Physiology & Behavior 118 (2013) 63–69

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Physiology & Behavior

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

‘Food addiction’ and its association with a dopaminergic multilocus

genetic profile
Caroline Davis a, c,⁎, Natalie J. Loxton b, Robert D. Levitan c, Allan S. Kaplan c,
Jacqueline C. Carter d, James L. Kennedy c
a
School of Kinesiology and Health Sciences, York University, Toronto, Canada
b
School of Psychology, The University of Queensland, Brisbane, Australia
c
The Centre for Addiction and Mental Health, Toronto, Canada
d
Memorial University, St Johns, Newfoundland and Labrador, Canada

H I G H L I G H T S

• Food addiction (FA) is associate with enhanced dopamine signaling.

• Overeating facilitates relationship between FA and dopamine genetic markers.
• FA appears to be a reward-responsive phenotype of obesity.

a r t i c l e i n f o a b s t r a c t

Article history: Background: Our objective was to employ a novel genetic methodology – whereby functional variants of the do-
Received 1 December 2012 pamine pathway were aggregated to reflect a polygenic liability – in the study of food addiction. We anticipated
Received in revised form 4 April 2013 that the composite index of elevated dopamine signaling (a multilocus genetic profile score [MLGP]) would dis-
Accepted 6 May 2013 tinguish those with a designation of food addiction (according to the Yale Food Addiction Scale [YFAS] criteria),
and age and weight equivalent controls. Our second aim was to assess whether this index was positively associ-
Keywords:
ated with eating-related sub-phenotypes of food addiction (e.g. binge eating and food cravings).
Food addiction
Dopamine
Methods: Adults (n = 120) recruited from the community were solicited for an overeating/overweight study.
Genetics Eating-behavior questionnaires were completed and a blood sample was taken for genotyping.
Mediation Results and conclusions: The YFAS identified 21 participants with food addiction. As predicted, the MLGP
score was higher in those with YFAS-diagnosed food addiction, and it correlated positively with binge eating,
food cravings, and emotional overeating. We then tested a multiple-mediation model proposing that reward-
driven overeating facilitates the relationship between the MLGP score and food addiction. The model was
statistically significant, supporting the view that the relationship between a composite genetic index of
dopamine signaling and food addiction is mediated by certain aspects of reward-responsive overeating.
© 2013 Elsevier Inc. All rights reserved.

1. Introduction
While “behavioral addictions” have been recognized by scientists
and clinicians for many years [1], they have only recently been en-
dorsed by the American Psychiatric Association with the proposed
classification of Addiction and Related Disorders in the new Diagnos-
tic and Statistical Manual [DSM]-5 [2]. The DSM diagnostic shift is
timely in light of growing evidence that excessive consumption of
hyper-palatable food is an identifiable clinical entity with striking
biobehavioral parallels to drug abuse [3–5]. Unfortunately, some dis-
cussions on this topic conflate obesity and overeating with ‘food
⁎ Corresponding author at: York University, 343 Bethune College, 4700 Keele Street,
Toronto, ON M3J1P3, Canada. Tel.: +1 416 736 2100x77327.
E-mail address: cdavis@yorku.ca (C. Davis).
addiction’, which tends to cloud its distinctiveness and muddle vali-
dation efforts.
Research has shown clearly that repeated consumption of high
sugar/fat food can produce dopamine signaling changes in the brain
which result in abnormally sustained stimulation of the reward system
[6]. As we have seen from preclinical studies [7], over time, and when
combined with intermittent periods of food restriction, a sugar-
enhanced diet can lead to the same excessive pattern of intake, and
the same behavioral symptoms, observable when animals are exposed
to addictive drugs like heroin. A recent case–control study has also pro-
vided good human evidence that food addiction is a distinguishable
syndrome with psychiatric co-morbidities and a psycho-behavioral
profile remarkably similar to conventional drug-abuse disorders [8].
For example, two studies have shown that about half the obese adults
who met criteria for food addiction according to the Yale Food Addiction

