Psychological Medicine, 2001, 31, 635–645.
" 2001 Cambridge University Press
Printed in the United Kingdom
Deriving behavioural phenotypes in an international,
multi-centre study of eating disorders
T H E P R I C E F O U N D A T I O N C O L L A B O R A T I V E G R O U P ", #
ABSTRACT
Background. An international, multi-site study funded by the Price Foundation has collected 237
affected relative pairs to identify potential genetic factors that may contribute to the pathogenesis
of anorexia nervosa (AN). The current report utilized this sample to derive phenotypes from the
personality and behavioural traits assessed in a large number of individuals with eating disorders.
Methods. Multivariate analytical techniques were used to characterize the relationships among
personality (e.g. trait anxiety, perfectionism, harm avoidance, novelty seeking) and behavioural
traits (obsessions and compulsions) in individuals with eating disorders (primarily AN ; N l 348)
and assess the effectiveness of these traits in classifying subjects into diagnostic subtypes.
Results. Factor analysis revealed that the most influential factor was one of trait anxiety, harm
avoidance, perfectionism, obsessive–compulsive behaviours, and diminished self-directedness,
although the precise nature of this factor differed slightly across sites. Discriminant analysis was
used to evaluate the utility of these personality\behavioural factors in predicting subdiagnosis.
Overall, the misclassification rate was 34 % ; however, there was an 80 % rate of accurate
classification of those individuals with a diagnosis of restricting-type AN.
Conclusions. Trait anxiety, harm avoidance, perfectionism, obsessive–compulsive behaviours and
diminished self-directedness may best be conceptualized as parts of the same underlying construct
among individuals with eating disorders, particularly AN. These personality and behavioural traits
were also found to be of some utility in classifying eating disordered individuals into diagnostic
subgroups, particularly those with restricting-type AN. We expect these phenotypic findings to
benefit our ongoing search for genetic loci underlying the liability to eating disorders.
" The investigators in this multi-site study group are : Dr L. R. R.
Lilenfeld, Department of Psychology, Georgia State University,
Atlanta, GA, USA ; Drs B. Devlin, S. Bacanu and W. H. Kaye,
Western Psychiatric Institute and Clinic, University of Pittsburgh
School of Medicine, Pittsburgh, PA, USA ; Dr C. M. Bulik, Virginia
Institute for Psychiatric and Behavioural Genetics, Department of
Psychiatry, Virginia Commonwealth University, Richmond, VA,
USA ; Dr M. Strober, Neuropsychiatric Institute and Hospital,
School of Medicine, University of California at Los Angeles, Los
Angeles, CA, USA ; Dr W. H. Berrettini, Center for Neurobiology
and Behavior, Department of Psychiatry, University of
Pennsylvania School of Medicine, Philadelphia, PA, USA ; Dr M. M.
Fichter, Klinik Roseneck, Hospital for Behavioural Medicine,
Munich, Germany ; Dr D. Goldman, National Institute on Alcohol
Abuse and Alcoholism, National Institutes of Health, Bethesda,
MD, USA ; Dr K. A. Halmi, New York Presbyterian Hospital
– Westchester, Weill Medical College of Cornell University, White
Plains, NY, USA ; Drs A. Kaplan and D. B. Woodside, Department
of Psychiatry, The Toronto Hospital, Toronto, Canada ; and Dr J.
Treasure, Institute of Psychiatry, Maudsley and Bethlem Royal
Hospital, London, UK.
# Address for correspondence : Dr Walter H. Kaye, Western
Psychiatric Institute and Clinic, 3811 O’Hara Street E-724,
Pittsburgh, PA 15213, USA.
INTRODUCTION
Psychometric studies have consistently linked
anorexia nervosa (AN) to a cluster of moderately
heritable (Heath et al. 1994) personality and
temperamental traits, specifically, obsessionality, perfectionism and harm avoidance
(Strober, 1980 ; Brewerton et al. 1993 ; Kleifield
et al. 1993 ; Waller et al. 1993 ; Sohlberg &
Strober, 1994 ; Vitousek & Manke, 1994 ; Bulik
et al. 1995 a ; Srinivasagam et al. 1995 ; O’Dwyer
et al. 1996 ; Lilenfeld et al. 1998 ; Von Ranson et
al. 1999 ; Kaye & Strober, 2000), as have earlier
writings (e.g. Palmer & Jones, 1939 ; DuBois,
1949). In this regard, it has been speculated that
phenotype similarities between these traits and
the rigidly persevering, obsessional and anxiety-
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reducing character of the anorexic’s dietary
restraint may be based upon shared genetic and
environmental factors (Strober, 1991, 1995 ;
Vitousek & Manke, 1994). These findings are
remarkably consistent across studies (Lilenfeld
& Kaye, 1998) and continue to characterize
individuals with AN even after recovery (Casper,
1990 ; Kaye et al. 1993 ; Srinivasagam et al.
