Anorexia nervosa trios: behavioral profiles of
individuals with anorexia nervosa and their parents
M. J. Jacobs*, S. Roesch, S. A. Wonderlich, R. Crosby, L. Thornton, D. E. Wilfley, W. H. Berrettini,
H. Brandt, S. Crawford, M. M. Fichter, K. A. Halmi, C. Johnson, A. S. Kaplan, M. LaVia, J. E. Mitchell,
A. Rotondo, M. Strober, D. B. Woodside, W. H. Kaye and C. M. Bulik
University of California, San Diego (UCSD) Eating Disorders Treatment and Research Center, La Jolla, CA, USA
Background. Anorexia nervosa (AN) is associated with behavioral traits that predate the onset of AN and persist
after recovery. We identified patterns of behavioral traits in AN trios (proband plus two biological parents).
Method. A total of 433 complete trios were collected in the Price Foundation Genetic Study of AN using
standardized instruments for eating disorder (ED) symptoms, anxiety, perfectionism, and temperament. We used
latent profile analysis and ANOVA to identify and validate patterns of behavioral traits.
Results. We distinguished three classes with medium to large effect sizes by mothers’ and probands’ drive for
thinness, body dissatisfaction, perfectionism, neuroticism, trait anxiety, and harm avoidance. Fathers did not differ
significantly across classes. Classes were distinguished by degree of symptomatology rather than qualitative
differences. Class 1 (y33%) comprised low symptom probands and mothers with scores in the healthy range. Class 2
(y43%) included probands with marked elevations in drive for thinness, body dissatisfaction, neuroticism, trait
anxiety, and harm avoidance and mothers with mild anxious/perfectionistic traits. Class 3 (y24%) included
probands and mothers with elevations on ED and anxious/perfectionistic traits. Mother–daughter symptom severity
was related in classes 1 and 3 only. Trio profiles did not differ significantly by proband clinical status or subtype.
Conclusions. A key finding is the importance of mother and daughter traits in the identification of temperament and
personality patterns in families affected by AN. Mother–daughter pairs with severe ED and anxious/perfectionistic
traits may represent a more homogeneous and familial variant of AN that could be of value in genetic studies.
Received 11 July 2007; Revised 9 May 2008; Accepted 14 May 2008; First published online 26 June 2008
Key words: Anorexia nervosa, eating disorder, genetics, temperament.
A growing body of genetic research has associated
anorexia nervosa (AN) with a cluster of behavioral
traits that appear to predate onset of the disorder and
persist following recovery (Fairburn et al. 1999; Price
Foundation Collaborative Group, 2001; Devlin et al.
2002; Kaye et al. 2003; Agras et al. 2004). These traits,
which include perfectionism, anxiety and harm
avoidance, may be susceptibility traits for developing
AN and may also contribute to chronicity of illness
and high relapse rates. In addition, these traits are
heritable and occur in family members of individuals
with AN (Jonnal et al. 2000; Kaye et al. 2004b; Tozzi
et al. 2004). This is the first study to examine the pat-
terns of behavioral traits in a large, carefully screened
sample of AN probands and both of their biological
The panel of traits chosen for this study comprises
perfectionism, anxiety, and temperamental features,
including novelty seeking and harm avoidance.
Perfectionism has been identified as a potential risk
factor for the development of AN (Fairburn et al. 1999;
Halmi et al. 2000). Mothers of individuals with AN
have shown evidence of elevated levels of perfection-
ism and drive for thinness relative to gender- and age-
matched controls (Woodside et al. 2002). Anxiety has
also been identified as a risk factor for AN. Anxiety
disorders are more prevalent among individuals
with AN than normal controls (Deep et al. 1995;
Bulik et al. 1997; Kaye et al. 2004a). Evidence suggests
that anxious personality traits predate onset of AN
and persist following recovery (Kaye et al. 2003).
Individuals with AN often demonstrate low levels of
novelty seeking and high levels of harm avoidance
* Address for correspondence: M. J. Jacobs, Ph.D., UCSD Eating
Disorders Treatment and Research Center, 8950 Villa La Jolla, C-207,
La Jolla, CA 92037, USA.
