European Eating Disorders Review
Eur. Eat. Disorders Rev. 10, 255–270 (2002)
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/erv.476
Paper
Pre-morbid Psychiatric Morbidity, Comorbidity
and Personality in Patients with Anorexia
Nervosa Compared to their Healthy Sisters
Andreas Karwautz1,4*, Sophia Rabe-Hesketh2, David A. Collier3
and Janet L. Treasure1
1
Eating Disorders Unit, Institute of Psychiatry, London, UK
Department of Biostatistics and Computing, Institute of Psychiatry,
London, UK
3
Department of Psychological Medicine, Institute of Psychiatry, London,
UK
4
University Clinic of Neuropsychiatry of Childhood and Adolescence,
University of Vienna, Austria
2
Anorexia nervosa (AN) has been linked with pre-morbid disorders, comorbidity,
and specific personality traits in between-family case–control studies. However,
these findings have not been replicated in within-family studies, and it is not
known whether these factors are linked specifically with AN or are shared
familial factors. We aimed to compare pre-morbid disorders, comorbidity, and
specific personality traits between sister-pairs discordant for AN. Forty-five
families with two sisters discordant for AN were retrospectively assessed by
interview and questionnaires. The proband with AN had mood disorders and
personality disorders (PDs) more frequently than their sister and had lower
scores of novelty seeking, self-directedness and cooperativeness, and higher
scores of harm avoidance, persistence, self-transcendence and of all EDI-2 scales.
In conclusion, major depression, cluster C PDs, persistence, harm avoidance,
and self-transcendence appear to be specifically linked to AN and to be
*Correspondence to: Dr A. Karwautz, Consultant Psychiatrist, Eating Disorders Unit, University
Clinic of Neuropsychiatry of Childhood and Adolescence, University of Vienna Medical School,
Waehringer Guertel 18–20, A-1090 Vienna, Austria. Tel: 0043-1-40400-3057. Fax: 0043-1-9147317.
E-mail: Andreas.Karwautz@univie.ac.at
Contract/grant sponsor: Austrian Science Foundation, Vienna.
Contract/grant number: J-1608-MED, 1998.
Contract/grant sponsor: University of Vienna, Austria.
Contract/grant sponsor: Austrian Ministry of Science.
Contract/grant sponsor: Action Research.
Contract/grant sponsor: European Community Framework V.
Contract/grant number: QLK1-1999-916.
Copyright # 2002 John Wiley & Sons, Ltd and Eating Disorders Association.
European Eating Disorders Review
10(4), 255–270 (2002)
A. Karwautz et al.
Eur. Eat. Disorders Rev. 10, 255–270 (2002)
individual-specific in nature. Major depression seems to be a risk factor for AN.
Copyright # 2002 John Wiley & Sons, Ltd and Eating Disorders Association.
Keywords: anorexia nervosa; sister-pairs; personality; comorbidity
INTRODUCTION
Between family case–control studies with unrelated subjects are an
important tool for the identification of risk factors and related traits
important in psychological disorders. However, associations might be
confounded by between-family differences such as socioeconomic status,
family structure, and cultural values which are often unmeasured and
ignored (Dick, Johnson, Viken, & Rose, 2000). The use of discordant
siblings (as close as possible in age) is a powerful tool to replicate and
clarify associations in disorders such as anorexia nervosa (AN). AN is
strongly associated with pre-morbid psychiatric disorders (e.g. Fairburn,
Cooper, Doll, & Welch, 1999; Gillberg, Rastam, & Gillberg, 1995;
Karwautz et al., 2001a), comorbidity with mood disorders (e.g. Halmi
et al., 1991; Herzog, Keller, Sacks, Yeh, & Lavori, 1992), anxiety disorders
(Braun, Sunday, & Halmi, 1994; Bulik, Sullivan, Fear, & Joyce, 1997),
substance use disorders (Herzog et al., 1992), and personality disorders
(e.g. Rosenvinge, Martinussen, & Ostensen, 2000; Wonderlich, Swift,
Slotnick, & Goodman, 1990). Patients with AN score at the extremes of
some temperament and personality dimensions (Klump et al., 2000;
Vitousek & Manke, 1994). In the present study we used a within-family
design of discordant sister-pairs for anorexia nervosa, to (1) control for
unmeasured potentially confounding factors and (2) to examine whether
these risk factors (premorbid axis-I disorders, PDs, personality traits) are
linked specifically to the sibling with AN.