1995). While such traits may be exaggerated by
starvation (Keys et al. 1950 ; Pollice et al. 1997),
their persistence after recovery supports the
speculation that such traits may be vulnerability
factors for AN, rather than merely consequences
of the disorder.
Personality traits associated with bulimia
nervosa (BN) have been less well-studied and
appear more heterogeneous ; however, certain
consistencies are evident. While impulsivity and
emotional instability are more common in BN
than AN (Casper et al. 1980 ; Garfinkel et al.
1980 ; Strober, 1981), traits such as harm
avoidance, compulsivity, perfectionism and
obsessionality are prominent (Vitousek &
Manke, 1994 ; Bulik et al. 1995 a ; Joiner et al.
1997) and often persist after clinical recovery
(Kaye et al. 1998). The common occurrence of
particular personality traits in AN and BN,
especially those associated with anxiety and
restraint, converges with evidence of significant
co-morbidity between AN and BN (Kendler et
al. 1991 ; Walters & Kendler, 1995), the frequency in both of antecedent anxiety disorders
(Deep et al. 1995 ; Bulik et al. 1996, 1997 a) and
evidence of serotonergic hyperactivity in both
disorders after long-term clinical recovery (Kaye
et al. 1991, 1998).
Research using twin and adoption study
methodology suggests that a broad range of
personality traits are heritable, with perhaps
50 % of measured personality variation attributed to genetic diversity (Tellegen et al. 1988).
A heuristic model proposed by Cloninger (1986)
hypothesizes the existence of three core
dimensions underlying most personality variation. Importantly, four independent studies
(Brewerton et al. 1993 ; Kleifield et al. 1993 ;
Waller et al. 1993 ; Bulik et al. 1995 b) converge
in showing that one particular dimension on the
Temperament and Personality Questionnaire
(TPQ) (Cloninger, 1986), namely harm avoidance, is significantly elevated in both AN and
BN subjects compared to normal controls. This
commonality is consistent with aetiological
models positing the role of phobic anxiety as a
predisposing factor in these conditions (Vitousek
& Manke, 1994).
The overarching goal of these collaborative
studies (Kaye et al. 2000) is to identify genes that
may influence susceptibility to AN. Belmaker &
Biederman (1994) suggest that it may be more
prudent to search for genetic markers of personality traits (e.g. behavioural inhibition) as
expressions of genetic vulnerability to psychopathology than to look for markers of specific
illness, as defined solely by psychiatric diagnosis. This may be particularly applicable to
restricting-type AN, which may have the most
homogeneous personality presentation of any
psychiatric illness (Vitousek & Manke, 1994 ;
Strober, 1995). Thus, our collaborative studies
(Kaye et al. 2000) will correlate personality and
behavioural traits, as well as psychiatric diagnosis, with genotypes. The goal of the current
report was to utilize a multivariate analytical
approach to improve the characterization
of behavioural phenotypes of our subjects.
This was accomplished by examining the
inter-relationships among personality and
behavioural traits and evaluating the utility of
these traits in classifying subjects in our sample.
The concise characterization of these personality
and behavioural traits will aid in the search for
liability loci.
METHOD
Study design and collaborative arrangements
In an effort to map genetic susceptibility loci
involved in AN, and international, multi-site
study, funded by the Price Foundation, was
designed (Kaye et al. 2000). This study utilized
affected relative pairs to identify genetic factors
that might contribute to the pathogenesis of
AN. In the Kaye et al. (2000) study, all probands
met modified DSM-IV (American Psychiatric
Association, 1994) criteria for AN, whereas all
affected first-, second- and third-degree relatives
met modified DSM-IV criteria for AN, DSM-IV
BN, or eating disorder not otherwise specified
(NOS) (refer to ‘ Participants ’ section).
The investigators, using a collaborative consensus, selected a battery to assess psychological
Deriving behavioural phenotypes of eating disorders
and personality features that have been shown
to be associated with, and may underlie vulnerability to, eating disorders. In general, we
attempted to evaluate persistent traits rather
than personality features confined to the acute
phase of the illness (Brewerton et al. 1993,
Kleifield et al. 1993, Bulik et al. 1995 a,
Srinivasagam et al. 1995 ; O’Dwyer et al. 1996 ;
Kaye et al. 1998 ; Von Ranson et al. 1999). These
traits included harm avoidance, perfectionism,
and anxiety.
Six sites in North America and Europe were
identified that had well-established programmes
for the treatment of AN. The sites included
University of Pittsburgh (W. H. K.), Cornell
University (K. A. H.), University of California
at Los Angeles (M. S.), University of Toronto
(A. K. and D. B. W.), University of Munich
(M. M. F.) and University of London (J. T.).
An additional site, Thomas Jefferson University
in Philadelphia (W. H. B.), was included for its
expertise in molecular genetic research on
psychiatric illness. See Kaye et al. (2000) for a
complete description of the overall study design.
