PHB-10901; No of Pages 10

Physiology & Behavior xxx (2015) xxxxxx

Contents lists available at ScienceDirect

Physiology & Behavior

journal homepage: www.elsevier.com/locate/phb

New treatment approaches for severe and enduring eating disorders

Janet Treasure, Valentina Cardi, Jenni Leppanen, Robert Turton
Section of Eating Disorders, Psychological Medicine, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom

H I G H L I G H T S
We describe the development and progression of eating disorders.
Treatment approaches at the different stages of illness are outlined.
Possible change processes and novel treatment approaches are reviewed.

a r t i c l e

i n f o

Article history:
Received 28 February 2015
Received in revised form 22 May 2015
Accepted 4 June 2015
Available online xxxx
Keywords:
Eating disorders
Staging model
Neuroprogressive changes
Treatment targets
Novel interventions

a b s t r a c t
Objective: The aim of this paper is to map the possibility of new treatment approaches for eating disorders.
Background: Eating disorders have a protracted trajectory with over 50% of cases developing a severe and enduring stage of illness. Although a good response to family-based interventions occurs in the early phase, once the
illness has become severe and enduring there is less of a response to any form of treatment. Neuroprogressive
changes brought about by poor nutrition and abnormal eating patterns contribute to this loss of treatment
responsivity.
Method: We have summarised the prole of symptoms at the various stages of illness and considered new treatments that might be applied.
Results: In the enduring stage of illness in addition to problems with body image, food and eating, there are additional problems of low mood, high anxiety and compulsivity and problems in social functioning. This suggests
that there are dysfunctions in circuits subsuming reward, punishment, decision-making and social processes.
New approaches have been developed targeting these areas.
Conclusion: New interventions targeting both the primary and secondary symptoms seen in the enduring stage of
eating disorders may improve the response to treatment.
2015 Elsevier Inc. All rights reserved.

1. The prevalence and characteristics of eating disorders

Eating disorders have been described as being amongst the most difcult psychiatric conditions to treat [40,64]. It has been found that up to
0.3% of young women might develop Anorexia Nervosa (AN) and 1% Bulimia Nervosa (BN) across the lifespan [71]. For males a similar trend is
reported although prevalence rates are lower than for females [147].
The Diagnostic and Statistical Manual of Mental Disordersfth edition
(DSM-5; [6]) criteria for AN include signicant weight loss (i.e., relative
to an individual's sex, age and developmental trajectory) and an acute
sense of fear associated with increasing weight. The criteria for BN are
the presentation of binge eating (i.e., eating large amounts of food during a two-hour period associated with a sense of loss of control) and

Corresponding author at: Section of Eating Disorders, King's College London, Institute
of Psychiatry, Psychology and Neuroscience, 103 Denmark Hill, London SE5 8AF, United
Kingdom.
E-mail addresses: janet.treasure@kcl.ac.uk (J. Treasure), valentina.cardi@kcl.ac.uk
(V. Cardi), jenni.leppanen@kcl.ac.uk (J. Leppanen), robert.turton@kcl.ac.uk (R. Turton).

compensatory behaviours such as self-induced vomiting and laxative

abuse. A transdiagnostic concept across both illnesses is the overevaluation of shape and weight (i.e., extreme importance is given to
shape and weight in dening the self). For many sufferers of eating disorders these life-threatening conditions run a protracted course;
resulting in a profound impact upon an individual's health and psychosocial functioning.
2. A staging model of eating disorders
A unique longitudinal study from Sweden described the long-term
trajectory of a cohort of AN cases ascertained early in the course of
their illness (aged 15) [165]. The cohort was assessed at 16, 21, 24 and
32 years of age and compared to a group of healthy controls on a global
assessment of functioning and the MorganRussell Outcome Assessment Schedule [114]. The mean duration of illness was found to be
over 7 years for eating disorder psychopathology. The group with
premorbid obsessivecompulsive personality disorder and autistic
spectrum traits had a longer course [8,165]. Only one patient did not

http://dx.doi.org/10.1016/j.physbeh.2015.06.007
0031-9384/ 2015 Elsevier Inc. All rights reserved.