SUBJECTS AND METHODS
Design
A case–control design was used to compare 45 sister pairs discordant for
AN. The part of the study relating to specific genetic and environmental
risk factors has been previously described elsewhere (Karwautz et al.,
2001a).
Recruitment
We approached women with AN who had volunteered to participate in
research and current patients with AN at the South London and
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Comorbidity in Anorexia Nervosa
Maudsley NHS Trust. To be included in the study the probands had to
have AN and have a sister who did not have any form of an eating
disorder (either AN, BN nor EDNOS). The sisters had to be less than 10
years apart in age and to have lived in the same family for a minimum of
8 years. If the patient had more than one sister, the sister closest in age
was approached.
Of 50 subjects with sisters that we approached, two declined to ask
their sister to participate. Of those who were interviewed two pairs were
excluded because the ‘unaffected’ sister had a covert eating disorder.
One pair was excluded because it became apparent during the interview
that they were not full biological siblings. Due to incomplete interview
schedules or insufficiently scored questionnaire measures, data on PDs,
temperament and character are available only for 43 and 40 pairs,
respectively. Of the 45 patients recruited 28 were research volunteers
and 17 were current in- and outpatients at the hospital. The protocol for
the study was reviewed by the Research Ethics Committee of the
Bethlem and Maudsley Trust. Patients and their sisters gave written
informed consent before inclusion in the study.
Assessment measures
A lifetime eating disorder history was assessed using a European
adaptation of the Longitudinal Interval Follow-up Evaluation (LIFE—
Keller et al., 1987). AN (restricting versus binge/purging subtype), and
lifetime status for major axis I disorders were diagnosed using the
Structured Clinical Interview for Mental Disorders, research version 2.0
(SCID-I). The reliability and validity of the SCID-I has been documented
with inter-rater agreement ranging from a kappa of 0.7 to 1.0. In order
to document a premorbid occurrence of psychiatric disorders we used
the method developed by Fairburn et al. (1999) to define onset of
the eating disorder as the age of the first persistent symptoms of the
disorder (called index age) and we asked the patients about the time
before the eating disorder started in order to get a measure of risk. We
used the criterion of 3 years without any episodes of binge eating to
define the restricting subtype of AN (as set by The Price Foundation
Collaborative Group, 2001). In order to assess axis II diagnoses we used
the International Personality Disorder Examination–ICD-10 module
(Loranger, Janca, & Sartorius, 1997), which is a structured interview
with an inter-rater reliability between 0.65 and 0.72 and a temporal
stability between 0.53 and 0.54 (Lenzenweger, 1999; Loranger et al.,
1994, 1997).
The following self-report measures were used.
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Eur. Eat. Disorders Rev. 10, 255–270 (2002)
Eating Disorders Inventory
The Eating Disorders Inventory-2 (EDI-2; Garner, 1991) is a widely used
self-report measure of eating disorder symptoms and putative vulnerability factors with excellent internal consistency, content validity,
criterion based validity, and construct validity and good test–retest
reliability in eating disordered and healthy control subjects (Garner,
1991). Five of the dimensions in this instrument were designed to
measure the underlying personality traits.
Temperament and Character Inventory
The Temperament and Character Inventory (TCI) (Cloninger, Przybeck,
Svrakic, & Wetzel, 1994) is a self-report instrument with 225 items which
measures dimension of temperament (novelty seeking, harm avoidance,
reward dependence, and persistence) and character (self-directedness,
cooperativeness, and self-transcendence). The internal consistency of
the composite scales is high (ranging from 0.76 to 0.87 for the
temperament scales and 0.84 to 0.89 for the character scales) (Cloninger
et al., 1994).
Procedure
Eighty-six per cent of the subjects were interviewed in person and the
remainder over the telephone. Each sister was interviewed independently. The senior author re-rated the taped interviews blind to case
status. The questionnaires were filled in after having the interviews
keeping the interviewer blind to the TCI and EDI-2 scores.