Participants
The subjects reported in this manuscript (N l
348) are a subset of the sample from the multisite project (Kaye et al. 2000). This manuscript
reports on all AN probands (N l 196) and their
siblings who had a lifetime diagnosis of modified
DSM-IV AN (N l 116) or DSM-IV BN (N l
36). All other relatives from the original sample
(e.g. half-siblings, cousins, aunts, uncles), as well
as siblings with a diagnosis of NOS, were
excluded in the current report. Our reasoning
for this sampling approach is as follows. Both
genetic and environmental effects on the correlation of personality\behavioural traits should
be consistent within full siblings and greater
than these effects on more distant relative pairs,
such as aunt–niece pairs. Thus, in statistical
terms, observations of sibling-pairs are exchangeable across pairs (i.e. the identity of the
pairs is irrelevant), but a sibling-pair and
aunt–niece pair are not exchangeable. By analysing only full siblings we maintain the majority
of the sample while also meeting this important
statistical criterion of exchangeability.
Probands were required to meet the following
criteria for acceptance into the study : (a) an
637
unequivocal lifetime ‘ core ’ diagnosis of AN by
DSM-IV criteria, waiving the single criterion of
amenorrhoea for 3 consecutive months, since
some subjects were menstruating due to treatment with exogenous hormone replacement and
some were male ; (b) age between 13 and 65 ; and
(c) fulfilment of AN diagnostic criteria for not
less than 3 years prior to ascertainment. Exclusion criteria included a lifetime history of any
of the following : organic brain syndrome ; IQ
70 ; dementia, schizophrenia ; bipolar illness ;
obesity ; medical illness that could affect appetite,
eating behaviour, or body weight (e.g. diabetes) ;
DSM-IV binge eating disorder, and any
‘ regular ’ binge eating. The latter was defined as
bingeing at least once weekly for 3 or more
consecutive months. All siblings had similar
exclusion criteria, with the exception of binge
eating, as some of these subjects had bingeing
symptomatology in the context of an AN
diagnosis and some had a BN diagnosis. BN
diagnoses were made according to DSM-IV
criteria.
Assessment instruments
The assessment battery was selected, based on
existing literature, to include those personality
and behavioural features most consistently
associated with eating disorders and not confined
to the acute phase of the illness (Brewerton et al.
1993 ; Kleifield et al. 1993 ; Waller et al. 1993 ;
Bulik et al. 1995 a ; Srinivasagam et al. 1995 ;
O’Dwyer et al. 1996 ; Kaye et al. 1998 ; Von
Ranson et al. 1999). However, we did ask
subjects to report some behaviours (e.g.
obsessions and compulsions) at the time when
their eating disorder was at its worst in order to
access the maximum lifetime severity of the
behaviour. Methods for interviewer training and
reliability are described elsewhere (Kaye et al.
2000).
Eating disorder diagnostic assessment
Structured Interview of Anorexia Nervosa
and Bulimic Syndromes (SIAB)
This instrument was used to assess lifetime
history of eating disorders among probands and
affected relatives. The SIAB (Fichter et al. 1998)
is a detailed structured interview schedule that
derives eating disorder diagnostic information,
as well as additional psychopathological factors
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The Price Foundation Collaborative Group
related to eating disorders. The internal consistency of the six SIAB subscales on the lifetime
version of the instrument is moderate to high,
with Cronbach’s alpha ranging from 0n64 to 0n89
(Fichter et al. 1998), and their inter-rater
reliability for these same subscales is excellent,
ranging between 0n80 and 0n90 (Fichter et al.
1998). No psychometric information has yet
been published on the English translation of the
SIAB. Subjects were asked to report ‘ worst
lifetime ’ symptoms.
Behavioural assessments
Yale–Brown Obsessive–Compulsive Scale (YBOCS)
The Y-BOCS (Goodman et al. 1989) is a semistructured interview designed to rate the presence and severity of obsessive thoughts and
compulsive behaviours typically found among
individuals with obsessive–compulsive disorder
(OCD). It has excellent inter-rater reliability
(Goodman et al. 1989) and is considered to be
the ‘ gold standard ’ for measuring obsessive–
compulsive symptom severity (Pato et al. 1994).
There is a published German translation of this
instrument as well (Goodman et al. 1991).
Subjects were asked to report ‘ worst lifetime ’
symptoms.
Yale–Brown–Cornell Eating Disorder Scale
(YBC-EDS)
The YBC-EDS (Sunday et al. 1995) is similar
to the Y-BOCS ; however, it assesses core
obsessions and compulsions specific to eating
disorders (e.g. those related to food, eating,
weight and exercise). Excellent inter-rater reliability, internal consistency and convergent
validity have been demonstrated for the YBCEDS (Mazure et al. 1994). No psychometric
information has yet been published on the
German translation of the YBC-EDS. The YBCEDS was modified with the authors of the
instrument to assess ‘ worst lifetime ’ symptoms,
as well as current symptoms.