Please cite this article as: J. Treasure, et al., New treatment approaches for severe and enduring eating disorders, Physiol Behav (2015), http://dx.
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meet the criteria for an affective disorder (i.e., depression) within the
18-year follow-up period (i.e., by 32 years of age). Thus, anhedonia, anxiety and autistic and obsessivecompulsive spectrum traits are features
of late stage AN. This complexity may contribute to the loss of treatment
responsivity in people with the severe and enduring form of illness.
A recent retrospective cohort study found that over 50% of eating
disorder cases develop a severe and enduring illness [145]. Gender comparisons revealed a 39% remission rate for females versus 59% for males
after ve years of illness duration. Moderating factors for the outcome of
AN include illness duration, age of onset and presence of co-morbidities
[143]. Based upon this evidence, a staging model of eating disorders has
recently been formulated [156]. This framework incorporates the concept of a form of neuroprogression developing over time associated
with the need to match treatment to the stage of illness.
The staging model maps eating disorder psychopathology to the following stages: high risk, prodromal, full syndrome and severe and enduring. During childhood and adolescence individuals may become
predisposed towards the development of an eating disorder due to the
presence of high-risk markers. Shyness, social problems and obsessivecompulsive personality traits [8,54,165] seem to predate the
onset of AN whereas, the traits that precede BN include a tendency to
overeat [136] and problems with attention and impulsivity that may
manifest as Attention Decit Hyperactivity Disorder (ADHD) traits in
childhood [111,132]. A signicant amount of evidence has been found
suggesting that childhood anxiety is also a high-risk marker for AN
and BN [55,78].
These vulnerability factors can lead to a prodromal phase
characterised by sub-clinical symptoms. During this early stage of illness symptoms can occasionally improve without engagement with
clinical services and increased rates of diagnostic cross-over occur
[156]. If prodromal symptoms do not remit, during early adulthood
they may transition into the development of a full-blown eating disorder. For AN, the time frame for this early stage of illness is currently
outlined as being lower than three years in duration. In regard to BN,
currently there is insufcient evidence to dene time frames for the
different stages of illness [156].
The nal stage outlined by the model is the severe and enduring
stage of illness, which may be dened as a prolonged illness of over
seven years in duration [156]. It is hypothesised that neuroprogressive
changes brought about by poor nutrition and/or abnormal eating patterns and diminished psychosocial resources lead to the complex prole
of morbidity characteristic of this later stage. For instance, evidence has
been found that in the severe and enduring stage of AN brain size is reduced particularly in the cerebellum and mesencephalon [46]. The atypical brain activation to illness relevant cues (for example salient body
shape images) is more pronounced in adults than adolescents [43,44].
3. The eating disorder phenotype

stimuli. This has led to suggestions that an impulsive/compulsive

endophenotype might underlie the habitual nature of binge eating
in BN [125,135].

3.2. Social difculties

Individuals with eating disorders experience pervasive interpersonal difculties, some of which predate illness onset and are associated
with a poor outcome [8,165]. It has been suggested that abnormal eating
behaviours might serve as a strategy to improve social acceptance [124,
155]. Problems in many aspects of social cognition were seen in a systematic review and meta-analysis of the literature [20]. A habitual tendency to interpret interpersonal encounters in a negative way might
contribute to the maintenance of poor social adjustment, and in turn reinforce abnormal eating behaviours. Studies conducted by our group illustrate that patients have an attentional bias towards threatening faces,
rather than neutral or compassionate expressions [21,22] and tend to
interpret ambiguous social scenarios more negatively than healthy subjects [176]. Vigilance to social threat is attenuated in subjects who recovered from the illness [21], suggesting that it might be related to the
secondary consequences of starvation. Neuroprogressive changes associated with dietary restriction, bingeing and purging may accentuate
the impaired ability to relate to others.

3.3. Emotional difculties

Negative emotional states also contribute to the maintenance of eating disorders. Studies employing daily assessments in naturalistic settings (i.e. ecological momentary assessments) indicate that negative
emotional states are associated with binge episodes in patients with
BN and Binge Eating Disorder (BED) [59,62] and with dietary restriction
in patients with AN [38,94]. Laboratory-based studies have provided evidence for the impact of negative affective states such as anxiety on caloric intake (higher anxiety, lower intake; [142] and eating-disorders
symptoms, such as feelings of fatness and urge to restrict [167] in AN. Interestingly, a recent study investigating the effects of eating on mood
found that both patients with BN and AN reported increased negative
affect during meal consumption [10]. In a recent meta-analysis conducted by our group we found that positive mood induction is positively
associated with increased food intake on a test meal in patients with AN
[176]. A decrease in food consumption was found for patients with BN.
These ndings suggest that the use of strategies to disrupt the learned
association between eating and negative emotions might help patients
to develop a more positive attitude towards food and eating. This appears important as a recent systematic review of the literature found
that although anxiety levels might decrease following treatment for
AN they still remain above non-clinical norms [85].