Data analysis
The clinical and demographic data from the two phenotypic extremes
(þ/ anorexia) was compared using paired t-tests. The sisters were
compared regarding the occurrence of the axis-I and axis-II disorders
using McNemar’s tests and regarding personality dimensions and
eating disorder-related psychopathology using paired t-tests. The
comorbidity and personality traits were compared by chi-squared or
t-tests between the AN subtypes. All main test results (e.g. the variable
‘any mood disorder’, ‘any PD’) were considered as statistically
significant at the 1 per cent level (p < 0.01). Because a difference in
comorbidity and PDs was found within the literature consistently in one
direction when comparing AN patients with unrelated controls, we
used tests with one-tailed p-values for these items when comparing AN
patients with related controls. Because the reports on the TCI scales in
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Eur. Eat. Disorders Rev. 10, 255–270 (2002)
Comorbidity in Anorexia Nervosa
AN were not of such a consistent pattern (in particular for the character
scales which have been reported in few studies only) we used tests with
two-tailed p-values for those.
If there were significant differences between the groups on a domain
level, a level of significance of p < 0.05 was accepted for additional
analyses on an item level. All analysis was carried out using SPSS-PC.
RESULTS
Clinical and demographic characteristics of the sister-pairs
The sisters were similar in age with a mean age gap of 3.2 þ/ 1.9 years.
The affected subjects had a mean age of 27.7 þ/ 8.5 years, the
unaffected sisters 27.4 þ/ 9.7 years. The mean age of first established
symptoms of an eating disorder (index age) was 15.3 þ/ 3.2 years. The
affected subject was the youngest of the pair in 49 per cent of the cases.
At the time of the interview the affected subjects had a mean BMI of 17.7
þ/ 3.7 kg/m2, whereas the unaffected sisters had a mean BMI of 22.4
þ/ 3.8. The minimum BMI of the affected sister was 13.1 þ/ 2.2 and
the median duration of the illness was 3 years (interquartile range (IQR)
1.8–6.5). Fifty-seven per cent of the fathers had professional occupations.
Eighteen per cent of the affected sisters were not working because of
medical reasons in comparison to 2 per cent (n ¼ 1) of the unaffected
sisters. Overall the affected subjects had a poorer level of career
adjustment than their sisters.
Inter-rater reliability
The raters, both unblinded (primary investigator) and blinded (senior
investigator) to case status, agreed in their ratings with a mean kappa
(SD) of 0.85 (0.2).
Premorbid axis-I morbidity (Table 1)
Forty per cent (n ¼ 18) of the anorexic patients had a diagnosis of any
DSM-IV mood disorder (versus 7 per cent (n ¼ 3) of the sisters,
chi2 ¼ 12.2, p < 0.001) prior to the onset of their eating disorder. Major
depressive episodes were present in 29 per cent (n ¼ 13) of the group
with AN and in 7 per cent (n ¼ 7) of their sisters (p ¼ 0.02). Anxiety
disorders were present equally (7 per cent (n ¼ 3) in both groups).
Substance-related disorders were rare in both sister groups. Separation
anxiety disorder was present in 11 per cent (n ¼ 5) in AN versus 2
per cent (n ¼ 1) in their sisters (n.s.).
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A. Karwautz et al.
Eur. Eat. Disorders Rev. 10, 255–270 (2002)
Table 1. Distribution of premorbid and lifetime rates of axis-I psychiatric
disorders among subjects with anorexia nervosa and their sisters (n ¼ 45;
McNemar’s test, two-tailed p-values)
Diagnosis
Axis-I disorders (premorbid occurrence)
Mood disorders
Any mood disorder ð2 Þ
Any major depressive episode
Major depressive disorder, single episode
Major depressive disorder, recurrent episodes
Dysthymia
Depressive disorder NOS
Anxiety disorders
Any anxiety disorder ð2 Þ
Panic disorder without agoraphobia
Panic disorder with agoraphobia
Specific phobia
Social phobia
Obsessive compulsive disorder
Posttraumatic stress disorder
Generalized anxiety disorder
Substance-related disorders
Any substance-related disord. (Fisher’s exact)
Alcohol abuse
Alcohol dependence
Abuse of other substances
Dependence on other substances
Disorders of infancy, childhood and adolescence
Separation anxiety disorder
Axis-I disorders (lifetime occurrence)
Mood disorders
Any mood disorder ð2 Þ
Any major depressive episode
Major depressive disorder, single episode
Major depressive disorder, recurrent episodes
Dysthymia
Depressive disorder NOS
Anxiety disorders
Any anxiety disorder ð2 Þ
Panic disorder without agoraphobia
Panic disorder with agoraphobia
Specific phobia
Social phobia
Obsessive compulsive disorder
Posttraumatic stress disorder
Generalized anxiety disorder
Patient
Sister
Test statistics
n ¼ 45 (%) n ¼ 45 (%) p (one-tailed)
18
13
10
3
4
0
(40)
(29)
(8)
(7)
(8)
(0)
3
3
3
0
0
0
(7)
(7)
(7)
(0)
(0)
(0)
< 0.001 (12.2)
0.01
n.s.
n.s.
n.s.