Self-report psychological symptom and
personality assessments
State-Trait Anxiety Inventory (STAI )
The STAI (Spielberger et al. 1970) is a widely
used instrument for the assessment of anxiety.
The state anxiety assessment asks subjects to
report how they feel ‘ at this moment ’ and the
trait anxiety assessment asks subjects to report
how they ‘ generally feel ’. There is also a
published German translation of this instrument
(Laux et al. 1981).
Multidimensional Perfectionism Scale (MPS )
The MPS (Frost et al. 1990) is a 35-item, factoranalytically developed self-rating instrument
that consists of an overall assessment of perfectionism, as well as six specific dimensions of
perfectionism. The coefficients of internal consistency for the factor scales range from 0n77 to
0n93 and the reliability of the overall scale is
0n90 (Frost et al. 1990). The MPS successfully
discriminates between subjects with and without
eating disorders (Srinivasagam et al. 1995). No
psychometric information has yet been published on the German translation of the MPS.
To assess worst lifetime symptom expression,
subjects were instructed to respond to the
questions according to how they felt at the time
when their concerns about eating and weight
were strongest.
Temperament and Character Inventory (TCI )
The TCI (Cloninger et al. 1993) is a 226-item
factor-analytically developed self-rating instrument that measures seven dimensions of
personality. The TCI is an extension of
the Tridimensional Personality Questionnaire
(TPQ) (Cloninger et al. 1991), which assesses the
temperament dimensions of novelty seeking,
harm avoidance and reward dependence
(Cloninger et al. 1991). The authors’ original
model has been extended to measure the
additional temperament factor of persistence
and the three character dimensions of
self-directedness, cooperativeness, and selftranscendence. The internal consistency of all
seven scales is high, ranging from 0n76–0n89
(Cloninger et al. 1993). There is a published
German translation of the TCI as well
(Cloninger et al. 2000).
Procedure
Subjects were recruited through several sources,
including : (1) identification of potential subjects
through clinic data bases ; (2) referrals from
clinicians with knowledge of the study ; (3)
advertisement in a variety of different media at
local and national levels. Potential subjects were
first screened to determine study suitability. If a
Deriving behavioural phenotypes of eating disorders
likely proband denied a family history of eating
disorders, or refused permission to contact
possibly ill relatives, the screening was
terminated. Otherwise, a preliminary verification
of the diagnosis of AN was undertaken and
eating disorder histories on possibly affected
relatives were obtained. If probands met all
inclusion and no exclusion criteria, and gave a
history suggestive of eating disorder in a nonparent, non-child, and a non-MZ twin blood
relative, the proband was asked to discuss the
study with the affected relative and obtain
permission for study personnel to contact the
relative for informed consent. Study personnel
then contacted the relative who was screened for
eligibility. If the relative fulfilled entrance criteria, both the proband and affected relative
were scheduled for the complete battery of
evaluative procedures. At the time that the
interviews were scheduled, the proband and
affected relative were told that they would be
mailed a packet of self-rating assessments. They
were asked to complete the assessments and
bring the packet to the interview. For those
probands and relatives who were not able to
come to a satellite centre for an in-person
interview, the interview was conducted by
telephone and the self-rating assessments were
returned by mail. Only AN probands and
siblings with AN and BN diagnoses are reported
in the current study due to reasons described in
the ‘ Participants ’ section.
Data analysis
Data analysis was conducted in several stages.
An initial principal components factor analysis
applying a varimax rotation was performed on
individual TCI scales to evaluate whether the
factor structure would be replicated with our
eating disorder sample.
Next, to characterize the personality and
behavioural attributes of individuals with eating
disorders, we performed an exploratory factor
analysis with varimax rotation using the
responses of our study participants to the
following personality and behavioural assessments : the seven TCI scales, two measures of
obsessive–compulsive symptoms (Y-BOCS and
YBC-EDS), a multidimensional measure of
perfectionism (MPS), and a measure of trait
anxiety (STAI).
The initial factor analysis grouped data for all
639
sites (or populations). To determine whether
there was heterogeneity among populations, a
delete-one jackknife procedure was done. This
evaluated the results of the factor analysis after
deleting one population at a time. Any population that was an ‘ outlier ’, as determined by the
jackknife analysis, was deleted from the sample
and the initial factor analysis was repeated. To
explore further potential differences among
populations, a factor analysis was performed on
data from the three populations with the largest
sample sizes (excluding any ‘ outliers ’).
To evaluate whether the personality\
behavioural constructs extracted from the factor
analysis were useful for predicting eating disorder subdiagnoses, a discriminant analysis was
performed using the factors and the four
diagnostic subclassifications : anorexia nervosarestricting type (AN-R), anorexia nervosa-purging type (AN-P), anorexia nervosa-bingeing or
bingeing and purging type (AN-B), and BN.