0031-9384/$ – see front matter © 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.physbeh.2013.05.014
64 C. Davis et al. / Physiology & Behavior 118 (2013) 63–69
Scale (YFAS) [9] were co-morbid for binge eating disorder (BED) [8,10].
While there has been little study of the neurobiological similarities
between YFAS-diagnosed food addiction and other drug-addiction dis-
orders, supporting evidence can be found in related functional neuro-
imaging research. For instance, very tasty and attractive-looking food
has shown reinforcing characteristics in the brain similar to those
found from drugs of abuse, and the same brain changes reported for he-
donic overeating are also seen in various types of addictions [11–13].
1.1. Vulnerability to addiction
One of the striking features of addiction is that most individuals
who take psychoactive substances do not develop dependence. This
recognition has prompted efforts to identify a vulnerable phenotype
whose predisposing traits determine the neuroplasticity induced by
addictive behaviors [14]. Addiction is a dynamic and multistage pro-
cess. Indeed, the transition from casual drug use to dependence has
been described as a shift to the “dark side” — that is, from initial plea-
sure, to a need for the behavior to relieve the anhedonia that ensues
from abstinence [15]. Therefore, it is highly unlikely that a homoge-
neous set of risk factors pertains to all phases of its development.
Variation in the sensitivity of brain reward circuitry has been the
focus of many vulnerability studies. Some research indicates that
a high responsiveness to the prospect or delivery of reward is a
high-risk endophenotype for addiction because these individuals are
novelty seekers and easily pleased by rewarding stimuli in their envi-
ronment [16]. Other evidence supports the opposite view — that
natural rewards inadequately activate hedonic tone in certain indi-
viduals because brain reward circuitry has diminished signaling
strength [17]. It is further argued that since potent pharmacologic re-
wards provide a pleasing dopamine ‘boost’, the tendency to use these
behaviors is increased. Efforts to reconcile the two perspectives have
proposed that high reward sensitivity may be a risk during the initia-
tion and escalation stages of addiction, but that the consequent
dopamine-system down-regulation contributes to its maintenance
and the proneness to relapse [15,18].
Neuroimaging studies, which simply illustrate the current state of
brain-circuitry activation, have mostly used case–control designs in
addiction-risk research, constraining the ability to separate causal
traits from consequences of the behavior [16]. Self-report measures
of reward sensitivity are also limited by the incapacity to distinguish
antecedents from outcomes in those with addiction disorders. By con-
trast, the study of genetic variation underlying addictions is able to
address causality, and is grounded on the premise that exposure to
various environmental influences – in combination with one's inher-
ent biology – determines the initial response to drugs as well as the
neuro-adaptations that contribute to the transition from casual use
to the addicted state [19].
1.2. The present study
The increasing recognition that complex traits and behaviors are
influenced by multiple genes has fostered the view that risk for com-
mon disorders is best considered in quantitative terms whereby rele-
vant genetic variants can be aggregated to reflect a polygenic liability
[20]. Nikolova et al. [21] were the first to use a biologically informed
“multilocus genetic profile score” (MLGP) — a composite genetic
index reflecting the influence of multiple functional polymorphic do-
pamine markers, which individually have been associated with varia-
tion in striatal dopamine signaling. They found that the MLGP score
accounted for a greater proportion of variance in ventral striatum re-
activity than did each locus considered independently.
Our first objective was to employ this novel genetic methodology
to the study of food addiction by investigating whether functional ge-
netic markers associated with elevated dopamine signaling distin-
guished those with YFAS-diagnosed food addiction from controls.
Based on prior evidence that the former group have a greater hedonic
responsiveness to food [8], we anticipated they would also have a
higher MLGP score than their control counterparts. Our second aim
was to assess whether the MLGP score was also positively associated
with eating-related sub-phenotypes of food addiction, such as binge
eating and food cravings, which have been identified in other re-
search [8]. To test this hypothesis, we included an assessment of the
five eating behaviors (viz. hedonically-driven eating, binge eating,
emotional eating, food cravings, and snacking on sweets) that differ-
entiated YFAS cases from controls in our recent study of food addic-
tion [8].
2. Methods
2.1. Participants
One hundred and twenty adults (women: 82; men: 38) between
the ages of 25 and 47 years took part in the study. Participants were
recruited from posters placed at public institutions soliciting volun-
teers for an overeating/overweight study. Advertisements were also
placed in local newspapers and online sites like CraigsList. Partici-
pants were required to have lived in North America for at least five
years prior to their enrolment. Women were also required to be
pre-menopausal as identified by the self-reporting of regular men-
strual cycles, and not to have had a pregnancy within the previous
six months. Exclusion criteria included a current diagnosis of any psy-
chotic disorder, substance abuse, or a serious medical/physical illness
such as cancer or heart disease. In this sample, 24% of participants met
the diagnostic criteria for BED according to the criteria proposed for
the soon-to-be-released DSM-5 [22]. The procedures employed in
this study were approved by the institutional Research Ethics and
were carried out in accordance with the Declaration of Helsinki.
2.2. Measures
Food addiction: Although there are no formally-recognized diag-
nostic criteria for food addiction, researchers have developed a
psychometrically-sound measure which operationalizes ‘food addic-
tion’ [9]. Preliminary evidence suggests that the Yale Food Addiction
Scale (YFAS) has high convergent validity with other measures of eat-
ing pathology, especially binge eating, and may therefore be a useful
tool to identify individuals with addictive tendencies towards food.
This 25-item scale was designed to operationalize food addiction
according to the 7 symptoms of substance dependence listed in the
DSM-IV, and modified for eating behaviors. The YFAS provides two
scoring options — a dichotomous and a continuous version. Similar
to the DSM substance-dependence criteria, a diagnosis of food addic-
tion is given if the respondent experienced three or more symptoms
over the past year, and if the “clinically significant impairment” crite-
rion is met. The dimensional score is the total number of symptoms
endorsed and ranges from 0 to 7. For this sample, Cronbach's alpha
coefficient was 0.922.
In a more recent YFAS validation study, the high symptom group
demonstrated faster reaction times in response to food cues versus
neutral cues, and reported higher attentional impulsivity, compared
to the low symptom group [23]. The one-factor structure of the
YFAS, and its high internal consistency, has also been confirmed in a
study using the German version of this scale [24].
Other important findings related to YFAS validation come from a
case–control study where those who met the diagnostic criteria for
food addiction had a significantly greater prevalence of BED, of severe
depression, and reported more pronounced symptoms of ADHD com-
pared to their obese counterparts [8]. In addition, they reported more
intense food cravings and greater emotional overeating. They were
also more impulsive than the obese controls.
 C. Davis et al. / Physiology & Behavior 118 (2013) 63–69 65