—
3
0
0
1
0
2
1
0
(7)
(0)
(0)
(2)
(0)
(4)
(2)
(0)
3
0
0
0
0
2
0
1
(7)
(0)
(0)
(0)
(0)
(4)
(0)
(2)
n.s.
—
—
n.s.
—
n.s.
n.s.
n.s.
0
0
0
0
0
(0)
(0)
(0)
(0)
(0)
0
0
0
0
0
(0)
(0)
(0)
(0)
(0)
—
—
—
—
—
5 (11)
1 (2)
n.s.
34
26
14
12
14
9
(76)
(58)
(31)
(27)
(31)
(20)
11
9
6
3
1
1
(24)
(20)
(13)
(7)
(2)
(2)
< 0.001 (21.5)
< 0.001
0.03
0.01
< 0.001
0.01
22
6
8
3
3
5
2
2
(49)
(13)
(18)
(7)
(7)
(11)
(4)
(4)
11
2
5
1
1
2
0
1
(24)
(4)
(11)
(2)
(2)
(4)
(0)
(2)
0.02 (4.79)
0.15
0.28
0.32
0.25
0.23
0.25
0.5
Continues
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Comorbidity in Anorexia Nervosa
Table 1. Continued
Diagnosis
Patient
Sister
Test statistics
n ¼ 45 (%) n ¼ 45 (%) p (one-tailed)
Separation anxiety disorder
Substance-related disorders
Any substance-related disord. (Fisher’s exact)
Alcohol abuse
Alcohol dependence
Abuse of other substances
Dependence on other substances
5 (11)
1 (2)
0.11
8
6
3
2
0
1
1
0
0
0
0.02
0.03
0.13
0.25
—
(18)
(13)
(7)
(4)
(2)
(2)
(0)
(0)
(0)
Lifetime axis-I psychopathology (Table 1)
Seventy-six per cent (n ¼ 34) of the anorexic patients had a lifetime
diagnosis of any DSM-IV mood disorder (versus 24.4 per cent (n ¼ 11) of
the sisters, p < 0.001). Forty-nine per cent (n ¼ 22) of the anorexic subjects
had any form of anxiety disorder (versus 24 per cent (n ¼ 11) of the
sisters n.s.), and 18 per cent (n ¼ 8) had any substance-related disorder
(versus 2 per cent (n ¼ 1) of the sisters; n.s.).
Comorbid axis-II psychopathology (Table 2)
Fifty-four per cent (n ¼ 23) of the women with AN had at least one PD
diagnosis, compared to 7 per cent (n ¼ 3) of the sisters, p < 0.0001).
Thirty-four per cent (n ¼ 15) fulfilled criteria of one PD, 7 per cent (n ¼ 3)
had two, and 12 per cent (n ¼ 5) had three PD diagnoses. The sister-pairs
Table 2. Distribution of personality disorder diagnoses among subjects with
anorexia nervosa and their sisters (McNemar’s test with n ¼ 43 for Axis II
disorders; two-tailed p-values)
Personality disorder
(IPDE—definite diagnoses)
Any personality disorder (Fisher’s exact test)
Schizoid
Paranoid
Emotional unstable, impulsive type
Emotional unstable, borderline type
Dissocial
Histrionic
Dependent
Anankastic
Anxious
Unspecific
Patients
Sisters
n ¼ 43 (%) n ¼ 43 (%)
23
4
1
3
2
0
0
6
10
9
1
(54)
(9.1)
(2.3)
(6.8)
(4.5)
(0)
(0)
(13.6)
(22.7)
(20.5)
(2.3)
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3
1
0
0
0
0
0
0
2
1
0
(7)
(2.3)
(0)
(0)
(0)
(0)
(0)
(0)
(4.7)
(2.3)
(0)
Test statistics
p (one-tailed)
< 0.001
0.13
0.5
0.13
0.25
—
—
0.02
0.01
0.02
0.5
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A. Karwautz et al.