Portions of this paper were presented at the annual meeting of the
Eating Disorders Research Society, Toronto, Canada, 29 September–
2 October 2005.
Psychological Medicine (2009), 39, 451–461.
f 2008 Cambridge University Press
Printed in the United Kingdom
relative to controls (Fassino et al. 2002; Karwautz et al.
The personality characteristics described above
may be present to a significant degree in AN families
and create a temperamental susceptibility for AN
(Sohlberg & Strober, 1994). Efforts to define eating
disorder (ED) phenotypes empirically have motivated
analyses based on behavioral traits rather than strictly
diagnostic criteria (Goldner et al. 1999; Bulik et al. 2000,
2007; Westen & Harnden-Fischer, 2001; Keel et al.
2004). Although the literature suggests that differences
in underlying behavioral traits may influence AN
subtypes (i.e. restricting versus binge eating/purging),
the precise nature of that relationship remains unclear
(Herzog et al. 1996; Eddy et al. 2002; Ward et al. 2003;
Vervaet et al. 2004). More recent longitudinal studies
suggest that some of the previously identified differ-
ences between subtypes may reflect methodological
issues (e.g. length of follow-up, sample size) rather
than clear phenotypic differences (Herzog et al. 1996;
Eddy et al. 2002). These methodological issues have
clouded efforts to provide more definitive conclusions
regarding the significance and/or appropriateness of
the current taxonomy of AN (Herzog et al. 1996; Agras
et al. 2004).
The primary aim of the present study was to
identify cross-generational clusters of behavioral traits
occurring among a large, rigorously screened sample
of AN probands and their parents. We sought to
characterize behavioral profiles of AN trios that could
facilitate the identification of homogeneous and fam-
ilial subtypes of AN that could be useful in genetic
research. This is the first Price Foundation study to
undertake such examination of parent–child trios.
Our secondary aim included a validation of latent
classes by comparing probands across latent classes on
personality, clinical status, and ED subtype.
Participants and study design
The sample for this analysis comprised individuals
and parents enrolled in the multi-site International
Price Foundation Study of the Genetics of Anorexia
Nervosa (Kaye et al. 2000). This study is part of an
effort to identify susceptibility loci for EDs. The
sample of the present study includes 433 complete AN
trios (proband plus two biological parents). An ad-
ditional 88 probands had one participating parent;
only probands with both participating parents were
included in the trio analyses. In addition, because of
the small number of males recruited into the study
(n=12), only trios with female probands were in-
cluded in the analyses. Participants with a history of
AN were recruited from nine sites in Europe and
the USA, including: Pisa, Italy; Munich, Germany;
New York, NY; Los Angeles, CA; Baltimore, MD; and
Tulsa, OK, USA. Each participating site obtained
approval from its local Institutional Review Board;
all participants gave written informed consent to par-
ticipate in the study.
Acceptance into the study did not require active
illness at the time of assessment and was not restricted
by sex of the proband. Current use of medication did
not affect the eligibility of probands (Kaye et al. 2004b).
Probands entered into the study met the following
criteria: (1) had an unequivocal lifetime diagnosis
of AN [meeting modified DSM-IV criteria for AN
(APA, 1994), excluding amenorrhea] at least 3 years
prior to entry into the study; (2) low weight must
have been less than the fifth percentile of body mass
index (BMI) for age and gender on the Hebebrand
(1996) chart of the National Health and Nutrition
sample (Hebebrand et al. 1996); (3) had an age of onset
prior to age 25; (4) were Caucasian; and (5) were
between the ages of 13 and 65 years. Subtypes were
defined in the following manner: (1) restricting only
(RAN), (2) purging with no binge eating (PAN), and
(3) bingeing-purging subtype (BAN), which included
individuals with binge eating with or without purg-
ing. The AN diagnosis is a lifetime diagnosis of AN
and does not take into consideration other ED diag-
noses. Probands could be currently ill or in remission
at the time of study entry. Exclusionary criteria in-
cluded onset of AN after age 25 or a lifetime history of
any of the following: dementia; schizophrenia; mental
retardation; organic brain syndrome; bipolar I or bi-
polar II, if symptoms of AN occurred only in the con-
text of a manic or hypomanic episode; intelligence
quotient (IQ) <70; maximum BMI since puberty >27
for females and >27.8 for males; medical condition
affecting body weight, appetite, or eating behavior (i.e.
