REGULAR ARTICLE
Influence of Overanxious Disorder of Childhood on the
Expression of Anorexia Nervosa
T.J. Raney, PhD1
Laura M. Thornton, PhD2
Wade Berrettini, MD3
Harry Brandt, MD4
Steven Crawford, MD4
Manfred M. Fichter, MD5,6
Katherine A. Halmi, MD7
Craig Johnson, PhD8
Allan S. Kaplan, MD9
Maria LaVia, MD1
James Mitchell, MD10
Alessandro Rotondo, MD11
Michael Strober, PhD12
D. Blake Woodside, MD8
Walter H. Kaye, MD2
Cynthia M. Bulik, PhD1*
ABSTRACT
Objective: Childhood anxiety often precedes the onset of anorexia nervosa (AN)
and may mark a liability to the emergence of an eating disorder for some
women. This study investigates the prevalence of overanxious disorder (OAD)
among women with AN and explores
how OAD impacts AN symptoms and personality traits.
Method: Participants were 637 women
with AN who completed an eating disorders history, the Structured Clinical Interview for DSM-IV Axis I Disorders, and
assessments for childhood anxiety, eating
disorder attitudes, and associated personality traits.
Results: Of 249 women (39.1%) reporting a history of OAD, 235 (94.4%) met cri-
Introduction
Clinical and epidemiological studies indicate that a
substantial portion of women with anorexia nervosa
Accepted 12 October 2007
Supported by Price Foundation.
*Correspondence to: Cynthia M. Bulik, Department of Psychiatry,
University of North Carolina at Chapel Hill, 101 Manning Drive, CB
#7160, Chapel Hill, NC 27599-7160. E-mail: cbulik@med.unc.edu
1
Department of Psychiatry, University of North Carolina at
Chapel Hill, Chapel Hill, North Carolina
2
Department of Psychiatry, University of Pittsburgh, Pittsburgh,
Pennsylvania
3
Center for Neurobiology and Behavior, University of
Pennsylvania School of Medicine, Philadelphia, Pennsylvania
4
Sheppard Pratt Hospital, Baltimore, Maryland
5
Department of Psychiatry, University of Munich (LMU), Munich,
Germany
6
Roseneck Hospital for Behavioral Medicine, Prien, Germany
7
New York Presbyterian Hospital, Weill Medical College of
Cornell University, White Plains, New York
8
Laureate Psychiatric Clinic and Hospital, Tulsa, Oklahoma
9
Program for Eating Disorders, Toronto General Hospital,
Toronto, Toronto, Ontario, Canada
10
Neuropsychiatric Research Institute, Fargo, North Dakota
11
Department of Psychiatry, University of Pisa, Pisa, Italy
12
Semel Institute for Neuroscience and Human Behavior,
Department of Psychiatry and Behavioral Science, University of
California at Los Angeles, Los Angeles, California
Published online 22 January 2008 in Wiley InterScience
(www.interscience.wiley.com). DOI: 10.1002/eat.20508
C 2008 Wiley Periodicals, Inc.
V
326
teria for OAD before meeting criteria for
AN. In comparison to those without OAD,
women with AN and OAD self-reported
more extreme personality traits and attitudes and they engaged in more compensatory behaviors.
Conclusion: Among individuals with
AN, those entering AN on a pathway via
OAD present with more severe eating disC 2008 by Wiley Periodorder pathology. V
icals, Inc.
Keywords: anorexia nervosa; overanxious disorder; genetic; childhood anxiety; social phobia; comorbid anxiety
disorders; panic disorder; anxiety disorder; twin studies; agoraphobia
(Int J Eat Disord 2008; 41:326–332)
(AN) report lifetime comorbid anxiety disorders.1–3
Across studies, the lifetime prevalence of at least one
anxiety disorder among patients with AN ranged
between 23 and 54%.1 Comorbid anxiety disorders
occur across AN subtypes with approximately equal
frequency.2–5 Generalized anxiety disorder, obsessive
compulsive disorder, and social phobia are the most
common comorbid anxiety disorders reported, and
they occur significantly more frequently in individuals with AN than in controls.1,2,5
Anxiety disorders commonly precede the onset
of the eating disorder1,2,6,7 and persist even after
long-term weight restoration8 suggesting a more
fundamental underlying anxious trait that is independent of nutritional state. Twin studies have
established a substantial contribution of genetic
factors to anxiety disorders with heritability estimates for both broadly defined generalized anxiety
disorder and panic disorder around 40%.9 Similarly,
twin studies examining the contribution of genetic
factors in the development of eating disorders
report moderate contributions of additive genetic
factors. The heritability of AN has been estimated
to be between 33 and 84%, and the heritability of
BN between 28 and 83%10–13 with the remaining
variance in liability to both disorders attributable
to individual specific environmental factors, and
with negligible impact of shared environmental
International Journal of Eating Disorders 41:4 326–332 2008
OAD OF CHILDHOOD AND AN
factors. In short, there is considerable evidence
that risk for eating disorders is influenced by
genetic factors.