The eating disorder phenotype is characterised by difculties experienced in a range of different domains.
3.4. Neural substrates of cognitive, social and emotional difculties
3.1. Cognitive difculties
Clinically, individuals with AN present with rigid thoughts and behaviours relating to eating and weight. Inexibility and poor central coherence have been found in patients with AN [91,92,126,138]. These
difculties are particularly strong in those with comorbid obsessive
compulsive disorder, obsessivecompulsive personality disorder or autistic traits. These traits have been associated with a poor response to
treatment [4,8,30,166] and may underpin the compulsive nature of AN
[56].
In contrast to over control in AN, impairments in inhibitory control have been found in a systematic review of BN [171]. These decits were found to be particularly strong for disease-salient stimuli
including highly palatable foods, eating, and body weight related

Problems in the neural circuits of the limbic system are thought to

explain some of the cognitive, social and emotional abnormalities
found in eating disorders [52,79,97]. The circuits involved in these behaviours include frontal regions (medial prefrontal cortex, lateral
prefrontal cortex and orbitofrontal cortex), the striatum (caudate and
striatum) and the nucleus accumbens [177] and the insula [118]. The
evidence points to a hyper-responsive cortico-limbic-striatal circuit in
response to food but in contrast, a hypo-responsive fear network in
response to standard fear eliciting stimuli [174]. Decreased dopaminergic neurotransmission has been found in the mesolimbic reward
system in recovered patients which supports general avoidance motivation, difculties in cognitive exibility and anhedonia in AN [47,
48].

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4. Maintenance models of the phenotype

4.1. Clinical maintenance models of AN
The maintenance of AN leading to an enduring form of illness has
been described. The cognitive interpersonal model of Schmidt and Treasure [131] describes how the visible aspects of AN which are relevant for
interpersonal processes add to the valued elements, such as feelings of
control and adherence to rules and channelling negative emotions and
lack of connection to others into food as a form of emotional regulation
[131,155]. These behaviours, repeated over time, become ingrained
habits [56,163].
These habits resemble those found in Obsessive Compulsive Disorders, rather than in BN, in that they are formed from avoidant rather
than appetitive goals [53,125]. Interventions to break these unhelpful
habits might be of benet in AN.
4.2. Clinical maintenance models of loss of control over eating
Abnormalities in the reward system might account for some of features of the binge eating phenotype. In BN there appears to be decreased
responsiveness of the reward system, especially to taste reward. There
are two possibilities that may account for this. First, the reward deciency may be an innate vulnerability. He et al. [69] found that in
healthy subjects difculties inhibiting the response to high calorie
food cues on the Go/No Go task were associated with increased activation to these stimuli in the right striatum (a circuit involved in habits).
These ndings were stronger for participants with a higher body mass
index. Houben [72] found that participants with difculties in inhibitory
control consumed greater amounts of highly palatable food on a test
meal than participants with strong inhibitory control. These difculties
in inhibition may make individuals more prone to indulge in highly palatable food due to the strong impulses they elicit [72]. The secondary
consequences of impulsive/compulsive, over control and loss of control
over eating seen in BN and BED may then lead to neuroadaptive changes
in which a habitual addictive type response to food develops.
The second possible explanation for the abnormalities in reward
sensitivity is that the reward system may be downregulated as a
neuroadaptive process to the over/under eating cycles. This latter mechanism may be relevant in obesity as adolescents at high risk for future
obesity have a hyper-responsive reward system [144]. Patients with
BN also exhibit impaired brain activation in the inhibitory control network (fronto-striatal loops including the lateral prefrontal cortex,
precentral cortex, anterior cingulate cortex, and putamen [99,104,
105]). Interventions to increase inhibitory control and/or to moderate
the hedonic aspects of eating may be of value.
5. Treatment approaches at the different stages of illness
There is a paucity of evidence from high quality trials to answer
questions in the enduring stage of illness about which treatments are
acceptable and how much benet accrues. Much more is known about
the earlier stages of illness as can be seen in recent guidelines
(e.g., [66]). In the very early prodromal stage dissonance-induction
techniques and body acceptance interventions can prevent symptom
progression [178]. In the early stage of AN family-based therapies are
helpful [42,66].
Regarding the treatment of BN, guidelines have recommended that
Cognitive Behavioural Therapy (CBT), possibly in a self-help format,
should be the rst line of therapy [66]. The failure of an early response
within the rst 4 weeks may signal the need to switch to other forms
of treatment. Support for the use of specialist individual therapies,
such as an enhanced version of CBT [16,39] and interpersonal psychotherapy, has been found for patients with BN [12,26].
Once the illness has become severe and enduring there is less of a response to any form of treatment and there is uncertainty about clinical