individuals with diabetes and thyroid conditions were
excluded if the onset of the disease preceded the onset
of the ED). Parents of probands were invited to par-
ticipate, regardless of age, medication status or psy-
chiatric diagnosis. Parental participation was optional.
The assessment battery for this study was selected to
facilitate ED diagnoses and to assess psychological
and personality features that are known to be
heritable and relevant to ED vulnerability. ED diag-
noses and symptom profiles of probands were ob-
tained using the Structured Inventory of Anorexia
Nervosa and Bulimic Syndromes (SIAB; Fichter et al.
452 M. J. Jacobs et al.
1998) and the expanded version of Module H of
the Structured Clinical Interview of DSM-IV Axis I
Disorders (SCID-I; First et al. 1996). The SIAB is a semi-
structured clinical interview designed to obtain a
detailed eating and weight history and to establish a
DSM-IV ED diagnosis. ED recovery status and the
presence or absence of ED behaviors (i.e. bingeing,
purging) were obtained using the expanded version of
Module H of SCID-I.
ED symptomatology of probands and parents
was assessed using the Eating Disorder Inventory-2
(EDI-2; Garner, 1990), which is a 91-item questionnaire
consisting of 11 subscales that assess specific cognitive
and behavioral ED dimensions. The subscales in-
cluded in the present study include the bulimia, drive
for thinness, and body dissatisfaction subscales.
The original version of the EDI (Garner et al. 1983)
demonstrated good internal consistency, convergent
and discriminant validity. The EDI has been widely
used in ED research and is reported to successfully
discriminate between subjects with and without
EDs (Garner et al. 1983). The three subscales in the
present study were chosen for their utility in assessing
domains of primary interest.
Obsessions and compulsions of probands were
assessed using the Yale–Brown Obsessive Compulsive
Scale (YBOCS; Goodman et al. 1989) and the Yale–
Brown–Cornell Eating Disorder Scale (YBC-EDS;
Sunday et al. 1995). The YBOCS is a semi-structured
interview designed to assess the presence and severity
of obsessive thoughts and compulsive behaviors. It
has excellent inter-rater reliability and is considered to
be the ‘gold standard’ for measuring OC symptom
severity (Pato et al. 1994). The YBC-EDS is similar to
the YBOCS, but assesses core obsessions and compul-
sions specific to EDs. The YBC-EDS has demonstrated
excellent inter-rater reliability, internal consistency
and convergent validity (Mazure et al. 1994).
assessed using the Multidimensional Perfectionism
Scale (MPS; Frost et al. 1990). The MPS is a 35-item
factor-analytically developed questionnaire designed
to evaluate overall perfectionism as well as six specific
dimensions of perfectionism (including high personal
standards, concern over mistakes, high perceived
parental criticism, high perceived parental expecta-
tions, doubt about quality of performance, and need
for organization, order, and precision). Internal con-
sistency coefficients for the factor scales range from
0.77 to 0.93. The reliability of the overall perfectionism
scale is 0.9 (Frost et al. 1990). The MPS has been shown
to successfully discriminate between individuals with
and without EDs (Srinivasagam et al. 1995). Supported
by findings from Tozzi et al. (2004), the current study
proceeded from the notion that perfectionism is a
multi-dimensional construct. We used the MPS
total score to best capture this multi-dimensionality.