Twin studies also suggest that eating disorders
and anxiety disorders may have shared genetic
transmission. Keel et al.14 examined the comorbidity of anxiety and eating disorders in monozygotic
twins who were discordant for eating disorder
symptoms. They found that twins with eating disorder symptoms were significantly more likely to
have an unaffected cotwin with an anxiety disorder,
suggesting a shared transmission for anxiety and
eating disorders. Silberg and Bulik15 examined longitudinally reported data in teenage twin girls to
identify common genetic liability among anxiety,
depression, and eating disorder symptoms in early
and late adolescence. Using multivariate genetic
modeling, they identified a common genetic factor
that influences the liability of childhood anxiety,
separation anxiety, depression, and eating problems which remains influential throughout development. They also identified a genetic factor associated with early onset eating problems, but not
associated with later eating problems or any mood
disturbance. These findings suggest that anxiety
and eating disturbances may share a common genetically influenced liability. However, that particular genetic liability may be only one of a variety of
pathways to developing an eating disorder.
Although shared liability between anxiety disorders and eating disorders has been suggested, and
the onset of anxiety disorders often predates the
onset of eating disorders, very little attention has
been directed to understanding the impact that
childhood anxiety disorders have on the subsequent
expression and development of AN. Therefore, in a
large phenotypically well-characterized sample of
individuals with AN we (1) report the prevalence of
overanxious disorder (OAD), (2) explore the impact
of OAD on the expression and severity of eating disorder symptoms and personality traits, and (3)
explore the relation between OAD and other anxiety
disorders in a sample of women with AN.
Method
Participants
Participants were recruited for a multisite international
Price Foundation Genetic Study of Eating Disorders
focusing on individuals with AN and their parents (‘‘AN
Trios’’). This study was designed to identify susceptibility
loci involved in the risk for eating disorders. Informed
consent was obtained from all study participants, and all
International Journal of Eating Disorders 41:4 326–332 2008
sites received approval from their local institutional
review board.
Male and female probands affected with AN were
recruited from nine sites in North America and Europe
including Pittsburgh (W.H.K), New York (K.A.H.), Los
Angeles (M.S.), Toronto (A.S.K., D.B.W.), Munich (M.M.F.),
Pisa (A.R.), Fargo (J.M.), Baltimore (H.B., S. C.), and Tulsa
(C.J.), between 2000 and 2003. Probands were required to
meet the following criteria: (a) modified DSM-IV (APA,
1994) lifetime diagnosis of AN, with or without amenorrhea; (b) low weight that is/was less than the fifth percentile of body mass index (BMI) for age and gender on the
chart of a National Health and Nutrition Examination Survey epidemiologic sample16; (c) onset before the age of 25
years; (d) weight that is/was controlled through restricting
and/or purging, which includes vomiting, use of laxatives,
diuretics, enemas, suppositories, or ipecac; (e) age between 13 years and 65 years; (f) Caucasian (one grandparent from another racial or ethnic group was acceptable);
and (g) study diagnostic criteria were met at least 3 years
before study entry. This last inclusion criterion ensured
that AN individuals who were unlikely to develop binge
eating were appropriately classified, as research has shown
that most binge eating develops within the first 3 years of
illness in AN.17–21 Potential participants were excluded if
they reported a maximum BMI since puberty, [27 kg/m2
for females and [27.8 kg/m2 for males. This exclusion of
individuals who were overweight or obese was designed to
increase sample homogeneity.
Measures and Interviews
Demographic and Clinical Variables. Data relative to
current age, age at onset, and current, minimum, and
maximum BMI were included in the analyses.