management [67,168]. Currently, there is no recommended rst-line

therapy for adults presenting with AN in the later stages of illness
[66]. The limited evidence available for patients in the severe, enduring
stage of illness suggests that remission rates are modest and treatment
acceptability is poor [66]. Treatment drop-out can be high from outpatient treatment [33] and 2641% of patients need additional in- or
day-patient care, because of either a failure-to-improve or a deterioration of symptoms [40,175]. A focus on more of the psychosocial consequences of the illness may be of benet for this stage delivered either
individually [153] or through the family [179]. Further exploration of
treatment approaches for people who do not respond or who do not receive a timely rst line effective intervention is needed.
Many treatments for eating disorders have been adapted from
those used to treat other conditions. It is possible that a more
targeted approach to key eating disorder symptoms may improve
outcomes. Translating from experimental medicine into clinical
practice involves a variety of steps. The rst is to build an accurate
clinical prole of the various symptoms and model the underpinning
psychopathology. The next stage is to consider possible techniques
to foster change and to modify these dysfunctional systems. If we
apply this construct to eating disorders then we are probably at the
drawing board stage of model building especially for those in the
severe enduring phase of illness.
6. The use of novel interventions to change the factors that maintain
the illness
The symptoms described above include several areas that can be
targeted with new treatments. The new understanding about brain
plasticity has led to the development of a wide variety of interventions
that guide this malleable potential of the brain through training, drugs,
transcranial magnetic stimulation and neurosurgical methods. These
novel treatment approaches may be useful as adjunctive strategies to
help improve the treatment outcomes for patients with severe and enduring eating disorders.
Childhood anxiety, increased sensitivity to punishment, obsessive
compulsive and autistic traits and increased sensitivity to fear learning
are some of the vulnerability factors which predispose to the onset of
AN (see Fig. 1). Once the illness develops, core symptoms, such as restriction, weight loss and weight-, shape- and food-related preoccupations appear. With the illness progression, neuroprogressive
secondary changes such as rigid eating habits; cognitive emotional
and social difculties and abnormalities in brain structure and function
develop and in turn reinforce the illness. It is suggested that new treatment approaches could be used to target the neuroprogressive changes
which occur in AN.
Abnormalities in appetite regulation, childhood anxiety, reward sensitivity and inhibitory control are some of the vulnerability factors that
predispose the onset of BN (see Fig. 2). Once the illness develops, core
symptoms, such as cycles of restriction and loss of control over eating
and weight-, shape- and food-related preoccupations appear. With illness progression, neuroprogressive secondary changes such as rigid
eating habits and addictive-like changes; cognitive emotional and social
difculties and abnormalities in brain structure and function develop
and in turn reinforce the illness. It is suggested that new treatment approaches could be used to target the neuroprogressive changes that
occur in BN.
6.1. Targeting cognitive functioning
Cognitive Remediation Therapy (CRT) is a novel form of therapy that
has been adapted for patients with eating disorders [150] from its initial
use for other disorders such as brain injury [27] and schizophrenia
[169]. The approach can be delivered as an individual [32], group
[180] and more recently family-based approach [74]. During CRT sessions patients are engaged in fun and playful activities aimed at

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Fig. 1. A model to describe the development of severe and enduring AN and new treatment approaches.