The Temperament and Character Inventory (TCI;
Cloninger et al. 1993) was used to assess temperament
in probands and parents. The TCI is a 240-item factor-
analytically developed questionnaire measuring seven
personality dimensions: four dimensions relate to
temperament and three relate to character. The tem-
perament dimensions include novelty-seeking, harm
avoidance, reward dependence, and persistence.
The character dimensions include self-directedness,
cooperativeness, and self-transcendence. The TCI
demonstrates acceptable internal consistency, ranging
from 0.76 to 0.89 (Cloninger et al. 1994).
Neuroticism in probands and parents was mea-
sured using the Revised Neuroticism–Extroversion–
Openness Personality Inventory (NEO PI-R; Costa
& McCrae, 1992), which is a 240-item questionnaire
that evaluatesfive major
(neuroticism, extraversion, openness to experience,
agreeableness, and conscientiousness), based on the
Five-Factor Model of personality. The subscale of
interest in the present study was neuroticism, which
is deemed to be a marker of psychopathology and
psychological distress (Ormel et al. 2004). The neuro-
ticism scale of the NEO PI-R measures the following
six facets of the construct: anxiety, depression, angry
hostility, impulsivity, self-consciousness, and vulner-
Impulsivity in probands and parents was assessed
with the Barratt Impulsivity Scale-11 (BIS-11; Barratt,
1983), which is a 30-item self-report measure of
impulsiveness. The BIS measures three aspects of im-
pulsiveness: cognitive, motor, and non-planning. This
measure has been shown to successfully discriminate
the degree of impulse control in subgroups of women
with eating disorders (Bulik et al. 1997).
assessing using the Spielberger State-Trait Anxiety
Inventory (STAI; Spielberger et al. 1970), which is a
widely used 40-item questionnaire that assesses cur-
rent anxiety (state) and general levels of anxiety (trait).
The questionnaire asks participants to report ‘how
they feel at this moment’ and how they ‘generally
feel’. State and trait assessments with this measure
demonstrate high internal consistency, ranging from
0.86 to 0.96.
Latent profile analysis (LPA)
LPA was conducted to identify latent classes of trios
with similar temperament and personality patterns.
The rationale for using LPA in the present study was
to use an empirically driven approach in defining
AN trios 453
clusters of trios based on behavioral traits. LPA was
performed using MPlus version 3.0 (Muthen &
Muthen, 2004). The primary goals of LPA are to (a)
identify the number of classes or groups that best
represent the data (i.e. overall model fit) and (b) to
substantively identify the classes. Model fit in the
current study was determined using both the Vuong–
Lo–Mendell–Rubin (VLMR) Likelihood Ratio test and
the size-adjusted Bayesian information criteria (ABIC).
The VLMR is a statistical test that compares a target
class solution (e.g. 3) to a class solution that is fit with
one fewer class (e.g. 2). A statistically significant result
(i.e. p<0.05) indicates that the higher class solution
better represents the data. Once overall model fit is
determined, substantive identification of classes is
undertaken. To describe each class, the conditional
response means for each indicator variable are evalu-
ated. Each family member is treated as an indepen-
dent entity in the analysis. All indicator variables were
treated as conditionally independent.
The necessity of including data from three groups of
participants, the large number of potential variables,
and the limits on the number of variables that could
meaningfully be examined in the LPA necessitated a
parsimonious approach in choosing variables for in-
clusion. The variables included were those that have
consistently demonstrated a relationship to the onset
and maintenance of AN. To maximize the use of
available data, key variables from several measures
were chosen. As noted above, there is substantial
support for the role of perfectionism, trait anxiety,
harm avoidance, and neuroticism in AN, as well as
drive for thinness and body dissatisfaction. Thus,
these variables were chosen for inclusion in the trio
analysis. The nature of LPA, which separates the three
groups that have little within-group variability, ob-
viated the need to include age as a covariate. Indicator
variables included in the LPAs were the following:
EDI drive for thinness and body dissatisfaction sub-
scales; MPS total perfectionism score; NEO neuroti-
cism subscale; STAI trait anxiety subscale; and TCI
harm avoidance subscale.