Multilocus genetic profile (MLGP) scores were based on six known Hedonically-driven eating was assessed by the Power of Food Scale
dopamine-related polymorphisms, all of which have been linked to [37], a 21-item questionnaire that reflects individual differences in
functional changes in brain dopamine transmission and/or responsive- the appetitive responsiveness to food in environments replete with
ness of the ventral striatum. According to Nikolova et al. [21], genotypes highly palatable food — independent of their actual consumption of
associated with relatively increased striatal dopamine-signaling them. In other words, it differentiates the motivation and appetitive
strength were given a score of 1; those with relatively low signaling, a drive to obtain food from the tendency to (over)eat food. Cronbach's
score of 0; and in the case where a genotype is associated with interme- alpha coefficient in this study was 0.97.
diate signaling strength, a score of 0.5 was given (see Table 1). The Binge eating was assessed by 5-items of the Binge Eating Question-
MLGP score for each participant is the sum of the score at each locus, naire [38], which obtains information about frequency and severity of
with a range from 0 to 6. symptoms such as loss-of-control over eating, and negative affect fol-
Taq1A is a C/T single nucleotide polymorphisms [SNP] (rs1800497) lowing a binge. The alpha coefficient for this study was 0.76.
located in the ankyrin repeat and kinase-domain containing 1 gene Emotional eating was assessed by the Dutch Eating Behavior Ques-
(ANKK1), downstream of the DRD2 region on chromosome 11. Relative tionnaire [DEBQ] [39]. This subscale reflects the degree to which eat-
to the T (A1) allele, the C (A2) has been associated with relatively in- ing is prompted by emotional states like tension and worry rather
creased DA signaling [25] and increased striatal glucose metabolism than by hunger. The alpha coefficient in the present study was 0.96.
[26] due to the relationship of the A1 allele with reduced D2 receptor Food cravings were assessed by the Food Craving Questionnaire —
binding affinity and lower striatal receptor densities [27]. It is frequently Trait [40]. The 39-items reflect evidence that food cravings can be
reported that A1 is inherited dominantly [28], so both the A1/A1 and expressed both physiologically and psychologically — for example,
A1/A2 genotypes were given a score of 0. as feelings of hunger, preoccupation with food, and lack of control.
−141C Ins/Del is a SNP (rs1799732) located in the promoter re- The alpha coefficient was 0.97.
gion of DRD2. The DelC minor allele has been associated with signifi- Snacking on sweets was assessed by the 6-item subscale of the Eat-
cantly less promoter activity and protein expression of DRD2 [29], ing Behaviors Patterns Questionnaire [41], which was designed to mea-
and with increased ventral striatal reactivity [30]. sure the frequency and quantity of sugary snacks consumed between
DAT1 is a 40-base pair variable number tandem repeat (VNTR) normal meals. The alpha coefficient was 0.77.
polymorphism within the 3′ untranslated region of the dopamine
transporter gene (SLC6A3). In comparison with 10-repeat homozy-
2.3. Genotyping
gotes, the 9-repeat allele of this polymorphism has been linked to re-