improving neurocognitive decits in set shifting (thinking more exibly) and central coherence (seeing the bigger picture as opposed to focusing on the details) and the enhancement of meta-cognitive skills
[148]. Thus, CRT targets cognitive styles that are associated with obsessivecompulsive personality traits that are associated with a poor prognosis in AN [126].
Case studies and pilot studies have demonstrated that CRT is a feasible and acceptable form of treatment for adults [151] and children and
adolescents [31] with AN. Studies have demonstrated that CRT can be
helpful for patients with AN in reducing cognitive rigidity [149], developing more global processing styles [45] and improving visualspatial
memory [31]. Randomised controlled trials have provided further evidence that CRT seems to be benecial in lowering dropout rates from
outpatient treatment [98], increasing patients' set-shifting abilities
[19] and elevating patients' quality of life [34].
Although these ndings are very promising, research in this area has
predominantly focused on AN. Preliminary ndings have indicated that
CRT may be useful as a treatment enhancer for weight disorders such as
obesity [122]. Therefore, adapting CRT further for other clinical populations such as patients with BN and BED appears a potential future direction for CRT [18] Further research to examine the stage of treatment that
CRT is most effectively delivered (i.e., prevention, early-stage, severe
and enduring, relapse prevention) would be of benet.
6.2. Targeting emotional difculties
In preliminary experimental medicine studies we have investigated
the use of short video-clips including relaxing background music, pleasant images, and scripts to induce positive mood and motivation for recovery in patients with AN [24,25]. The development of these multi-

component video-clips is based on several theoretical frameworks.

Namely, a number of authors have discussed the use of music therapy
to positively affect physiological functioning [70,89]. Imagery has been
proposed as a useful means to elicit specic cognitions, affects and behaviours related to food and it has been shown to modify behavioural
eating patterns [77]. Finally, inducing positive emotions can restore
self-regulation [152] and psychological and physical wellbeing [49,50].
Our recent ndings in patients with AN indicate that the use of these
video-clips is associated with increased calorie consumption during a
test meal, reduced anxiety and higher levels of positive mood compared
to a music only, control condition [23]. For patients with BN, the mood
induction strategy was associated with a large reduction in their level
of vigilance towards food stimuli [23]. These promising ndings suggest
that this approach may be benecial as a strategy to help improve mealtimes on inpatient units. Further research may seek to examine whether
personally tailored video scripts lead to enhanced treatment effects.
6.3. Targeting social difculties
In recent years, Cognitive Bias Modication (CBM) procedures have
been developed with the purpose of modifying negative cognitive
biases in interpretations and attention in a range of clinical populations
including: affective disorders [68,181], obsessivecompulsive disorder
[29] and substance abuse [133]. There are two main variants of CBM
procedures, both of which are computerised [101]. One approach is
targeted at changing negative biases in attention through the use of a
modied visual version of the dot-probe task [102]. In this paradigm
two stimuli appear onscreen; one of which is positively valenced and
the other negatively. A probe then appears onscreen for a very brief
period of time and patients must react to it as quickly as possible by

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Fig. 2. A model to describe the development of severe and enduring BN and new treatment approaches.

pressing a computer key. In order to direct attention away from the

negative stimulus and towards the positive, this probe is repeatedly
presented onscreen in the space where the positive stimulus was
positioned. The second CBM approach helps to remediate negative
biases in interpretation. This approach involves patients listening via
headphones to ambiguous scenarios that have the risk for a negative
interpretation (e.g., you haven't spoken to a close friend in a while so
you message them to see how they have been. It's been several hours
since you messaged them but they haven't replied) but are given a
positive resolution.
Quantitative data indicate that CBM can remediate negative attention and interpretation biases towards emotionally relevant stimuli
(e.g. facial expressions; emotionally valenced words) or anxiety- and
depression-specic stimuli with a moderate sized effect in clinical and
sub-clinical populations (g = 0.49; [63]. This effect was found to be
greater for remediating negative biases in interpretation (g = 0.81)
than in attention (g = 0.29). Also, a recent meta-analysis found that benign interpretation training was associated with a signicant increase in
positive interpretation and decrease in negative mood in healthy controls, subclinical and clinical populations [110].
In a proof of concept study, a CBM intervention targeting negative
self-beliefs was associated with a reduction in eating disorder symptoms in a subclinical sample [172]. Furthermore, a recent study from
our group tested the use of 5 sessions of combined attentional and interpretation bias training in a sample of 28 inpatients with severe and
enduring AN. Findings indicated that at the end of intervention participants showed a medium sized increase in attention to smiling faces and
fewer negative interpretations of ambiguous social stimuli. Also, there
was an increase in self-compassion and self-reported symptoms of anxiety [176]. These preliminary ndings suggest that CBM might have a

potential in targeting negative information processing in eating disorders. It remains to be tested whether such an approach modies core
symptoms such as eating behaviour.