Eating Disorder Diagnoses and Associated Features. Along
the lines of Lilenfeld et al.,22 Kaye et al.,2 and Godart
et al.,4 this study used lifetime histories of eating disorder
behaviors in the categorization of eating disorder subtypes to capture subtype crossover for more accurate
classification. Lifetime histories of eating disorders and
the presence or absence of eating disorder behaviors
(e.g., dieting, binge eating, purging) in probands were
assessed with the Structured Inventory for Anorexia
Nervosa and Bulimic Disorders (SIAB)23 and with an
expanded version of Module H of the Structured Clinical
Interview for DSM-IV Axis I Disorders (SCID).24 The
training procedures for the SIAB and SCID have been
described in detail elsewhere.25 Interviewers were mental
health professionals with at least a master-level degree
(most current interviewers were Ph.D. psychologists)
who underwent centralized training and certification on
all study interviews.
On the basis of detailed clinical interview data, participants were subtyped as follows: AN, restricting subtype
327
RANEY ET AL.
(RAN, absence of lifetime purging or binging; n 5 228),
AN, purging subtype (PAN, purging in the absence of lifetime binging; n 5 172); AN, binging subtype (BAN, binging, with or without purging; n 5 108), or diagnoses of
both AN and BN during the course of illness (ANBN, n 5
108). The Eating Disorder Inventory22 (EDI-2)26 was
also used to assess disturbed eating attitudes and related
pathology.
Anxiety Disorder Diagnoses. The presence of OAD was
assessed using the Schedule for Affective Disorders and
Schizophrenia - Lifetime version (SADS-L, as modified by
Merikangas et al.27 for DSM-III-R diagnoses) in 90% of
the sample and by the K-SADS28 (modified for retrospective reporting) in 10% of the sample. Diagnostic algorithms were constructed to ensure compatibility across
instruments. Other anxiety disorders were assessed with
the Structured Clinical Interview for DSM-IV (SCID I).24
OAD was chosen as our target disorder for two reasons.
First, the SCID only assessed GAD in the past 6 months
and we were most interested in childhood onset anxiety.
Second, the prevalence of SAD was too low to yield
meaningful comparisons.
Personality and Character Traits. Temperament and
character dimensions were measured with the Temperament and Character Inventory (TCI).29 Perfectionism was
assessed with the Frost Multidimensional Perfectionism
Scale (MPS),30 and trait levels of anxiety were assessed
with the State-Trait Anxiety Inventory (STAI Form Y-1).31
Obsessive-compulsive symptoms were assessed with two
different measures: the Yale-Brown Obsessive Compulsive Scale (YBOCS)32 and the Yale-Brown-Cornell Eating
Disorder Scale (YBC-EDS).33 The Y-BOCS is a semistructured interview designed to assess presence and severity
of obsessive thoughts and compulsive behaviors typically
found among individuals with obsessive compulsive disorder. The YBC-EDS assesses obsessive-compulsive features specific to eating disorders (e.g., those related to
food, eating, weight, and exercise). The Revised NEO Personality Inventory (NEO PI-R)34 is an assessment of personality based on the five-factor model of personality,
and it measures the interpersonal, motivational, emotional, and attitudinal styles of adults and adolescents.
the various eating disorder related behaviors was
assessed using logistic regressions. Differences between
the groups in all continuous measures were determined
using analysis of variance with eating disorder subtype
entered as an additional covariate. All p-values were
corrected for multiple tests using the false discovery rate
(FDR).36
Results
A total of 744 participants met criteria for a lifetime
diagnosis of AN using the SCID and SIAB. Of those,
13 (1.7%) were males and were excluded from analyses due to small sample size. Seventy participants
who were not assessed for OAD or had missing anxiety disorders data were removed from the analysis.
An additional 24, who were determined to have a
lifetime diagnosis of separation anxiety disorder
(SAD), but not OAD were also not included. The
resulting sample size was 637.