duced transporter protein expression and therefore greater dopamine
A venous blood sample (20–30 ml) was collected from each sub-
availability in the synapse [31], as well as increased ventral striatal re-
ject, and the non-enzymatic, high salt procedure was used to extract
activity [30].
DNA from the whole blood [42]. The ANKK1/DRD2 markers
Val 158Met is a functional SNP (rs4680) within the 3rd exon of the
(rs1800497 [Taq1A], rs6277 [C957T], and rs12364283), and the
catechol-O-methyltransferase gene (COMT) involving a substitution
COMT Val 158Met (rs4680) SNP were genotyped using Applied
of valine to methionine at position 158. The Met allele has been asso-
Biosystems Inc. (AB; Life Technologies, Burlington, ON) TaqMan
ciated with a 3 to 4-fold reduction in dopamine catabolism and there-
pre-designed assays. For each reaction, 20 ng genomic DNA was am-
fore higher dopamine levels [31], and with increased activation in
plified as per manufacturer's directions scaled to a total volume of
neural midbrain areas including the basal ganglia and limbic regions
10 μl in an AB 2720 thermal cycler. Post-amplification products
[32].
were analyzed on the ABI Prism 7500 Sequence Detection System
C957T (rs6277) is a SNP in exon 7 of the DRD2 gene, and is associ-
using the allelic discrimination option, and genotype calls were deter-
ated with DRD2 binding potential in the striatum with the highest in
mined manually by comparing to six no template controls [43]. The
the homozygous T genotype [33]. Changes in DRD2 availability ap-
DRD2 rs1799732 [− 141delC] was genotyped in the same manner
pear to be driven by alterations in receptor affinity and thereby in
using a custom designed TaqMan assay [forward primer: 5′ CAA
striatal dopamine levels [34,35].
AAC AAG GGA TGG CGG AAT C; reverse primer 5′ CCA CCA AAG
rs12364283 is a T/C SNP in the promoter region of DRD2. The
GAG CTG TAC CT; reporter 1 sequence (VIC): 5′ TAC CCG TTC CAG
minor T allele is associated with increased transcription and D2 re-
GCC G; reporter 2 sequence (FAM): 5′ CTA CCC GTT CAG GCC G].
ceptor density [36].
For the DAT1 VNTR, total genomic DNA (60 ng) was combined
with 1 × MBI Fermentas PCR buffer containing KCl, 1.5 mM MgCl
Table 1 (MBI Fermentas), 0.13 μg each primer (Vandenberg et al. 1992; for-
Composition and distribution of MLGP scores.
ward primer labeled with 5′ NED fluorescent tag), 10% DMSO
Polymorphism Genotypes N DA profile scores (Sigma-Aldrich), 0.16 mM each dNTP (MBI Fermentas) and 2 U Taq
DRD2 Taq1A A1+ 54 Low
polymerase (MBI Fermentas) to a total volume of 25 μl in a 96-well
A1− 66 High PCR plate. The PCR reactions were subjected to an initial denaturation
DRD2 −141C Ins/Del Del+ 39 High for 5 min at 95 °C, followed by 35 cycles of amplification in an AB
Ins/Ins 81 Low 2720 thermal cycler: denaturing for 30 s at 95 °C, annealing for
DAT1 VNTR 9-repeat 56 High
1 min at 65 °C and extension for 30 s at 72 °C. Reaction products
10/10 64 Low
COMT Val158Met Met/Met 14 High were electrophoresed on an AB 3130-Avant Genetic Analyzer as per
Val/Met 58 Intermediate manufacturer's directions, and product sizes determined by compari-
Val/Val 48 Low son to 2500 ROX size standard using GeneMapper (version 4.0).
C957T C− 26 High
C+ 94 Low
rs12364283 T+ 23 High 2.4. Procedures
T− 97 Low