Discriminant analysis is a statistical method that
utilizes trait attributes to discriminate members
of two or more groups from one another. That
is, this analytical approach allows one to predict
the group membership status of subjects based
upon their scores on quantitative trait attributes.
Our methods follow classic discriminant analysis
procedures as implemented in S-Plus (Venables
& Ripley, 1994). First, using a random selection
of 80 % of the data (the training set), a
classification tree was built based on factors 1–4
from the factor analysis. The tree itself is based
on bifurcating factor splits that yield optimal
separation of populations into diagnostic
categories. Using the remaining 20 % of the data
as the test set, the tree built with the training set
is pruned to provide a more accurate classification tree. The accuracy is improved by
avoiding overfitting the training data. All data
analyses were performed using the SAS statistical package (version 6.12)
RESULTS
Factor analysis of the TCI with an eating
disordered sample
Factor loadings for each individual scale were
similar and positive, confirming the TCI factor
structure for our eating disorder sample. In
addition, the fraction of variance explained by
the first factor was substantial for all scales.
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The Price Foundation Collaborative Group
Table 1. Raw scores on the personality and behavioural measures across all sites
Variables
YBC-EDS
Y-BOCS
MPS
STAI-T
NS
HA
RD
PS
SD
C
ST
Munich
(N l 78)
New York
(N l 65)
Pittsburgh
(N l 59)
Toronto
(N l 52)
Los Angeles
(N l 48)
London
(N l 37)
Philadelphia
(N l 9)
21n55
(6n53)
8n57
(10n70)
84n71
(23n97)
50n32
(12n35)
18n88
(7n20)
20n66
(8n52)
15n72
(3n86)
4n76
(2n11)
22n13
(8n96)
29n45
(5n57)
13n62
(6n41)
25n23
(5n59)
15n88
(11n84)
95n86
(21n06)
52n63
(14n10)
19n53
(7n00)
21n56
(7n79)
16n90
(3n84)
5n80
(2n28)
24n50
(9n40)
32n85
(6n51)
13n74
(6n52)
25n07
(4n66)
17n88
(10n89)
101n63
(21n68)
50n50
(14n24)
15n55
(7n07)
20n47
(7n91)
17n33
(3n97)
6n76
(1n71)
28n48
(9n75)
35n24
(6n30)
16n01
(7n00)
26n51
(7n53)
18n78
(13n50)
104n94
(23n61)
55n61
(15n92)
16n37
(7n74)
23n40
(8n09)
16n37
(3n96)
6n11
(1n96)
25n74
(9n59)
34n08
(7n24)
15n87
(7n61)
23n54
(5n52)
17n69
(10n46)
102n74
(20n44)
53n95
(13n25)
18n04
(7n57)
22n11
(7n57)
15n89
(4n50)
5n72
(2n22)
25n81
(9n54)
31n66
(6n93)
14n04
(6n41)
25n46
(5n74)
12n38
(12n31)
101n86
(18n50)
53n59
(13n01)
14n53
(7n80)
22n97
(7n28)
16n69
(3n50)
6n38
(1n99)
24n23
(7n60)
33n89
(5n98)
13n09
(6n46)
25n78
(5n64)
17n25
(11n02)
106n27
(27n15)
49n75
(16n60)
20n22
(7n10)
19n79
(9n09)
18n21
(3n71)
6n22
(1n32)
24n36
(9n44)
30n04
(9n46)
18n00
(9n27)
Values are means (standard deviations).
YBC-EDS, Lifetime worst total score from the Yale–Brown–Cornell-Eating Disorder Scale.
Y-BOCS, Lifetime worst total score from the Yale–Brown-Obsessive–Compulsive Scale.
MPS, Lifetime worst total score from the Multidimensional Perfectionism Scale.
STAI-T, Trait Anxiety from the State-Trait Anxiety Inventory.
Temperament and Character Inventory (TCI) scales : NS, Novelty Seeking ; HA, Harm Avoidance ; RD, Reward Dependence ; PS,
Persistence ; SD, Self-Directedness ; C, Cooperativeness ; ST, Self-Transcendence.
Thus, we had confidence in using the seven
temperament and character scales for the remaining analyses.
Factor analysis of personality and behavioural
measures
The jackknife analysis revealed one highlyinfluential population, Munich, which differed
from other sites with regard to the personality
and behavioural traits of their subjects. In
viewing Table 1, it is clear that the primary
discrepancy between Munich and the other sites
is substantially lower Y-BOCS scores, as well as
lower YBC-EDS and MPS scores compared to
all other sites. Due to the undetermined reason
for this significant site difference, we excluded
Munich from the remaining factor analyses.