Prevalence of Overanxious Disorder
Two hundred forty-nine women (39.1%) met criteria for OAD. Significant differences emerged in
the prevalence of OAD across AN subtypes (RAN 5
32.0%, PAN 5 43.8%, BAN 5 40.8%, ANBN 5
49.0%; v2 5 11.5, df 5 3, p 5 .009). Specifically, the
PAN and ANBN groups had significantly higher
prevalence of OAD than the RAN group. Of the
women with OAD, 235 (94.4%) met criteria for OAD
before they met criteria for AN. Six (2.4%) had AN
at least 1 year prior to the onset of OAD and eight
(3.2%) had onset of both AN and OAD in the same
year. There was no difference in the age of onset of
AN between those with OAD and those without
OAD. For those with OAD, there was no difference
in the age of onset of eating disorders between
those with other anxiety disorders and those without.
Eating Disorder Symptoms and Features
Statistical Analyses
All statistical analyses were conducted using SAS/
STAT1 9.1 software.35 To determine the prevalence of
OAD in individuals with eating disorders across subtypes,
chi-square tests were used to test between-group differences. v2 tests were also used to determine differences
between the OAD and no OAD group in prevalence of
anxiety disorders. In order to assess the effects of OAD independent of any other anxiety disorder, the presence or
absence of any other anxiety disorder was entered as a
covariate in all of the following analyses. Differences
between the OAD and no OAD groups in prevalence of
328
As shown in Table 1, women with a history of
OAD more often reported the use of appetite suppressants (v2 5 16.60, p \ .001), vomiting (v2 5
20.13, p \ .001), enemas (v2 5 8.55, p 5 .008), ipecac (v2 5 10.45, p 5 .004), diuretics (v2 5 8.30, p 5
.009), and laxatives (v2 5 9.97, p 5 .004) to control
weight. In addition, women with histories of OAD
reported longer total duration of eating disorder
symptoms than those without OAD (F 5 27.90,
p 5 .01). They also reported greater EDI body dissatisfaction (F 5 11.42, p 5 .003), drive for thinness (F 5 10.22, p 5 .004), bulimia (F 5 11.31,
International Journal of Eating Disorders 41:4 326–332 2008
OAD OF CHILDHOOD AND AN
TABLE 1. Frequency of various eating disorder behaviors by OAD: % (N) and logistic regression results comparing the
two groups, presence or absence of any other anxiety diagnoses was entered as a covariate in all models*
Binge eating
Fasting
Exercise
Appetite suppressants
Vomiting
Enemas
Ipecac
Diuretics
Laxatives
Any purging
Weight Phobia – SIAB
Self Esteem – SIAB
Body Image – SIAB
No OAD (N 5 388)
OAD (N 5 249)
v2 (p-Value)
OR (95% CI)
24.5 (95)
45.4 (176)
46.1 (179)
22.2 (86)
37.2 (144)
2.3 (9)
3.6 (14)
8.3 (32)
28.4 (110)
48.8 (188)
83.5 (324)
90.7 (351)
92.8 (360)
32.1 (80)
59.7 (148)
56.2 (140)
42.3 (105)
56.2 (12)
8.1 (20)
9.3 (23)
19.3 (48)
44.2 (110)
66.5 (165)
92.0 (229)
96.8 (241)
97.6 (243)
4.27 (.06)
2.10 (.18)
1.08 (.35)
16.60 (\.001)
20.13 (\.001)
8.55 (.008)
10.45 (.004)
8.30 (.009)
9.97 (.004)
16.35 (\.001)
3.37 (.10)
5.21 (.04)
2.12 (.18)
—
—
—
2.16 (1.49, 3.13)
2.22 (1.56, 3.15)
3.48 (1.43, 8.42)
3.43 (1.58, 7.42)
2.11 (1.26, 3.53)
1.78 (1.24, 2.55)
2.06 (1.45, 2.94)
—
2.48 (1.08, 5.66)
—
*All p-values have been adjusted using FDR.
p 5 .003), and YBC-EDS food preoccupations (F 5
5.65, p 5 .03) (see Table 2).
2.79, p 5 .01) and obsessive compulsive disorder (t
5 3.78, p \ .001), but not for the other anxiety disorders.
Personality and Temperament
In comparison to AN women without OAD,
women with OAD reported greater TCI harm avoidance (F 5 17.23, p \ .001) and persistence (F 5
9.36, p 5 .006), STAI trait anxiety (F 5 28.84, p \
.001), and lower TCI self-directedness (F 5 7.81,
p 5 .01) and novelty seeking, (F 5 5.68, p 5 .03)
(Table 2).