Eur. Eat. Disorders Rev. 10, 255–270 (2002)
differed significantly in particular in the frequency of anankastic PD
(n ¼ 10 versus n ¼ 2), anxious PD (n ¼ 9 versus n ¼ 1) and dependent PD
(n ¼ 6 versus n ¼ 0) (Cluster C diagnoses). All other PD diagnoses were
very rare in the patient group and nearly absent in the controls.
Temperament and character dimensions, and personality traits:
comparing the sister-pairs
The sisters differed in their temperament and character pattern (TCI)
apart from the reward dependence dimension. The subjects with AN
were lower in novelty seeking (t ¼ 4.36, df ¼ 39, p < 0.0001), selfdirectedness (t ¼ 9.38, df ¼ 39, p < 0.0001), and cooperativeness
(t ¼ 2.61, df ¼ 39, p ¼ 0.013), and higher in harm avoidance (t ¼ 7.88,
df ¼ 39, p < 0.0001), persistence (t ¼ 3.82, df ¼ 39, p < 0.0001), and selftranscendence (t ¼ 2.64, df ¼ 39, p ¼ 0.012) than their non-eating disordered sisters. The women with eating disorders had higher scores on
all of the personality subscales of the EDI-2 (all paired samples t-tests,
df ¼ 39, p < 0.001).
Defining the subgroups
Sixty-four per cent (n ¼ 29) of the probands fulfilled the criterion for
restricting AN i.e. 3 years without any episodes of binge eating. The
restricting and the bingeing subgroup were similar in age, age at first
symptoms, birth weight, age at lowest maintained weight, and BMI at
the time of the interview. However, the restricting subgroup reached
significantly lower BMI scores during the course of their disorder (AN/
RES–AN/BP: mean BMI (SD); 12.4 (2.1)–14.4; t ¼ 3.22, p ¼ 0.002) and
reported lower scores in the bulimia subscale of the EDI-2 (mean 2.0 þ/
2.9 versus 8.1 þ/ 6.6; t ¼ 4.21; df ¼ 40; p < 0.001).
There were no significant differences either for premorbid or lifetime
diagnoses within the domains of any mood, anxiety, substance-related
disorder, and PD. The subgroups did not significantly differ in the
scores on the TCI or the personality dimensions of the EDI-2.
DISCUSSION
All human psychological traits and psychiatric disorders are composed
of both genetic and environmental risk factors in varying proportions.
Environmental factors can be shared (such as parental divorce) on nonshared (such as individual experience of abuse). Except for general
cognitive ability, there is good evidence from twin studies that
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Comorbidity in Anorexia Nervosa
psychopathology and personality are composed almost entirely of nonshared environment and genetic factors (Plomin, deFries, McClearn, &
McGuffin, 2000), with shared environment playing a minor role. It is
thus important to focus on individual-specific environments in
determining the risk factors which lead to psychiatric morbidity, and
twins or siblings discordant for a disease or trait are a powerful
approach to measuring this. Case–control studies with unrelated
controls cannot determine whether risk factors and behavioural
associations are a result of shared environment, non-shared environment and/or genetic factors. Twin studies and model fitting have
demonstrated that overall, shared family environment is not of major
importance to the aetiology of eating disorders (Bulik, Sullivan, Wade, &
Kendler, 2000b; Pike & Plomin, 1996; Plomin, Asbury, & Dunn, 2001),
but are weak for AN because of lack of statistical power. Most recently, a
twin-study in anorexic syndromes reported that additive genetic and
non-shared environmental factors in the best-fitting model accounted
for 74 and 26 per cent, respectively of the variance of broadly defined
AN-syndromes (Klump, Miller, Keel, McGue, & Iacono, 2001). Twin
studies also do not address whether risk factors such as pre-morbid
depression and PDs, which are not unique to eating disorders, are
shared or non-shared risk factors. Even obviously shared factors such as
parental divorce affect children differently, and it is important to assess
differences between siblings in this context.