To characterize the clusters, univariate ANOVA was
conducted for the best-fitting class solution; ANOVA
was used to identify significant differences between
groups. Within-class differences were investigated
using paired-sample t tests. External validation of the
results of the LPAs was conducted to investigate
whether classes derived from the LPAs demonstrated
other clinically meaningful differences. Univariate
ANOVA (with post-hoc comparisons) and x2tests were
used. Variables included in the external validation
procedure included the following: EDI bulimia
subscale; BIS motor, non-planning, and cognitive
subscales; STAI state anxiety subscale; TCI novelty
seeking and self-directedness subscales; YBC-EDS
current total score (probands only); and YBOCS total
score (probands only). The rationale for inclusion of
these variables was based on a review of the litera-
ture establishing the relevance of these variables to
domains being measured by the LPAs, including ED
symptoms and characteristics related to temperament,
anxiety and OC symptoms.
Because of the large number of comparisons, sample
size and exploratory nature of many analyses included
in this study, a conservative per comparison a-level of
0.001 was used to control for Type I error. Measures of
effect size were also included.
Behavioral traits and demographic characteristics of
participants in the present study are presented in
Tables 1 and 2.
LPA indicated three distinct classes of families. The
three-class solution had a VLMR significance level
of p=0.01, indicating that the three-class solution was
superior to a two-class solution; the three-class sol-
ution was also superior to a more complex, four-class
solution. The ABIC for the three-class solution was
47365.9. In combination, the VLMR and the ABIC
suggest that the three-class solution best fit the
data. One class, constituting approximately 33% of
Table 1. Proband demographic information for AN probands
Age of onset, mean (S.D.)
Age of first ED symptom, mean (S.D.)
Clinical status (past month), n (%)
Purging only (PAN)
BMI (kg/m2), mean (S.D.)
AN, Anorexia nervosa; S.D., standard deviation;
ED, eating disorder; BMI, body mass index.
454 M. J. Jacobs et al.
the sample, reported less extreme scores than classes 2
(y43% of the sample) and 3 (y24% of the sample) on
the vast majority of variables that significantly differed
between classes (see Tables 3 and 4). The three classes
will be referred to using the following labels: mod-
erate symptomatology probands/healthy mothers
(class 1), highest symptomatology probands/moder-
ate symptomatology mothers (class 2), and high
mothers (class 3). Fathers in the three classes did not
differ significantly on any of the variables tested.
One-way ANOVA was conducted for each variable
that differed significantly between classes of families,
followed by pairwise comparisons to further explore
significant differences between groups. Detailed find-
ings for each subgroup and variable investigated are
available in the accompanying tables (Tables 3 and 4).
Class 1 was characterized by probands with moderate
levels of symptoms compared to the other probands
and low symptom mothers. With the exception of
maternal perfectionism, this group reported the lowest
levels of both proband and mother drive for thinness,
body dissatisfaction, neuroticism, trait anxiety, harm
avoidance, and proband perfectionism.
For the most part, class 2 was characterized by the
highest levels of symptoms among probands and
mothers with moderate symptoms relative to mothers
in the other two classes. Finally, class 3 was charac-
terized by having both probands and mothers with
high levels of symptoms relative to the other classes on
many of the variables investigated. More specifically,
the mothers in this class had the highest levels of
drive for thinness, body dissatisfaction, perfectionism,
neuroticism, and harm avoidance relative to mothers
in the other classes. Probands in this class reported
greater symptomatology than class 1 probands but
less than class 2 probands.