In comparison to AN women without OAD, those
with OAD also reported more perceived MPS parental criticism (F 5 36.24, p \ .001), higher parental expectations (F 5 11.61, p 5 .003), higher personal standards (F 5 11.93, p 5 .003), greater concern over mistakes (F 5 32.27, p \ .001), and
greater doubts about actions (F 5 25.56, p \ .001)
(Table 2). Also, women with AN and OAD reported
lower NEO-PI R extraversion (F 5 5.34, p 5 .04)
and higher neuroticism (F 5 10.13, p \ .001) than
those without a history of OAD.
OAD and Other Anxiety Disorders
Individuals with OAD were more likely than
those without OAD to develop additional anxiety
disorders (Table 3). More participants with OAD
were also diagnosed with generalized anxiety disorder, (v2 5 42.58, p \ .001), panic disorder (v2 5
9.33, p 5 .002), obsessive compulsive disorder (v2 5
40.74, p \ .001), social phobia (v2 5 37.11, p \
.001), or specific phobia (v2 5 17.84, p \ .001). The
prevalence of agoraphobia was not related to OAD
history; however, agoraphobia was relatively
uncommon in this sample. For the participants
who developed another anxiety disorder, the
presence of OAD was also associated with earlier
age of onset for generalized anxiety disorder (t 5
International Journal of Eating Disorders 41:4 326–332 2008
Conclusion
To our knowledge, this is the first study to report
estimates of the prevalence of overanxious disorder
of childhood among women with AN. Although
OAD no longer exists in the DSM-IV, we have benefited from the inclusion of that diagnosis in our
assessment in order to explore more carefully patterns of early onset of anxiety disorders and AN.
Of 637 women with AN, 39% met criteria for
OAD. In this study, the prevalence of OAD varied
across the diagnostic subtypes of AN, with OAD
more common among PAN and ANBN. This finding
is inconsistent with some studies of comorbid anxiety which did not find differences across eating disorder subtypes,2,3 but consistent with others.5 Godart et al.5 found that individuals with RAN and
ANBN were more likely than those with BN to have
a lifetime diagnosis of OCD, and RAN reported significantly higher prevalences of current OCD and
GAD than those with BN. However, in that study,
PAN was not included in the comparisons and
prevalence of childhood anxiety disorders was not
given.
Our findings suggest that women with AN who
engage in purging behaviors are more likely than
those who do not purge to have had OAD in childhood. Strober37 theorized that women with anxiety
disorders and AN may have a similar liability that
manifests as a heightened sensitivity to fear conditioning with resistance to extinction. Applying that
theory, those women with AN who had preexisting OAD may simply be more vulnerable to this
329
RANEY ET AL.
TABLE 2. Means and results from analysis of variance assessing differences in personality variables and
eating disorder attitudes between those with OAD and those without*
Variable
Eating disorder features
ED age of onset
Lowest preferred weight
Highest BMI
Lowest BMI
ED duration
Lowest preferred daily caloric intake (kcal)
Temperament and Character Inventory
Cooperativeness
Harm avoidance
Novelty seeking
Reward dependence
Persistence
Self-directedness
Self-transcendence
Yale-Brown-Cornell Eating Disorder Scale
Worst motivation to change
Worst rituals
Worst preoccupations
Yale-Brown Obsessive Compulsive Scale
Obsessions
Compulsions
Multidimensional Perfectionism Scale
Concern over mistakes