Strength of the study design
It was Strober (1991) who recognized the value of a behavioural–genetic
approach for an aetiological model of AN integrating genetics, biology,
and psychology and focusing on individual differences. The present
study was designed to find individual-specific differences between
sisters discordant for AN both before the onset and after the onset of the
eating disorder, since these factors will be important in triggering and
maintaining the state of disease. We specifically focused on individual
differences in psychiatric comorbidity and temperamental and character
traits between the two sisters discordant for AN. The use of agedisplaced sister-pairs discordant for the outcome of interest is seen as
powerful tool (Dick et al., 2000) (a) to replicate associations of AN and
behavioural risk factors seen in between-family studies in a withinfamily design, i.e. examining whether the risk factors and related traits
are individual-specific or partly shared familial factors present also in
sisters without an eating disorder; (b) to clarify associations for
uncommon disorders such as AN, where even large twin registries
cannot provide enough power for risk-factor analyses (Bulik et al.,
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Eur. Eat. Disorders Rev. 10, 255–270 (2002)
2000b); and (c) to control for unmeasured potentially confounding
variables like socioeconomic status, family structure, religious, and
cultural values.
Limitations of the study
The study has several limitations. The primary investigator was not
blind to the eating disorder diagnosis. However, there was good
reliability of the ratings made by the blind assessor. Furthermore, a
meta-analysis on assessment of PDs described only minor differences
between blinded and unblinded ratings in eating disordered samples
(Rosenvinge et al., 2000). A small proportion of subjects were
interviewed by telephone. Although this limits access to non-verbal
cues, studies have found that telephone interviews can be as reliable
as face-to-face interviews in making axis-I and axis-II diagnoses
(Colombotos, 1969; Rhode, Lewinsohn, & Seeley, 1997). The sample
size was too small to give definitive information about AN subtypes.
Another limitation is the retrospective account of pre-morbid psychiatric morbidity, thus causing possible recall bias. However, Brewin,
Andrews and Gotlib (1993) found retrospective data reliable when they
were assessed via personal interviews and the items were behaviourally
described. Furthermore, it remains unclear, whether personality traits
are completely stable over time (e.g. before illness, during illness).
However, there has been some evidence that IPDE ratings of personality
are relatively stable over a 4-year period of time (Lenzenweger, 1999).
The two sources of recruitment tapped into a broad spectrum of cases.
The hospital sample has cases at the severe end of the spectrum as the
South London and Maudsley NHS Trust is both a tertiary referral
service as well as providing local services for the 2 million community
in Southeast London. The volunteers were recruited from a variety of
sources and this group had a broad range of severity and utilization of
services.
Comparison with previous work on premorbid morbidity
and axis-I comorbidity
We found that the women with AN had higher rates of mood disorders,
in particular major depressive episodes before the age at which AN
developed. Also the lifetime occurrence of mood disorders (in particular
recurrent major depressive episodes, dysthymia, and DEPNOS) was
significantly higher in the AN group. The percentages found are in line
with the literature reporting approximately one-third of patients with
AN having a mood disorder prior to onset (Braun et al., 1994; Fairburn
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Comorbidity in Anorexia Nervosa
et al., 1999; Gillberg et al., 1995; Karwautz et al., 2001a). The lifetime
prevalence rate of mood disorders we found is within the range
reported in several other studies which report rates between 36 and 82
per cent (Braun et al., 1994; Halmi et al., 1991; Herzog et al., 1992).
Anxiety disorders tended to be more common in the patient group
and substance-related disorders were rarely found in the sister-pairs
studied. There is little information on the premorbid occurrence of
anxiety disorders although in those comorbid for social phobia, the
anxiety disorder preceded onset in 79 and 90 per cent of cases
respectively (Braun et al., 1994; Bulik et al., 1997). The lifetime
prevalence rate of anxiety disorders given in the literature lies between
20 and 60 per cent (Braun et al., 1994; Bulik et al., 1997; Herzog et al.,
1992), and that of substance use disorders between 0 and 36 per cent
(Braun et al., 1994; Herzog et al., 1992). Our data is in keeping with these
rates.