The results of the factor analysis are presented
in Table 2. The first four factors explained 51 %
of the variance in the personality and
behavioural traits, with factors 1–4 accounting
for 14, 13, 13 and 11 % of the variance
respectively. The weightings for factor 1 reflect a
classic profile of eating disordered individuals,
which includes moderate to strong positive
loadings on trait anxiety (STAI-T), harm avoidance (HA), perfectionism (MPS), general and
eating-specific obsessive–compulsive symptoms
(YBOCS ; YBC-EDS). An additional strong
negative loading on this factor was found for
self-directedness (SD). Factor 2 reveals ties
between reward dependence (RD) and cooperativeness (C), with weaker links to SD and
lack of anxiety (STAI-T). Factor 3 reveals a
connection between perfectionism (MPS), persistence (PS), and self-transcendence (ST), with
some weaker associations with general (YBOCS) and eating-specific obsessive–compulsive
behaviours (YBC-EDS). Factor 4’s weightings
are dominated by novelty-seeking (NS).
To explore differences among populations, a
factor analysis was performed on data from the
three North American sites with the largest
sample sizes. Because a 5 : 1 ratio of subjects to
variables is recommended for factor analysis
(Bryant & Yarnold, 1998), data from the Los
Angeles, London and Philadelphia sites were
not factor analysed individually due to their
641
Deriving behavioural phenotypes of eating disorders
relatively small individual sample sizes. Data
from the Munich site were not factor analysed
individually due to the undetermined reason for
substantial differences on several assessment
measures compared to all other sites. Only the
weightings for the first factor are reported (Table
3), although four factors were extracted from
the data. The first factor explains 23, 26 and
29 % of the variance for the data from the New
York (N l 65), Pittsburgh (N l 59), and
Toronto (N l 52) populations respectively. For
individuals from New York, the construct is
specifically characterized by high loadings
on STAI-T and HA. For individuals from
Pittsburgh and Toronto, the construct encompasses a wider range of characteristics, including
HA, STAI-T, MPS and obsessive–compulsive
symptoms (general and eating-related) (Y-BOCS
and YBC-EDS). Diminished SD is also strongly
tied to this anxious–obsessional construct for
each of these three sites.
Discriminant analysis
Discriminant analysis was used to evaluate the
extent to which we can accurately classify
Table 2. Factor analysis of personality and
behavioural measures for individuals diagnosed
with eating disorders (N l 270) (excluding the
sample from Munich)
Factor
Variable
YBC-EDS
Y-BOCS
MPS
STAI-T
NS
HA
RD
PS
SD
C
ST
1
2
3
4
0n454
0n486
0n531
0n806
k0n187
0n780
*
*
k0n773
k0n210
*
*
*
*
k0n197
*
*
0n692
*
0n325
0n697
0n155
0n294
0n274
0n508
*
k0n201
k0n187
*
0n594
0n212
0n186
0n434
*
*
*
*
0n722
k0n383
0n152
k0n204
*
k0n149
0n356
YBC-EDS, Lifetime worst total score from the Yale–Brown–
Cornell-Eating Disorder Scale.
Y-BOCS, Lifetime worst total score from the Yale–BrownObsessive–Compulsive Scale.
MPS, Lifetime worst total score from the Multidimensional
Perfectionism Scale.
STAI-T, Trait Anxiety from the State-Trait Anxiety Inventory.
Temperament and Character Inventory (TCI) scales : NS, Novelty
Seeking ; HA, Harm Avoidance ; RD, Reward Dependence ; PS,
Persistence ; SD, Self-Directedness ; C, Cooperativeness ; ST, SelfTranscendence.
* Factor loading was 0.
Table 3. Factor analyses for the three North
American recruitment sites with the largest
sample sizes. Only the first factor loadings are
presented
Sites
% Variance explained
YBC-EDS
Y-BOCS
MPS
STAI-T
NS
HA
RD
PS
SD
C
ST
New York
(N l 65)
23 %
Pittsburgh
(N l 59)
26 %
Toronto
(N l 52)
29 %
0n277
0n395
0n368
0n830
k0n146
0n827
*
k0n213
k0n771
k0n227
0n168
0n558
0n471
0n659
0n728
k0n236
0n758
*
*
k0n844
*
0n141
0n541
0n645
0n660
0n830
*
0n655
k0n119
0n259
k0n807
k0n326
0n163
YBC-EDS, Lifetime worst total score from the Yale–Brown–
Cornell-Eating Disorder Scale.
Y-BOCS, Lifetime worst total score from the Yale–BrownObsessive–Compulsive Scale.
MPS, Lifetime worst total score from the Multidimensional
Perfectionism Scale.
STAI-T, Trait Anxiety from the State-Trait Anxiety Inventory.
Temperament and Character Inventory (TCI) scales : NS, Novelty
Seeking ; HA, Harm Avoidance ; RD, Reward Dependence ; PS,
Persistence ; SD, Self-Directedness ; C, Cooperativeness ; ST, SelfTranscendence.