Doubts about actions
Organization
Parental criticism
Parental expectations
Personal standards
Eating Disorders Inventory-2
Body dissatisfaction
Bulimia
Drive for thinness
State-Trait Anxiety Inventory Form Y-1
Trait anxiety
The Revised NEO Personality Inventory
Extraversion
Neuroticism
No OAD, (N 5 388) Mean (SD)
OAD, (N 5 249) Mean (SD)
16.1 (2.7)
37.3 (8.1)
21.3 (2.4)
13.8 (1.9)
8.8 (7.4)
519.0 (328.9)
16.1 (3.0)
36.2 (8.0)
21.4 (2.4)
13.7 (1.9)
10.9 (7.6)
413.6 (290.0)
34.5 (5.6)
20.0 (7.9)
16.4 (7.1)
16.3 (3.9)
6.0 (1.9)
28.4 (8.9)
13.7 (6.8)
35.1 (6.1)
24.2 (6.6)
15.3 (7.0)
16.9 (4.0)
6.5 (1.6)
24.9 (9.0)
14.7 (6.0)
18.6 (5.3)
12.5 (2.6)
12.8 (2.5)
19.1 (5.5)
13.6 (2.3)
13.8 (2.2)
0.18 (.68)
4.33 (.06)
5.65 (.03)
6.6 (6.5)
7.2 (6.7)
10.1 (5.8)
10.7 (6.2)
2.02 (.19)
.056 (.49)
32.2 (9.1)
12.5 (3.8)
25.1 (5.5)
9.9 (4.4)
13.9 (5.7)
28.1 (5.6)
38.1 (6.7)
15.0 (3.4)
25.9 (4.9)
13.0 (4.9)
16.4 (6.0)
30.2 (4.4)
32.27 (\.001)
25.56 (\.001)
2.59 (.15)
36.24 (\.001)
11.61 (.003)
11.93 (.003)
17.1 (7.0)
2.6 (4.4)
14.6 (5.9)
20.3 (6.8)
4.3 (5.5)
16.9 (5.1)
11.42 (.003)
11.31 (.003)
10.22 (.004)
50.4 (13.0)
58.3 (12.8)
28.74 (\.001)
105.7 (22.1)
105.7 (25.3)
98.9 (22.7)
120.8 (21.7)
5.34 (.04)
10.13 (\.001)
F-Value (p-Value)
0.19 (.68)
0.48 (.51)
0.91 (.39)
0.00 (.95)
7.90 (.01)
4.21 (.06)
2.18 (.82)
17.23 (\.001)
5.86 (.03)
3.24 (.10)
9.36 (.006)
7.81 (.01)
0.60 (.48)
*The presence or absence of any other anxiety disorder was entered into all models as a covariate. Eating disorder subtype was also entered as a covariate for all models except those predicting eating disorder features.
TABLE 3.
Frequency of anxiety disorders by presence or absence of a history of OAD: % (N)*
Prevalence of Anxiety Disorders
Agoraphobia
Generalized anxiety Disorder
Panic disorder
Obsessive compulsive Disorder
Social phobia
Specific phobia
Means (std) Age of Onset of Anxiety Disorders
No OAD
OAD
v2 (p-Value)
No OAD
OAD
t-Score (p-Value)
2.3 (9)
7.2 (28)
10.1 (39)
42.9 (165)
13.5 (52)
5.4 (21)
3.7 (11)
25.9 (64)
18.6 (46)
68.8 (170)
33.9 (83)
15.5 (38)
0.94 (.33)
42.58 (\.001)
9.33 (.002)
40.74 (\.001)
37.11 (\.001)
17.84 (\.001)
15.8 (8.0)
15.6 (6.7)
20.6 (6.8)
13.6 (5.6)
12.5 (4.8)
8.7 (6.9)
21.3 (8.3)
11.3 (6.7)
19.4 (8.8)
11.1 (5.9)
10.8 (4.8)
9.3 (7.2)
21.30 (.25)
2.79 (.01)
0.70 (.49)
3.78 (\.001)
1.95 (.07)
20.28 (.80)
*Comparison made by chi-square. Also, means (std) of age of onset of anxiety disorders by presence or absence of a history of OAD.
excessive fear conditioning, have more intense anxiety responses, and turn to purging as an immediate intervention to reduce the extreme emotional
distress. An alternative explanation is that those
women with OAD may have a generalized heightened sensitivity to fear conditioning that, with the
emergence of AN, is complicated by the addition of
a ‘‘weight based’’ specific fear. The additive impact
330
of the general and specific foci for the extreme fear
conditioning may result in a more intense perceived
need to reduce anxiety through purging. Another
possible explanation is that anxious symptoms may
be related to altered striatal dopamine function in
AN.38 Sustained activation of dopamine neurons is
related to uncertainty.39 Perhaps a contributing
component of anxiety in AN individuals is a heightInternational Journal of Eating Disorders 41:4 326–332 2008
OAD OF CHILDHOOD AND AN
ened sensitivity to uncertainty, resulting in extreme
distress reduction strategies such as purging.