6.4. Targeting eating behaviour habits and underlying processes

6.4.1. Implementation intentions
This goal-based approach to changing habits involves the planning
of when and how an individual will perform the desired behaviour
through an IF-THEN format. For instance, if I feel like buying my
binge foods from my local store, then I will try going to a different supermarket. This strategy to change behaviour has been tested as an approach to help individuals develop healthier eating patterns [3].
Clinically, implementation intentions have primarily been tested as
a strategy to help develop healthier eating patterns and aid weightloss in obesity. Teaching overweight women how to form implementation intentions results in higher levels of weight-loss [100]. Furthermore, this approach has also been reported to increase adherence to
meal-replacement programmes in overweight individuals leading to
signicant reductions in participants' BMI [173]. To date, no studies
have examined the use of implementation intentions in AN or BN.
They might be useful in the treatment of eating disorders when used
alongside the use of self-monitoring techniques such as thought/food
diaries that are often used as part of CBT interventions for eating disorders [116]. This may allow for the specic targeting of IF-THEN plans to
eating disorder habits [93].
Troop [157] found that the effect of the formation of implementation
intentions to increase greater fruit and vegetable consumption was
moderated by participants' level of dietary restraint. It is therefore

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uncertain whether this approach can be applied to AN where levels of

restraint are extreme.
6.4.2. Exposure therapy
Exposure therapy is based on the deliberate and planned systematic
exposure to a feared stimulus, or representation of the stimulus, in a safe
environment [123]. The aim is to confront (rather than avoid) the stimulus in order to: 1) learn that it does not signal danger; and 2) develop
effective strategies of coping with the anxiety [123]. The approach has
been found to be an effective treatment for a range of affective disorders
that are often co-morbid with eating disorders such as social phobia [65]
and obsessivecompulsive disorder [2]. Recent evidence-based theoretical models of AN conrm the pivotal role played by food-related anxiety in the onset and maintenance of the illness [137,141,146,154].
Therefore, researchers have suggested that exposure-based therapies
maybe a useful adjunctive treatment for patients with AN [139,140].
A recent review highlighted the potential of in vivo gradual exposure
to food stimuli to reduce food-related anxiety and increase caloric intake in AN [88]. However, previous research has not been conducted
in patients in the severe and enduring stage of AN. We recently found
that eight sessions of gradual and guided exposure to food stimuli can
be helpful in reducing anxiety levels and eating-related fears in patients
with a severe and enduring illness [176]. An examination of neural specic symptom changes showed that activity in the cingulate-frontoparietal network was found to be signicantly lower in response to
food stimuli post-treatment.

healthy or unhealthy snack following the task or if their desire to eat

was extinguished. The mobile-application was found to signicantly reduce participants' snacking of unhealthy food items over a one-week
period. Qualitative data suggested that participants reported that the intervention helped to increase their mood and their level of self-control
over snacking behaviour [73].
Currently, there has been a limited amount of research examining
the clinical application of approaches to disrupt craving imagery. To
our knowledge, the only study to date [82] found that for overweight
women on a prescribed weight-loss diet an imagery-based intervention
was signicantly more effective in lowering food cravings relative to
thought-suppression. However, this study did not examine the impact
of the intervention on actual food intake. Further proof of concept research is needed to establish whether disrupt craving imagery approaches are helpful for clinical populations.
7. The use of brain stimulation (external and internal) to change the
factors that maintain the illness
Neuromodulation in the forms of Deep Brain Stimulation (DBS), repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS) has emerged as a non-destructive,
adjustable and largely reversible means of altering brain circuitry. The
circuits involved in reward, mood regulation and inhibition have been
the targets of neuromodulation approaches for eating disorders.
7.1. Deep brain stimulation