Individual MLGP scores represent the sum of the value assigned to each DA genotype
across the six functional polymorphic loci included in this study. ‘High’ genotypes re-
ceived a score of 1; ‘intermediate’ a score of 0.5; and ‘low’ genotypes a score of 0.
For example, an individual with the following polymorphisms: A1+ (Taq1A), Del+
(−141C Ins/Del), 9-repeat (DAT1 VNTR), Met/Met (COMT Val158Met), C− (C957T),
and T+ (rs12364282) would have a MLGP score of 5 (0 + 1 + 1 + 1 + 1 + 1).
On the day of testing, informed consent was obtained, and all rel-
evant demographic information obtained in a face-to-face interview.
A structured clinical interview was also carried out to confirm eligibil-
ity. Height and weight were measured with the participant standing
in stocking feet and wearing light indoor clothing, and the blood
66 C. Davis et al. / Physiology & Behavior 118 (2013) 63–69

sample was taken at the hospital laboratory. The questionnaire pack-
age was completed at home and returned at a later date.
2.5. Statistical analyses
Group differences were tested using between-subjects analysis of
variance (ANOVA), and bivariate correlations were used to assess the
association between MLGP score, eating behaviors and BMI. In order
to test simultaneously whether the eating behaviors acted as media-
tors of the MLGP and YFAS-diagnosis relationship, a multiple media-
tion model was tested according to the procedures described by
Preacher and Hayes [44]. Multiple mediation analyses assess the sig-
nificance of the indirect pathways via putative mediators as well as
the overall mediation model. Only those mediators with significant
association with the MLGP were used in further tests of mediation
(see Results).
As shown in Fig. 1, Path c refers to the total effect of MLGP on YFAS
in the absence of the mediators. Specific indirect effects refer to the in-
fluence of path a × path b via each specific mediator (a1 × b1 is the in-
direct effect of MLGP on YFAS diagnosis via food cravings; a2 × b2 is
the indirect effect of MLGP on YFAS diagnosis via binge eating;
a3 × b3 is the indirect effect of MLGP on YFAS diagnosis via emotional
eating). Multiple mediation analysis allows statistical control over the
correlations between the specific indirect effects: thus, each specific
indirect effect is analogous to B weights in multiple regression models
and reflects the unique indirect effect via a specific mediator. The total
indirect effect reflects the summation of the specific indirect effects.
Similar to R in a multiple regression analysis, the total indirect effect
tests whether eating behaviors, as a group, mediate the association
between MLGP and food addiction diagnosis. Path c′ refers to the di-
rect effect of MLGP on YFAS when also controlling for the mediators.
Bias-corrected bootstrap confidence intervals (n = 5000, confi-
dence intervals set at 95%) were used to assess the significance of in-
direct effects. This procedure overcomes the potential violation of the
assumption of multivariate normality inherent in tests of paths of in-
direct effects that use product terms, and it allows statistical control
over covariates — of key importance given the high correlations be-
tween the potential mediators in the present model. This approach
also allows for the estimation of indirect effects when including di-
chotomous dependent variables such as the presence or absence of
a diagnosis, and derives pseudo-R 2 estimates. The SPSS “INDIRECT”
macro developed to accompany the paper by Preacher and Hayes
[44] was used to test the significance of the overall total indirect effect
and the specific individual indirect pathways. The absence of zero in
the confidence interval indicates significant indirect (i.e., mediated)
effects.
3. Results
3.1. Food addiction diagnosis
According to the YFAS diagnostic scoring procedure, 21 adults
(female = 16; male = 5) were classified with food addiction.
3.2. Descriptive statistics and group differences
Prior to analysis, all data were screened for potential outliers and
normality. None of the variables deviated significantly from normal,
nor were there any univariate or multivariate outliers. Means and
standard deviations for all quantitative variables are displayed in
Table 2, listed separately by YFAS-diagnostic status.
As shown in Table 2, and as we predicted, the MLGP score was sig-
nificantly higher in the food-addiction group than in the controls.
Similar to our previous study [8], the food-addiction group also had
higher scores on the five eating-behavior variables. As shown in
Table 3, the associations among the eating variables were all highly
statistically significant. The eating behaviors were also positively
correlated with the MLGP score, except snacking-on-sweets and
hedonically-driven eating, the latter of which showed a trend towards
significance. These results largely supported our prediction that the
MLGP score would be related to eating-related sub-phenotypes of
food addiction.
Encouraged by the findings described above – and with a view to
investigating the mechanisms linking one's genetic predisposition to
a pathological dependence on palatable food – we decided to test a