The presence of OAD in this sample was associated with a more severe and complex clinical presentation. Previous research has not consistently
demonstrated a relationship between anxiety disorders and increased severity of eating disorder
symptoms.40 In contrast, our explicit focus on OAD
with onset by definition in childhood identified a
consistent and robust association between anxiety
and severity of eating disorder symptoms and
personality traits. Although all women with AN
displayed the characteristic personality profiles
expected in this population (e.g., harm avoidance,
persistence, perfectionism, and lower self-directedness), those with a history of OAD displayed a profile that was magnified. The same pattern held for
eating disorder behaviors, with those with a history
of OAD engaging in more problematic weight control practices and displaying greater body dissatisfaction, higher drive for thinness, more eating preoccupation, and longer duration of illness.
OAD was also associated with the presence of
additional anxiety disorders. As may be expected,
those individuals with a history of OAD were significantly more likely to have GAD, OCD, specific phobia, social phobia, and panic disorder. Agoraphobia
was infrequently endorsed by participants and did
not differ significantly between women with or
without OAD. The presence of OAD was also associated with younger ages of onset for GAD and
OCD than those without OAD who developed these
conditions. Collectively, these observations suggest
that childhood OAD is a pernicious disorder that is
associated with greater severity and longer duration of eating disorder.
The results of this investigation should be viewed
within the context of several limitations. The OAD
diagnoses and age at onset estimates were made
retrospectively and subject to recall biases inherent
in that approach. Individuals with anxiety disorders
persisting into adulthood or who developed additional anxiety disorders later in life may have been
more sensitized to recognize anxiety symptoms in
childhood which could inflate the association
between childhood onset and other anxiety disorders. Another limitation is that the SCID assesses
only current GAD, so many cases of remitted GAD
are missed. Therefore, many participants may, at
an earlier time, have met criteria for GAD and
would have gone undetected if the GAD had remitted at the time of assessment. Furthermore, the
SCID screen for GAD is limited in that people who
are always anxious may not report having been
more anxious in the past 6 months. One of the
International Journal of Eating Disorders 41:4 326–332 2008
strengths of studying OAD is that it captures those
individuals with an early pervasive anxiety, even if
the symptoms remitted at the time of assessment.
In addition, the distinction of OAD as a diagnosis
of childhood is somewhat artificial as many of the
patients reported the onset of other anxiety disorders close in time to their childhood anxiety disorder. In the DSM-IV41 the diagnosis of OAD was subsumed by the diagnosis of GAD, with the only
remaining distinction being that children can present with fewer symptoms to meet diagnostic criteria.
Also noteworthy, this study is part of multicenter
genetic study, so the participants were recruited
from populations of primarily European descent to
ensure sample homogeneity that is critical in genetic
studies. This homogeneity limits the generalizability
of these findings to non-European groups.
An OAD pathway may represent one entrée into
AN, which portends persistent and pervasive
anxious symptoms, obsessive and perfectionistic
personality styles, and later anxiety disorders.
Although these observations are based on retrospective recall, they highlight the importance of
early detection of OAD as a potential means of
averting the emergence of both later anxiety and
eating disorders symptoms.
Support for the clinical collection of participants and data
analysis was provided by the Price Foundation. The
authors thank the staff of the Price Foundation Collaborative Group for their efforts in participant screening and
clinical assessments and the participating families for their
contribution of time and effort in support of this study.
This study was also supported by grant MH-66117 from
the National Institutes of Health, Bethesda, MD.
References
1. Godart NT, Flament MF, Perdereau F, Jeammet P. Comorbidity
between eating disorders and anxiety disorders: A review.
International J Eat Disord 2002; 32:253–270.
2. Kaye WH, Bulik CM, Thornton L, Barbarich N, Masters K, the
Price Foundation Collaborative Group. Comorbidity of anxiety
disorders with anorexia and bulimia nervosa. Am J Psychiatry
2004;161:2215–2221.
3. Blinder B, Cumella E, Sanathara V. Psychiatric comorbidities of
female inpatients with eating disorders. Psychosom Med
2006;68:454–462.
4. Godart N, Berthoz S, Perdereau F, Jeammet P. Comorbidity of
anxiety with eating disorders and OCD. Am J Psychiatry
2006;163:326.
5. Godart N, Berthoz S, Rein Z, Perdereau F, Lang F, Venisse J-L,
et al. Does the frequency of anxiety and depressive disorders
differ between diagnostic subtypes of anorexia nervosa and
bulimia? Int J Eat Disord 2006;39:772–778.