* Factor loading was 0.
subjects into diagnostic subgroups using only
the extracted personality\behavioural factors.
The degree to which these factors can accurately
‘ sort ’ our subjects has direct implications for
using these traits to define a useful behavioural
phenotype. To evaluate whether the factors were
indeed useful for predicting subdiagnosis, discriminant analysis was performed using the
factors and the four diagnostic subclassifications : AN-R, AN-P, AN-B and BN.
Discrimination into the four diagnostic subcategories based upon the personality\
behavioural factors yielded an overall misclassification rate of 33n8 %. The misclassification varied by subdiagnosis (Table 4 A), with a
strong trend toward increasingly accurate classification of subjects with AN-R. That is, most
AN-R subjects (80 %), but only slightly more
than half of all other subjects, were classified
into the correct diagnostic subtype based upon
the personality\behavioural factors. However,
this presentation does not give the full picture.
Another way to view the data is to ask : ‘ Given
642
The Price Foundation Collaborative Group
Table 4. Discriminant analysis into four diagnostic subcategories using the
personality\behavioural trait factors from Table 2
A
Percentage of subjects with a given subdiagnosis who were correctly labelled as having that
subdiagnosis
Actual subdiagnosis
Correctly classified
(true positive)
%
Incorrectly classified
(false negative)
%
80n0
52n0
49n0
57n6
20n0*
48n0
51n0
42n8
Restricting anorexia nervosa
Purging anorexia nervosa
Bingeing anorexia nervosa
Bulimia nervosa
* These subjects were incorrectly labelled with some subdiagnosis other than their true subdiagnosis of restricting anorexia nervosa when
classified using the personality\behavioural factors.
B Percentage of subjects labelled as having a given subdiagnosis who actually have that
subdiagnosis
‘ Subdiagnosis ’ based upon
personality\behavioural factors
Correctly classified
(true positive)
%
Incorrectly classified
(false positive)
%
68n9
64n6
60n0
47n5
31n1†
35n4
40n0
52n5
Restricting anorexia nervosa
Purging anorexia nervosa
Bingeing anorexia nervosa
Bulimia nervosa
† The actual subdiagnosis of these subjects is something other than restricting anorexia nervosa.
‘ Bingeing anorexia nervosa ’ includes those anorexic subjects with bingeing only and those with bingeing and purging symptomatology ;
‘ Purging anorexia nervosa ’ includes those anorexic subjects with purging, but no history of bingeing.
the assigned ‘‘ subdiagnosis ’’ based upon the
personality\behavioural factors, what fraction
of individuals actually have that subdiagnosis ? ’.
By this view, the discriminant analysis was
successful approximately two-thirds of the time
for all AN subdiagnoses, but slightly less than
half the time for a BN diagnosis (Table 4 B).
DISCUSSION
Phenotypic characterization
Factor analysis revealed that the strongest factor
underlying the cluster of personality and
behavioural traits in this sample is a combination
of trait anxiety, harm avoidance, perfectionism, obsessive–compulsive behaviour, and
diminished self-directedness. Importantly, the
current study raises the possibility that these five
traits may be best conceptualized as parts of the
same underlying construct among individuals
with AN and related eating disorders. This
primary factor supports past research (Casper,
1990 ; Brewerton et al. 1993 ; Kleifield et al.
1993 ; Kaye et al. 1993 ; Waller et al. 1993 ; Bulik
et al. 1995 a, b ; 1997 a ; Srinivasagam et al. 1995 ;
Joiner et al. 1997 ; Fairbum et al. 1997 ; Pollice et
al. 1997 ; Kaye et al. 1998 ; Lilenfeld et al. 1998,
2000) demonstrating anxiety, harm avoidance,
perfectionism and obsessive–compulsive behaviour to be potential vulnerability factors for the
development of eating disorders, AN in particular.
Of all five traits, self-directedness has been the
least studied. The central elements of selfdirectedness are the acceptance of responsibility
for one’s own choices, identification of individually valued goals and purposes, development
of skills and confidence in solving problems, and
self-acceptance (Cloninger et al. 1993). Therefore, low levels of self-directedness may be
conceptualized as immaturity, ineffectiveness,
and lacking an integrated view of oneself. Low
self-directedness has recently been demonstrated
to be a reasonably good predictor of personality
disorder (Bulik et al. 1995 b) and high selfdirectedness has been found to predict rapid and
sustained treatment response (Bulik et al. 1999)
in a bulimic sample.
Deriving behavioural phenotypes of eating disorders
Several differences emerged across subjects
from different parts of the world when sites were
compared. For those individuals from New
York, the primary personality factor was best
characterized by trait anxiety, harm avoidance
and diminished self-directedness. In addition to
these three traits, for those from Pittsburgh and
Toronto, the factor also encompassed perfectionism and obsessive–compulsive behaviour.