YFAS
MLGP
Diagnosis
c = .50*

Cravings

Binge
Eating

Emotional
Eating

YFAS
MLGP
Diagnosis

c’ = .14

Total Indirect effect (bias corrected 95% CI: .08–1.12; NagelKerke R2=0.58; N=117)

Fig. 1. Multiple mediation model (i.e., the effect of the other mediators has been partialled) with Gender as a control. Note. a = unstandardized IV to Med coefficient, b =
unstandardized Med to DV coefficient, c = unstandardized total effect (IV to DV), c′ = unstandardized direct effect. Subscripts refer to specific indirect paths. YFAS diagnosis
coded 1 = yes, 0 = No.
 C. Davis et al. / Physiology & Behavior 118 (2013) 63–69 67

Table 2
Means and standard deviations (SD) for all quantitative variables, listed separately for FA and non-FA.

FA Non-FA

Variable Mean SD Range Mean SD Range F p

Multilocus score 2.6 1.0 0–5.5 2.0 1.1 0–5 5.201,118 0.023
Hedonic eating 82.6 14.4 48–103 51.7 17.8 21–94 55.261,117 b0.0001
Binge eating 3.8 1.4 1–5 1.6 1.6 0–5 33.741,116 b0.0001
Emotional eating 4.0 0.8 1.8–5 2.8 1.0 1–5 26.201,117 b0.0001
Food craving 176.8 27.6 114–224 115.9 34.4 41–196 55.071,116 b0.0001
Sweet snacking 23.0 5.0 13–30 17.4 4.2 7–25 28.471,116 b0.0001
Age 34.7 5.9 25–44 32.5 6.6 25–47 2.081,118 0.152
BMI 35.5 7.3 22–49.4 33.1 8.9 19–60 1.281,118 0.250

FA = those diagnosed with food addiction according to the YFAS.

Non-FA = those who did not meet diagnostic criteria for YFAS food addiction.
BMI = body mass index (weight [kg] / height [m2]).