Comparisons between mothers and daughters
within latent classes indicated that mothers and
daughters in two of the classes (classes 1 and 2) dif-
fered significantly from each other within clusters
(p<0.001). More specifically, within classes 1 and 2,
mothers and daughters differed significantly from
each other on neuroticism, trait anxiety, and harm
avoidance, as well as drive for thinness, body dis-
satisfaction, and perfectionism. Within class 3, how-
ever, mothers and daughters differed significantly
from each other only on drive for thinness, body
Table 2. Descriptive information [mean (S.D.)] for study sample
EDI Drive for Thinness
EDI Body Dissatisfaction
MPS Perfectionism Total
STAI State Anxiety
STAI Trait Anxiety
TCI Harm Avoidance
TCI Reward Dependence
EDI, Eating Disorder Inventory-2; MPS, Multidimensional Perfectionism Scale;
STAI, Spielberger State-Trait Anxiety Inventory; NEO, Revised NEO Personality
Inventory; TCI, Temperament and Character Inventory; BIS, Barratt Impulsivity
Scale-11; YBC-EDS, Yale–Brown–Cornell Eating Disorder Scale; YBOCS, Yale–Brown
Obsessive Compulsive Scale; S.D., standard deviation; N.A., not assessed.
AN trios 455
dissatisfaction, and perfectionism (p<0.001). The class
3 mothers and daughters did not differ significantly
from each other on neuroticism, trait anxiety, or harm
Validation of classes
x2tests conducted to investigate whether AN subtype
or clinical status was related to family class member-
ship indicated that class membership was not signifi-
cantly related to probands’ illness subtype [x2(4)=
6.18, p=0.186, Cramer’s V=0.09] or clinical status
[x2(2)=2.75, p=0.253, Cramer’s V=0.09]. The moder-
ate symptomatology probands/healthy mothers class
(class 1) was composed of 55.8% RAN probands,
17.5% PAN and 26.7% BAN. The highest symptoma-
tology probands/moderate symptomatology mothers
class (class 2) was composed of 67.7% RAN probands,
14.6% PAN, and 17.7% BAN. The high symptoma-
tology probands/high symptomatology mothers class
(class 3) was composed of 58.6% RAN probands,
21.8% PAN and 19.6% BAN.
In the external validation, one-way ANOVAS with
post-hoc comparisons were conducted. There were no
significant differences between groups at the a=0.001
level (see Table 5). The proband current YBC-EDS
total score indicated a trend toward significance
[F(2,362)=4.55, p=0.011, g2=0.03], with class 3 pro-
bands reporting the highest scores on this variable
This study of temperament and personality charac-
teristics of AN probands and their parents identified
distinct patterns of traits within AN families. The three
distinct classes of trios were distinguished by levels of
symptoms on selected variables rather than qualitative
Table 3. Trio latent classes
Class 1 mean (S.D.)
Class 2 mean (S.D.)
Class 3 mean (S.D.)
24% (n=104)F (2,362)p value
EDI Drive for Thinness
EDI Body Dissatisfaction
STAI Trait Anxiety
TCI Harm Avoidance
EDI, Eating Disorder Inventory-2; MPS, Multidimensional Perfectionism Scale; NEO, Revised NEO Personality Inventory;
STAI, Spielberger State-Trait Anxiety Inventory; TCI, Temperament and Character Inventory; S.D., standard deviation.
456 M. J. Jacobs et al.
The first class of trios contained probands and
mothers with the least symptomatology. The patterns
of scores within the other two classes of trios were
characterized by counterbalancing scores for mothers
and probands. In the second class of trios (highest
symptomatology probands/moderate symptomatol-
ogy mothers), mothers with mid-range scores had
daughters with the highest proband scores. The
mothers in this class reported lower levels of perfec-
tionism and drive for thinness than AN mothers in the
other trio classes, although elevated compared to the
healthy comparison women (Woodside et al. 2002).
Significant differences between mothers and daugh-
ters on all variables within this class confirm the more
severe symptomatology of the probands.
Mothers with the highest scores on the trio
LPA variables had daughters with mid-range scores
relative to other probands. It should be noted that the
probands’ raw scores on a majority of variables were
higher than their mothers’ scores. Probands in this
class demonstrated higher levels of symptomatology
than the least symptomatic probands (moderate
symptomatology probands/healthy mothers, class 1)
and their own mothers. Unlike the other trio classes,
however, mothers and daughters in the high symp-
tomatology probands/high symptomatology mothers
class did not significantly differ on all variables in the
LPA. More specifically, they did not differ signifi-
cantly with respect to neuroticism, harm avoidance,
and trait anxiety. Thus, these mothers demonstrated
levels of personality, temperamental, and affective
disturbance in the same range as their daughters. The
significantly higher perfectionism of the probands
compared to their mothers provides support for
the notion that perfectionism may moderate the
relationship between personality,
and affective disturbances and the development and
maintenance of AN.