6.4.3. Inhibition training

Targeting impulsive actions such as loss of control over eating
through strengthening inhibitory processes through training is potentially another valuable technique. This may be a benecial treatment
for patients with BN to help increase inhibitory control over the highly
palatable foods (e.g., deserts and snacks) that are typically consumed
during binge episodes [127]. The go/no go paradigm has been developed as a novel computerised approach to help train individuals to inhibit their automatic impulses towards highly palatable foods. This
technique involves the presentation of food stimuli onscreen that are
paired onscreen with a go/no go cue (e.g., an arrow pointing left or
right). No go cues are consistently matched with pictures of highly palatable food and go cues linked with healthier food choices. Participants
are informed that they must withhold their response when a no go cue
is presented and to respond accurately meaning that the task uses a
choice reaction time method to train participants to increase their inhibitory control over highly palatable binge foods [182].
Stop-Signal Training is a novel variant of the go/no go approach that
involves a variable delay between the presentation of the food stimulus
onscreen and the presentation of the stop-signal. This training approach
requires the inhibition of an already initiated motor response [171]. Research has suggested that both of these approaches appear to be promising methods to help reduce the consumption of highly palatable foods
[95,161]. These approaches have been found to be effective in chronic
dieters [160] and in healthy participants with low levels of inhibitory
control [72]. Further research with clinical samples appears warranted
due to the potential for these approaches to help patients that habitually
overeat.
6.4.4. Craving imagery disruptions
Food craving has been identied as a precursor to binge eating in
obese individuals [60,130] and in patients with BN [112,164]. Proof of
concept studies have investigated whether imagery can disrupt food
cravings [81,134]. The strength and frequency of cravings can be reduced [11], which has been found to lower craving-driven food consumption [83]. Recently, Hsu et al. [73] tested the effectiveness of a
mobile-based application called iCrave, which prompts participants to
complete a 10 second visualisation task when experiencing a food craving. Participants are then asked to record whether they consumed a

This neurosurgical technique uses electrical impulses to target dysfunctional brain circuits through the implantation of a brain pacemaker
into the cortex. The procedure has been used across a range of disorders
including treatment resistant depression [128,129], refractory obsessivecompulsive disorder [1], Parkinson's disease [15] and Tourette's
syndrome [162]. This procedure is nonlesional and has been reported
to be a safe treatment in both the short and long-term in the treatment
of movement disorders [84]. It has been suggested that this approach
may be a viable treatment option for patients in the severe and enduring
stage of illness as a method to target the neurobiological mechanisms
that underlie symptoms [119,120].
A preliminary study from China with DBS of the nucleus accumbens
in the early stage of AN reported benets [170]. DBS in the subcallosal
cingulate (an area implicated in treatment resistant depression) has
also been used. A case report described DBS applied to this region as
treatment for depression was found to also improve ED symptoms
[75]. A recent prospective phase 1 trial from Canada noted that three
of the six patients with severe enduring illness treated with DBS to the
subcallosal cingulate region improved their physical status, matched
with improvements in quality of life, at 9 months. Furthermore, there
was improved mood, anxiety, affective regulation, and AN-related obsessions and compulsions in four patients and the harms (a t (one
case) and post-operative bleeding (one case) were not excessive [96].
Larger studies of DBS in patients with AN are required to clearly dene
the role of DBS for patients that have a severe and enduring illness.
7.2. Repetitive transcranial magnetic stimulation
Barker, Jalinous and Freeston [13] rst described the therapeutic approach of rTMS which involves the magnetic stimulation of the cerebral
cortex via the generation of an electromagnetic eld from a coil. Research with animals has found that rTMS can be effective in increasing
feeding behaviours [57], modulating serotonergic activity [183] and increasing brain derived neurotrophic factor [115]. Consequently, rTMS
may represent a novel therapeutic approach for eating disorders due
to its potential for changing eating behaviour and its regulation [158].
Case studies have demonstrated that 20 sessions of rTMS targeted at
the Dorsolateral Prefrontal Cortex (DLPFC) can lead to improvements in