Notably, the Munich sample differed from the
other sites. There are at least two possible
explanations for this difference. There could
be cultural differences in the personality\
behavioural constructs that characterize individuals with eating disorders from Munich
compared with those from other parts of the
world. Such differences may suggest the importance of cultural influences in the development of eating disorders and related personality characteristics. Alternatively, the
differences could be due to translation of the
assessment instruments, as Munich was the only
non-English speaking site. Overall however,
there were more similarities than differences
across sites.
Classification
Our first question was : ‘ How often are subjects
assigned the correct subdiagnostic label, based
solely upon the personality\behavioural
factors ? ’. Results of the discriminant analysis
revealed that on average, subjects were accurately classified into the proper diagnostic
subtype category based solely upon the extracted
personality\behavioural factors approximately
two-thirds of the time. However, we were much
more accurate (i.e. 80 % accuracy) in classifying
subjects with restricting-type anorexia nervosa
into the appropriate category than any other
eating disorder subtype.
Our second question was : ‘ Of all those
subjects ‘‘ labelled ’’ as belonging to a particular
diagnostic subgroup based solely upon the
personality\behavioural factors, how many actually have that diagnosis ? ’. Comparable diagnostic accuracy was demonstrated across all
anorexic subgroups, whereas there was substantially less accuracy in classifying subjects as
having bulimia nervosa. That is, more than half
of subjects who were classified as bulimic based
upon the personality\behavioural factors, were
actually anorexic.
643
One possible reason that there was more
accuracy in classifying subjects with restrictingtype AN is because they have a more homogeneous phenotype. Our findings support the
frequent observation that these individuals
have a remarkably consistent personality and
behavioural presentation (Sohlberg & Strober,
1994). If the restricting anorexic subtype indeed
has the clearest phenotypic characterization,
this subset of individuals may be the most
promising focus for future genetic work.
Subtype misclassification may be partly
explained by the fact that a significant minority
of individuals with AN later develop BN (e.g.
Eckert et al. 1995 ; Bulik et al. 1997 b ; Strober et
al. 1997). However, if this ‘ conversion ’ is to take
place, it most often occurs within 3 to 5 years
after the onset of AN. This is precisely why we
required restricting-type AN probands to have a
‘ pure ’ diagnosis ; that is, the onset of their illness
must have been at least 3 years prior to
ascertainment, with no prior or subsequent
history of bulimic behaviour. However, a similar
‘ purity ’ criterion was not applied to affected
relatives ; that is, they simply needed to meet
DSM-IV criteria in order to receive a diagnosis
of restricting-type AN. Therefore, some subtype
misclassification may be explained by ‘ impure ’
diagnostic categories, consisting partially of
relatives classified as AN-R who may later go on
to develop BN.
Caveats
Inference for this study is restricted to a
population of individuals with eating disorders.
This population is commonly characterized by
extreme values on personality and behavioural
measures. Therefore, the relationships among
these measures cannot be taken as representative
of the general population. In addition, the nature
of the current sample is very selective (i.e.
anorexic probands and their eating disordered
siblings). Therefore, we also may not be able to
generalize our findings to all individuals with
eating disorders. Next, the current study lacks a
comparison group, such as a random sample
from the population. A comparison sample
would undoubtedly magnify the similarities
among individuals with eating disorders, who
tend to score more extremely on these personality
and behavioural measures than would
randomly-chosen individuals from the popu-
644
The Price Foundation Collaborative Group
lation. Finally, our findings should be replicated
on an independent sample.
Conclusions
The current findings suggest that the phenotypic
characterization of eating disorders may be
enriched for genetic studies by the inclusion of
empirically derived personality and behavioural
constructs. An important implication of the
current findings is that trait anxiety, harm
avoidance, perfectionism, obsessive–compulsive
behaviour, and diminished self-directedness may
constitute a single underlying construct among
individuals with AN and related eating disorders.
These data are consistent with a substantial
literature showing that anorexic individuals have
extreme levels of behavioural rigidity, emotional
restraint and perfectionism.
The phenotypic variables assessed in this
cohort may prove useful in elucidating the
genetic susceptibility to disease in several ways.
For example, analysis of genotypic data on pairs
of affected relatives by allele-sharing methods
can include quantitative covariates, such
that pairs of relatives characterized by high
trait anxiety, harm avoidance, perfectionism, obsessive–compulsive behaviour, and
diminished self-directedness scores are given
greater weight than pairs without this profile.
This may allow for the definition of more
genetically homogeneous subgroups among the
cohort, facilitating the detection of loci whose
action to increase risk for AN is more
pronounced on the background of these
personality\behavioural traits. We are hopeful
that this effort to identify quantitative traits will
offer enhanced power to search for accompanying genotypes that contribute to the pathophysiology of eating disorders.
This work was financially supported by the Price
Foundation of Geneva, Switzerland.
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