multiple mediation model proposing that patterns of reward-driven of BED in those with YFAS food addiction, it is important to note
overeating facilitate this relationship (see Fig. 1). that larger brain-activation differences in the amygdala and ventral stri-
atum have also been found in obese adults with BED compared to
3.3. Mediation weight-matched controls. These results suggest a greater motivational
sensitivity to, and visual processing of, palatable food cues in the BED
Tests of the indirect effect via each specific mediator and as a group [46]. Other case–control research has found similar heightened
group (total indirect effects) are shown in Table 4. Indirect effects responses to food cues in brain areas associated with reward in those
are considered significant if the confidence intervals do not contain with BED [47].
zero. Since potential mediators must correlate significantly with Although the current study adds to accumulating endorsement of
MLGP scores (a paths) and YFAS diagnosis (b paths) for inclusion in food addiction as an identifiable clinical entity with many similarities
a mediation model, only food cravings, binge eating and emotional to drug-addiction disorders [8], there remains the question of whether
eating were tested. Gender was entered as a covariate in the model. 1 it is simply a more severe form of BED. This issue is especially relevant
The overall mediation model was statistically significant as indi- in light of their substantial overlap, and the co-morbid and dis-
cated by the absence of zero in the confidence interval for the total in- tinguishing characteristics they have in common [8,9]. In a recent
direct effect (95% CI: 0.00–1.12). However, only the food craving scale study, and as an initial attempt to address this issue, we compared
produced a significant specific indirect effect (95% CI: 0.04–0.93) after two equivalent groups of overweight men and women with BED on var-
controlling for binge eating and emotional eating, neither of which ious demographic characteristics, patterns of overeating, personality
were significantly unique mediators. 2 There was, however, a trend to- risk factors, and co-morbid clinical symptoms — one group with
wards a significant indirect effect via binge-eating. Together, the co-occurring YFAS-diagnosed food addiction and the other without
MLGP and the three mediators accounted for approximately 58% of [48]. The two groups were equivalent in age and BMI, as others have
the variance in YFAS diagnosis (Nagelkerke pseudo R 2 = .577). The found [49]. However, the BED group with food addiction reported
total indirect effects accounted for 71% of the total (non-mediated) more severe binge eating, food cravings, hedonically-driven eating,
effect of MLGP and YFAS diagnosis ((.5036 − .1434) / .5036). and emotional and external overeating. They were also more impulsive,
had more addictive personality traits, and displayed greatly elevated
4. Discussion symptoms of depression compared to the BED group without
co-morbid food addiction. All these differences were highly statistically
This study is the first to investigate genetic differences between significant. In a secondary analysis, and in comparison to a group of
those with YFAS-food addiction and non-affected controls. As such,
it offers fresh and supportive evidence that reward responsiveness
Table 3
is a high-risk endophenotype for this condition. The mediation Bivariate correlation matrix for the MLGP score, eating-behavior variables, and BMI,
model we tested demonstrated that enhanced dopamine-signaling, with p-values presented in parentheses.
as implied by the proxy MLGP score, was significantly stronger in
Variable MLGP Binge Hedonic Emotion Snack Crave BMI
the food-addiction group than in controls, and that this relationship
was mediated by greater food cravings, bingeing, and emotional eating. MLGP .23 .15 .23 .10 .21 .05
(0.011) (0.096) (0.011) (0.285) (0.021) (0.565)
In other words, our data strongly supported a reward-based causal
Binge .67 .55 .32 .68 .35
model progressing from an inherent biological susceptibility, to in- (b0.001) (b0.001) (0.001) (b0.001) (b0.001)
creased risk for overeating, and ultimately to addictive tendencies to- Hedonic .52 .48 .83 .29
wards certain food. (b0.001) (b0.001) (b0.001) (0.002)
Our findings mesh well with the only YFAS neuroimaging study, Emotion .25 .67 .34
(0.006) (b0.001) (b0.001)
which showed that reward-circuitry activation in the caudate and Snack .49 .08
amygdala, in response to the anticipated receipt of food, correlated pos- (b0.001) (0.367)
itively with symptom scores [45]. Given the substantial co-occurrence Crave .27
(0.003)
1 BMI
Gender was also tested as a potential moderator in the multiple-mediation model.
There was no evidence of a moderating effect of gender. Therefore, gender was added MLGP = multilocus genetic profile.
as a covariate rather than as a moderator. Binge = Binge Eating Questionnaire.
2
The three mediators were also run in single mediator models. The indirect effect Hedonic = Power of Food Scale.
via all three eating behaviors (when not controlling for the other eating behaviors) Emotion = Dutch Eating Behavior Questionnaire — Emotional Eating subscale.
were all significant (food craving unstandardized indirect effect BC 95% CI: .06–.82; Snack = Eating Behaviors Pattern Questionnaire — Snacking on Sweets subscale.
binge-eating unstandardized indirect effect BC 95% CI: .02–.55; emotional eating Crave = Food Craving Questionnaire — Trait.
unstandardized indirect effect BC 95% CI: .06–.60). BMI = body mass index.
68 C. Davis et al. / Physiology & Behavior 118 (2013) 63–69
Table 4
Indirect of MLGP on YFAS food-addiction status through eating behaviors, controlling
for gender.
Mediator Bootstrap SE BCa 95% CI BCa 95% CI
estimate lower upper
Specific indirect effects
Food cravings .43⁎ .28 .04 .94
Binge eating .23 .19 −.01 .65
Emotional eating .06 .20 −.32 .49
Total indirect effect .72⁎ .35 .08 1.12
N.B. Based on 5000 bootstrap samples. BCa = biased corrected and accelerated; CI =
