exposuretreatment challenging—especially, as in food exposure, where thefeared outcome (weight gain) is a treatment goal.

Exposure interventions in ED must be sufficiently robust todeal with issues arising from the complexities that characterisethese disorders. For the majority of patients, especially those withAN, this will mean that exposure interventions should be inte-grated into a broader treatment programme. As a minimum, it
should be established that patients are motivated to comply withexposure treatment. This may involve extensive preparatory workor a ‘pre-exposure intervention’, e.g. use of motivational inter-viewing or anxiety management techniques (including relaxation

2 iobehavioral Reviews 37 (2013) 193–208

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Box 1Recommendations for improving the efficacy of exposure ther-apy in ED

1. Preparatory work 2. Optimised exposureprotocols

1. Adjuncts to exposuretherapy

• Assessment ofsafety behavioursand idiosyncraticcognitivestrategies

• Naturalistic andpersonalised exposuresettings

• Further researchinvestigatingD-Cycloserine (DCS),glucocorticoids,GABA-B receptoragonists and valproicacid in ED

• MotivationalInterviewing

• Multiple contexts • Exploration of rTMSas an adjunct toexposure

• AnxietyManagement

• Graded exposure:Therapist led → self-guidedhomeworks

• CognitiveRemediationTherapy

• Include retrieval cues andindividualised exposurecues• Provide a non-threateningmemory to disruptreconsolidation, e.g.relaxation, vodcasts.• Use of virtualtechnologies


r cognitive techniques). In addition, prior to exposure treatment,here should be an investigation of idiosyncratic safety behaviourshat may prevent new learning. Another, albeit more time intensivend specialised option, may involve the use of cognitive remedia-ion therapy (CRT), which targets the neurocognitive deficits foundn ED: this aims to reduce cognitive rigidity and encourage ‘biggericture’ thinking (Tchanturia et al., 2008).

Exposure interventions should be based on a theoreticalationale that incorporates knowledge of learning, extinctionnd reconsolidation, and which is optimised for neurocognitivendophenotypes found in ED. To tackle cognitive rigidity and dif-culty in integrating and generalising new information, exposurehould be conducted in vivo where possible (as opposed to imaginalr purely in clinic settings), in situations relevant to the individual.ncorporation of naturalistic exposure is routine in the treatmentf anxiety disorders and it is suggested that exposure protocolsor EDs should investigate context manipulation, e.g. some ses-ions towards the end of treatment could be conducted in multipleettings (home, restaurant, supermarket). In the addictions field,ersonal environments (e.g. a favourite pub) rather than standardnvironments (any pub) are more powerful in eliciting craving,nhancing stimulus vividness, relevance, positive affect and excite-ent as well as eliciting greater heart rate changes (Conklin et al.,

010), i.e. personalising exposure makes treatment more effective.uch exposures could be therapist assisted, or self-guided home-ork exercises in the form of behavioural experiments. During

elf-guided exposures, stimuli such as specific items of clothingorn during treatment foods eaten, or cue cards with reminders of

he exposure setting, may function as appropriate retrieval cues.Several methods have been developed to reduce eating related

nxiety during and after food exposure and these may help dis-upt reconsolidation of food-related fear memories. For example,n 64 inpatients with AN, progressive muscle relaxation, guidedmagery or self-directed relaxation were used to reduce post-mealnxiety (Shapiro et al., 2008), and therapeutic ‘vodcasts’, (i.e. audiond visual presentations, aimed at modifying negative reactionso food), played to the individual during mealtimes have beeniloted (Treasure et al., 2010b). By providing competing non-threatemory associations during and after food consumption, these

trategies may be useful additions to exposure therapy protocolsor AN and BN patients (Treasure et al., 2011).

Data from this review also indicate that technologies using vir-ual environments provide alternative ways of delivering exposureherapy that has promising outcomes. The approach is flexible inhat users are able to manipulate a large number of stimuli, and theirtual environment can be structured according to the needs ofndividual patients, whilst monitoring their responses to the virtualcenario (Perpiná et al., 2003; Vincelli et al., 2003). Importantly, itas been suggested that as virtual exposure ED patients are exposedo anxiety provoking cues in a ‘safer’ environment, VRET may beetter tolerated (Perpiná et al., 2003). This approach could also helpvercome context renewal of fear memories, as exposure occurs inustomised situations that enable individuals to better extrapolateearning to their daily lives. Overall, it is possible VRET may be aseful intervention for ED and its implementation is recommendedither as a stand alone treatment or as an intermediary step prioro in vivo exposure.

Exposure therapy in ED may also be augmented with the usef pharmacological agents and/or the addition of a neuromodula-ion component such as rTMS. Further research in these areas isecommended.

Any future research on exposure treatment of ED needs to
nclude multiple outcomes. Thus, alongside self-report and otherxplicit methods of outcome assessment (e.g. reduction in subjec-ive fear and anxiety related to food or urges to eat) the successf exposure treatment should be assessed using implicit methods
such as psychophysiology, eye tracking, startle response or fMRI.Further advances are likely to come from use of animal models ofED to explore cue-induced feeding or feeding inhibition and theirextinction.

5. Summary and conclusions

To our knowledge, this is the first paper in almost two decadesto systematically review the literature on the use of exposuretechniques in people with an ED. Considering the methodologicallimitations, and given what is now known about the mechanismsof extinction and reconsolidation, it is not surprising that earlystudies using exposure techniques (mainly in BN) did not estab-lish if this treatment is a credible alternative to CBT. However,with new knowledge, exposure treatments are beginning to regainpopularity and appear to be a promising area of intervention, partic-ularly in relation to AN where advances in treatment are scarce. Wehave considered developments in contemporary behavioural andneurobiological research into extinction, neuropharmacology, andvirtual technologies and in Box 1 propose several ways in whichthis knowledge might be used to increase the clinical efficacy ofexposure techniques in ED.

We suggest that patients should be adequately prepared priorto engagement in exposure work, and that protocols should beoptimised to incorporate advances in learning theory and themechanisms of extinction and reconsolidation. Pharmacologicalagents are a promising avenue of future research, and should beinvestigated to establish whether they enhance extinction learningin people with ED. In addition, neuromodulation may be a usefuladjunct to exposure treatment. Finally, any future research trialsof exposure therapy for ED should aim for a robust sample size,maximised homogeneity of participants in terms of BMI and othersymptom characteristics, a sufficient duration of exposure, and theprovision of salient extinction memories to prevent reconsolidation
of negative beliefs and inhibit safety behaviours.

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cknowledgements

This paper presents independent research funded by theational Institute for Health Research (NIHR) under its Programmerants for Applied Research Programme (Grant Reference NumberP-PG-0606-1043). The views expressed are those of the authorsnd not necessarily those of the NHS, the NIHR or the Departmentf Health. The work was also supported by the Biomedical Researchentre (BRC) for Mental Health, South London and Maudsley NHSoundation Trust and Institute of Psychiatry, King’s College London.

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