Table 4. Effect sizes and post-hoc tests for AN trio latent classes
Class 1 v.
Class 2 v.
Class 1 v.
EDI Drive for Thinness
EDI Body Dissatisfaction
STAI Trait Anxiety
TCI Harm Avoidance
AN, Anorexia nervosa; EDI, Eating Disorder Inventory-2; MPS, Multidimensional
Perfectionism Scale; NEO, Revised NEO Personality Inventory; STAI, Spielberger
State-Trait Anxiety Inventory; TCI, Temperament and Character Inventory;
N.A., not assessed.
AN trios 457
Taken together, the results of the trios LPA indicate
differences in severity in both probands and mothers
across the classes, rather than qualitative pattern dif-
ferences. The more severe symptomatology of two of
the classes [the highest symptomatology probands/
moderate symptomatology mothers (class 2) and the
high symptomatology probands/high symptoma-
tology mothers (class 3)] is consistent with the per-
vasive temperamental and behavioral disturbances
that have been identified previously in AN (Agras
et al. 2004). Consistent with our findings, a small study
examining temperament and character in AN daugh-
ters and parents found selected positive correlations
between daughters and mothers, but not between
daughters and fathers (Fassino et al. 2002). No larger,
more comparable studies could be identified. The
finding that more temperamentally healthy mothers
tended to have daughters with less severe tempera-
mental symptomatology relative to other probands
suggests that these daughters may benefit from a dif-
ferent genetic loading for these characteristics than
more highly symptomatic probands. When reflecting
on the mechanism whereby genetics might influence
risk for a complex trait such as AN, we envision the
action of many genes across risk domains including
appetite, weight regulation, and temperament. These
results indicate that ‘healthier’ mothers were not
associated with offspring with high severity of ED
symptomatology. It is conceivable that more extreme
temperamental traits (in both probands and their
mothers) may influence severity of symptoms ex-
pressed. We hypothesize that the transmission of
milder temperamental profiles may protect offspring
from developing more severe AN symptomatology.
This could reflect the direct genetic transmission of
milder temperamental traits, or could index the family
environment influenced by mothers with milder
temperaments, environments that may serve to con-
tain the expression of AN symptoms rather than
The risk factors for the development of EDs are
poorly understood. Findings in this study using LPA
to identify temperamental, personality, and affective
disturbances among family members are consistent
with previous reports from other Price Foundation
studies (Lilenfeld et al. 1998; Woodside et al. 2002; Keel
et al. 2004) as well as other studies (Fairburn et al. 1999;
Espina, 2003) noting familial personality profiles
in AN. In this study, class membership was more
strongly influenced by maternal and proband charac-
teristics. It is possible that other factors not captured in
this study, such as inflexibility and rigidity, may be
related to fathers (Lilenfeld et al. 1998). Perhaps the
assessment battery (which did not assess OC symp-
toms in parents) failed to capture dimensions that are
characteristic of fathers of individuals with AN.
Although neuroticism, trait anxiety, and harm
avoidance contributed the most to the determination
of class groups, mothers and daughters within classes
1 and 2 differed significantly on these variables. Given
the considerable genetic contribution thought to be
associated with these traits (Cloninger et al. 1993;
Jang et al. 1996; Price Foundation Collaborative
Group, 2001; Fassino et al. 2002), it may initially seem
Table 5. External validation ANOVA results for AN trio latent
Proband YBOCS total
2, 330 0.90.4 0.0
BIS Cognitive Impulsivity
STAI State Anxiety
AN, Anorexia nervosa; YBC-EDS, Yale–Brown–Cornell
Eating Disorder Scale; YBOCS, Yale–Brown Obsessive
Compulsive Scale; BIS, Barratt Impulsivity Scale-11; STAI,
Spielberger State-Trait Anxiety Inventory; TCI,
Temperament and Character Inventory; df degrees of
458 M. J. Jacobs et al.
counterintuitive that mothers and daughters within
two classes differed significantly on these traits. It may
be that the higher levels of severity among daughters
(relative to mothers) reflects the impact of lifetime
eating disordered behavior or may have driven that
behavior initially. In addition, there may be traits that
were not assessed that help to explain the mismatch.