confidence interval. Food cravings, binge eating, and emotional eating bootstrap esti-
mates represent the unique indirect effects via each mediator while controlling for
the other two mediators. Total indirect effect = unstandardized indirect effect of all
three specific indirect effects (i.e. food cravings, binge eating, and emotional eating)
combined.
⁎ Indirect effect is significantly different from zero.
obese adults without a diagnosis of BED or food addiction, the BED
group without food addiction did not differ on any of the variables ex-
cept bingeing, food cravings, and hedonic eating.
Clearly, replication of these results and extended investigations
are needed before any firm conclusions can be drawn. Whether the
two diagnostic entities are sufficiently different in etiology and clini-
cal course to warrant their classification as separate pathological phe-
notypes of obesity can also be better established by complete factorial
designs that assess BED and food addiction as main effects and are
able to test their possible interaction. Better clarity on this issue is
an important next-step in eating-disorder and addiction research,
and will have important consequences for developing appropriate
treatment strategies for those who struggle with compulsive overeat-
ing. For instance, in a recent study of weight-loss treatment-seeking
adults, YFAS-symptom scores related significantly to increased de-
pression, emotional eating, and binge eating [50]. Increased symp-
tomatology was also related to less weight loss after several weeks
of treatment, suggesting that food addiction, with related signs of tol-
erance and withdrawal, may undermine efforts to lose weight in
those trying to adopt better eating habits.
In summary, our findings have provided support for the view that
genetic variation associated with enhanced dopamine signaling gives
rise to an elevated responsiveness to palatable food, and that together
they may be causal factors in the development of an addiction to
hyper-palatable food. A substantial body of preclinical research has
demonstrated biobehavioral changes, such as increased incentive
salience, that occur from excessive engagement with dopamine-
stimulating activities like eating calorie-dense foods [51]. The likelihood
of this process developing in vulnerable individuals is almost certainly
increased in the current marketplace with its superfluity and ready
availability of highly palatable food.
Despite the novel genetic and statistical approaches used to study
food addiction in this study, it is important to emphasize the relative-
ly small number of participants who met the diagnostic criteria for
food addiction compared to the size of the control group. Therefore,
replication of our genetic mediation model is greatly encouraged be-
fore firmer conclusions can be drawn. It is also important to acknowl-
edge that the MLGP score assumes an additive contribution of the
genetic indicators — an inference that may not be valid because the
various markers could combine interactively to affect striatal respon-
siveness. As genetic research becomes more sophisticated, investiga-
tors will be better able to assess such possibilities. In addition, the
MLGP score is only a proxy index of dopamine signaling and ventral
striatal responsiveness. Therefore, while our biological findings sup-
port the model we tested, they should be viewed as tentative at
best. It is also important, when interpreting these results, to be mind-
ful of the complexities of brain dopamine pathways and the many
motivational processes regulated by this neural circuitry, including
reward seeking, cue-related learning, incentive motivation, and stim-
ulus salience [52]. For example, it is possible that increased ventral
striatal dopamine release does not mediate appetite or food intake di-
rectly, but instead serves to promote food-related learning or to en-
hance the tendency to engage in food-seeking behaviors [52].
In addition, all the eating-related behaviors were assessed by
self-report measures, which have the potential of introducing
self-serving and recall biases. Future studies would be advised to in-
corporate more objective laboratory measures of eating behaviors,
and other in-the-moment techniques such as ecological momentary
assessment to collect data on binge eating, cravings, snacking, and
emotional eating. Although these measures come with their own spe-
cific limitations, converging evidence from many different sources
will add important confirming evidence to the findings of the present
study.
4.1. Conclusions
While evidence for the validity of the food-addiction construct is
rapidly gaining ground, inevitably this perspective has also found its de-
tractors [53–56]. Unfortunately, in presenting their arguments, some of
those participating on the negative side of the debate have used terms
like overeating, obesity, and food addiction interchangeably — an
issue which has obscured their distinctiveness. There are no explicit as-
sertions in the concept of food addiction that more than a subset of the
population could, or would, be affected by this putative condition –
even among those who excessively overeat and are obese – in the
same way as it would be illogical to maintain that all heavy drinkers
are alcoholics. Most individuals who use addictive substances – drugs
or highly palatable food – do not develop dependence, even though
the related symptoms of this condition exist in the general population
along a continuum of varying magnitude or severity. Many factors con-
tribute to an individual's propensity to, or risk for, addiction disorders,
and no single set of influences can account for every stage in the process
from initial use to chronic abuse.
Acknowledgments
This study was funded by a grant (MOP- 84257) from the Canadian
Institute of Health Research.
Declaration of interests
The authors report no conflicts of interest. The authors alone are
responsible for the content and writing of the paper.
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