Comparison with previous work on axis-II comorbidity
Personality disorders (especially those in cluster C) were significantly
more prevalent in the patient group. The rates and the distribution
found in our sample is in keeping with the literature which reports that
between 22 and 80 per cent of patients with AN also fulfil the criteria for
a personality disorder (PD) (average proportion of any PD in AN: 0.50
according to Inceoglu, Franzen, Backmund, & Gerlinghoff, 2000;
Rosenvinge et al., 2000). The average proportion of cluster C PDs in
AN according to the meta-analysis is 0.45 (Rosenvinge et al., 2000), thus
dominating in AN. In particular, the frequency of anankastic PD, which
we found to be the most common of the PDs in our sample, lies within
the range of 10 and 60 per cent for restricting AN patients (Rastam &
Gillberg, 1992; Wonderlich et al., 1990). These PDs (and/or the traits that
underpin them) may precede onset (Gillberg et al., 1995) and persist
after recovery (Gillberg et al., 1995; Halmi et al., 1991; Srinivasagam et al.,
1995; Wentz-Nilsson, Gillberg, Gillberg, & Rastam, 1999). Indeed it has
been suggested that anankastic PD may be the broader phenotype that is
present in the families of people with an eating disorder (Lilenfeld et al.,
1998).
Comparison with previous work on temperament, character,
and personality traits
It was Strober (1991) who first integrated the organismic approach to
temperament by Cloninger into a model of aetiology for AN focusing on
self-development (Karwautz et al., 2001b). In terms of these dimensions
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Eur. Eat. Disorders Rev. 10, 255–270 (2002)
of personality (temperament and character) the women with AN
differed markedly from their sisters, scoring lower in novelty seeking,
self-directedness, and cooperativeness, and higher in harm avoidance,
persistence, and self-transcendence and higher in all the dimensions of
the EDI-2.
The data on temperamental traits are fairly consistent over the
existing studies and our data (most recently: Diaz-Marsa, Carrasco, &
Saiz, 2000; Klump et al., 2000; The Price Foundation Collaborative
Group, 2001). Women with AN consistently have high scores for harm
avoidance and persistence. After recovery, harm avoidance remains
high (Casper, 1990; Kleifield, Sunday, Hurt, & Halmi, 1994) and novelty
seeking remains low (Casper, 1990). To our knowledge, data on the
character dimensions of personality (measured by TCI ratings) has
been reported in AN in detail in only two studies, showing high
harm avoidance and low self-directedness being associated with
chronicity, and high self-directedness and high cooperativeness scores
with full recovery (Bulik, Sullivan, Fear, & Pickering, 2000a; Klump et al.,
2000).
Overall the differences we found between AN patients and their noneating disordered sisters are similar to those of other published samples
comparing AN patients and unrelated controls in terms of clinical and
demographic features, axis-I, axis-II comorbidity, temperamental, and
character traits, thus replicating by and large the findings of studies
using between-family designs.
What has this study comparing patients and their sisters added
to the knowledge derived from case–control studies assessing
differences between patients and unrelated controls?
(1) Our study suggests that the differences found in morbidity prior to
onset are non-shared rather than shared risk factors. The premorbid and
comorbid disorders we found would be encompased in Fairburns
domain of ‘personal vulnerability’ (Fairburn et al., 1999). (2) Our study
suggests further, that the lifetime occurrence of comorbid psychiatric
disorders are non-shared markers of disease, which may contribute to
the maintenance of AN. (3) Concerning PDs and personality traits, and
given their relative stability (Lenzenweger, 1999), our study suggests the
non-shared nature of those disorders and traits as factors of ‘personal
vulnerability’. (4) The use of healthy sisters as controls meant that many
cultural and family factors were accurately matched as studies using
unrelated case–control samples are by definition not able to distinguish
whether the vulnerability factors are shared or individual-specific
factors (Dick et al., 2000).
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Comorbidity in Anorexia Nervosa
Further research
One major implication of this study is that mood disorders and
temperament and character traits are linked to the development of AN
and are not-shared factors. From the present data it is uncertain to what
extent these risk factors arise both from a general genetic predisposition
to psychopathology and from non-shared events. In support of a
pleiotropic genetic factor (i.e. one which increases general risk of
psychiatric illness) is the finding that there is an overlap of the
heritability between AN and depression (Wade, Bulik, Neale, &
Kendler, 2000).
ACKNOWLEDGEMENTS
We are grateful to all sufferers and their sisters for volunteering for this
study and to Ms Joyce Ballantyne for giving financial support. This
study was supported in part by an Erwin Schrödinger Fellowship
(J-1608-MED, 1998) from the Austrian Science Foundation, Vienna,
Austria, a grant from the University of Vienna, Austria, a grant from the
Austrian Ministry of Science to AK, a grant from Action Research and a
grant from European Community Framework V (QLK1-1999-916) to
AK, DAC, and JLT.
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