We are just starting to understand the biology of AN
and it is not possible to understand or include all
potentially relevant factors.
Contrary to the initial hypotheses, the differences in
personality and temperament patterns among the trio
classes were not related to subtype or clinical status.
Potential implications are that differences in subtype
may not be related to family temperament and per-
sonality profiles and that profiles are stable to clinical
status. It is possible, however, that subtype results
were influenced by an under-representation of AN
probands with binge eating. The resulting latent
classes, distinguished by symptom levels rather than
by qualitatively distinct patterns, could reflect the
relative diagnostic homogeneity of the probands. We
would like to emphasize, however, that if a subtype
were truly homogeneous, this would be reflected in
the LPA results. Under-representation would only
seriously threaten the validity of the LPA at about 5%
representation. The selection of indicator variables
could also have influenced the resultant latent classes.
For example, including the EDI-2 bulimia subscale as
an indicator variable in the LPA (instead of in the
external validation) could have potentially produced
different class groupings. Nevertheless, it is not likely
that this would threaten the null finding with respect
to subtype, given that there were no significant dif-
ferences between classes on the bulimia subscale in the
Although no significant differences in trio class
membership were identified based on OC symptoms
of the probands, it should be noted that all three
classes of trios reported elevated OC symptoms rela-
tive to controls (Kaye et al. 1992; Rosenfeld et al. 1992;
Sunday & Halmi, 2000). This may indicate a ceiling
effect and is consistent with literature highlighting the
important role of OC symptoms in the etiology
(Lilenfeld et al. 1998) and course of AN (Keel et al.
The strengths of the present study include the large
sample size, comprehensive assessment protocol, di-
agnostic homogeneity of the probands, and inclusion
of both biological parents of individuals with AN.
Nevertheless, families included may differ systemati-
cally from families in which both parents were not
available and/or willing to participate. Other potential
sources of variance, particularly related to the in-
clusion of relatives who may have had other Axis I
psychiatric diagnoses (Kaye et al. 2004b) or the poss-
ible presence of parents with a lifetime ED diagnosis,
must be acknowledged. History of an ED may help to
explain the role of mothers compared to fathers in
determining class profiles. Risk factors for EDs are not
well understood and variables not captured by the
assessment battery in this study, including past par-
ental ED, may contribute to an enhanced understand-
ing of its findings (Jacobi et al. 2004). Finally, this study
does not contain an unaffected comparison group of
trios. Similar profiles of trios may exist within the
unaffected population. Nevertheless, exploring differ-
ences within the affected sample may help us to better
understand diversity within the ED population and to
explore genetic variants and commonalities.
A key finding of this study is the importance of
mothers’ and daughters’ traits relative to fathers’ in
the identification of temperament and personality
patterns in families affected by AN. The high symp-
tomatology probands/high symptomatology mothers
class (class 3) may represent a more homogeneous
and familial variant of AN and index an underlying
anxiety/harm avoidant dimension and/or propensity
to extreme fear conditioning hypothesized to be
related to AN (Strober, 2004). Identification of pheno-
types that evidence strong familiality can assist with
choosing optimal quantitative traits for inclusion in
linkage and association studies.
We thank the Price Foundation for support in the
clinical collection of participants and in data analysis.
Wethankthe staff of
Collaborative Group for their efforts in participant
screening and clinical assessments. We are indebted to
the participating families for their contribution of time
and effort in support of this study.
Declaration of Interest
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