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J. Treasure et al. / Physiology & Behavior xxx (2015) xxxxxx

eating disorder symptomatology and mood in patients with severe and

enduring AN [76,109]. Promising ndings have also been found when
targeting the DMPFC in patients with treatment resistant BN [37]. In a
recent pilot study including ten patients with AN, Van den Eynde et al.
[159] found that one session of rTMS targeted at the left DLPFC reduced
feelings of being fat, full and anxiousness. Further research is needed to
clarify the optimal parameters of rTMS for the treatment of eating
disorders.
7.3. Transcranial direct current stimulation
tDCS modulates neural excitability via the application of a low current to a targeted area of the cortex through the placement of electrodes
onto the scalp [117]. Food cravings have been found to be reduced by
tDCS targeted at the prefrontal cortex [51,58,108]. Kekic et al. [80]
found that a 20-minute session of tDCS directed at the DLPFC led to temporary reductions in cravings for sweet rather than savoury foods. They
also found that this effect was strongest for participants who were less
impulsive on a temporal discounting task. Therefore, it may be benecial to combine treatment approaches such as tDCS with inhibition
training approaches to help reduce cravings [5].
These positive results suggest that tDCS could be benecial for clinical populations. Montenegro et al. [113] found that tDCS targeted at the
DLPFC relative to a sham condition can lead to reductions in obese individuals' desire to eat when combined with aerobic exercise. Research in
clinical populations with BN and BED is lacking [108]. Altogether, the
application of tDCS as a clinical intervention is in its infancy [5]. To indicate its efcacy as a clinical treatment research with larger sample sizes
from multiple sites may be helpful using a multi-modal assessment of
outcomes rather than just visual analogue scales to assess cravings [90].
8. The use of pharmacology to target the factors that maintain
the illness
8.1. Oxytocin
The role of oxytocin, a hormone, in social processes, such as parental
ponding has been well established in animal research (e.g. [106]). Recently there has been increasing interest in investigating oxytocin as a
potential treatment enhancer in autism, schizophrenia and anxiety disorders [7,41,61,121]. Results so far have indicated that oxytocin may be
benecial in promoting trust, improving identication of social emotional communication and attenuating negative interpretation bias [9,
14,35]. As autistic traits have been found to be a prognostic factor for
the outcome of eating disorders [165] and the inclusion of interpersonal
difculties in numerous maintenance models of eating disorders
e.g., [39,155] it appears warranted to examine the use of oxytocin as a
treatment enhancer [103].
Proof of concept studies in AN have been undertaken with oxytocin
by examining the impact of single dose intranasal administration of
oxytocin. These studies found that the attentional bias towards food
and body image stimuli was reduced [86] as was the attentional bias towards negative facial emotions (disgust, anger) [87]. These nding suggest that oxytocin might moderate some of the fear processing and
avoidance associated with the maintenance of AN.
8.2. Lisdexamfetamine dimesylate (Vyvanse)
Vyvanse is an amphetamine that works through stimulating the central nervous system. The drug has been used as a treatment for ADHD
[17,36] and has recently been approved as a medication for the treatment of moderate to severe BED by the Food and Drug Administration
(FDA) in the United States. It is hypothesised that the drug might help
to regulate dysfunctional dopamine systems [107]. A recent systematic
review of the literature found that over an 11 week trial a 50 or
70 mg/day dosage of Vyvanse is effective in reducing binge eating

episodes for moderate to severe patients relative to a placebo [28]. However, this review highlighted that a long-term analysis of the treatment
efcacy and safety prole of the drug is needed. This appears necessary
due to the potential risk of severe adverse effects associated with amphetamines and the potential for drug dependence/abuse.
9. Conclusion
In line with a consideration of the staging categorisation of people
with eating disorders it might seem necessary to develop a form of
stepped care protocol for patients with eating disorders. In the case of
people who are resistant to standard rst line therapy it may be benecial to use treatments that directly target some of the dysregulated circuits that maintain the disorder. These may circumvent the need to
work only through top down processes, which are disabled by the
neuroprogressive changes that ingrain in the habits and fears that maintain the disorder. This is an area of rapid growth that may offer hope to
people at the severe enduing stage of the disorder.
Acknowledgements
This study was part funded by the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at the South
London and Maudsley NHS Foundation Trust and King's College
London. Valentina Cardi is funded by the National Institute for Health
Research (NIHR)'s Research for Patient Benet Programme (Grant Reference Number RP-PG-0712-28041). Jenni Leppanen and Robert Turton
receive studentships funded by the Psychiatry Research Trust (PRT) and
by the Institute of Psychiatry, Psychology & Neuroscience (IOPPN)/Medical Research Council (MRC) (Grant Reference Number 29 Treasure).
The views expressed are those of the author(s) and not necessarily
those of the NHS, the NIHR, IOPPN, MRC, PRT or the Department of
Health.
Potential conict of interest: The author(s) declare having no conict of interests in the writing of this paper.
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