6. Bulik C, Sullivan P, Fear J, Joyce P. Eating disorders and antecedent anxiety disorders: a controlled study. Acta Psychiatr Scand
1997;96:101–107.
331
RANEY ET AL.
7. Deep AL, Nagy LM, Weltzin TE, Rao R, Kaye WH. Premorbid onset
of psychopathology in long-term recovered anorexia nervosa. Int J
Eat Disord 1995;17:291–297.
8. Pollice C, Kaye WH, Greeno CG, Weltzin TE. Relationship of
depression, anxiety, and obsessionality to state of illness in anorexia nervosa. Int J Eat Disord 1997;21:367–376.
9. Kendler KS. Twin Studies of psychiatric illness: An update. Arch
Gen Psychiatry 2001;58:1005–1014.
10. Bulik CM, Sullivan PF, Wade TD, Kendler KS. Twin studies of
eating disorders: A review. Int J Eat Disord 2000;27:1–20.
11. Bulik CM, Sullivan PF, Tozzi F, Furberg H, Lichtenstein P, Pedersen NL. Prevalence, heritability, and prospective risk factors for
anorexia nervosa. Arch Gen Psychiatry 2006;63:305–312.
12. Klump K, Miller K, Keel P, McGue M, Iacono W. Genetic
and environmental influences on anorexia nervosa syndromes
in a population-based twin sample. Psychol Med 2001;31:737–
740.
13. Wade TD, Bulik CM, Neale M, Kendler KS. Anorexia nervosa and
major depression: Shared genetic and environmental risk factors. Am J Psychiatry 2000;157:469–471.
14. Keel PK, Klump KL, Miller KB, McGue M, Iacono WG. Shared
transmission of eating disorders and anxiety disorders. Int J Eat
Disord 2005;38:99–105.
15. Silberg JL, Bulik CM. The developmental association between
eating disorders symptoms and symptoms of depression and
anxiety in juvenile twin girls. J Child Psychol Psychiatry 2005;46:
1317–1326.
16. Hebebrand J, Himmelmann GW, Heseker H, Schäfer H, Remschmidt
H. Use of percentiles for the body mass index in anorexia nervosa:
Diagnostic, epidemiological, and therapeutic considerations. Int
J Eat Disord 1996;19:359–369.
17. Bulik C, Sullivan P, Fear J, Pickering A. Predictors of the development of bulimia nervosa in women with anorexia nervosa.
J Nerv Ment Dis 1997;185:704–707.
18. Eckert E, Halmi K, Marchi P, Grove W, Crosby R. Ten-year follow-up of anorexia nervosa: Clinical course and outcome. Psychol Med 1995;25:143–156.
19. Strober M, Freeman R, Morrell W. The long-term course of
severe anorexia nervosa in adolescents: Survival analysis of recovery, relapse, and outcome predictors over 10–15 years in a
prospective study. Int J Eat Disord 1997;22:339–360.
20. Eddy KT, Keel PK, Dorer DJ, Delinsky SS, Franko DL, Herzog DB.
Longitudinal comparison of anorexia nervosa subtypes. Int
J Eat Disord 2002;31:191–201.
21. Tozzi F, Thornton LM, Klump KL, Fichter MM, Halmi KA, Kaplan
AS, et al. Symptom fluctuation in eating disorders: Correlates of
diagnostic crossover. Am J Psychiatry 2005;162:732–740.
22. Lilenfeld LR, Kaye WH, Greeno CG, Merikangas KR, Plotnicov K,
Pollice C, et al. A controlled family study of anorexia nervosa
and bulimia nervosa: Psychiatric disorders in first-degree relatives and effects of proband comorbidity. Arch Gen Psychiatry
1998;55:603–610.
23. Fichter MM, Herpertz S, Quadflieg N, Herpertz-Dahlmann B.
Structured interview for anorexic and bulimic disorders for
DSM-IV and ICD-10: Updated (third) revision. Int J Eat Disord
1998;24:227–249.
332
24. First M, Spitzer R, Gibbon M, Williams J. Structured Clinical
Interview for DSM-IV Axis I Disorders, Research Version, Patient
Edition. New York: New York State Psychiatric Institute, 1997.
25. Kaye WH, Devlin B, Barbarich N, Bulik CM, Thornton L, Bacanu
S-A, et al. Genetic analysis of bulimia nervosa: Methods and
sample description. Int J Eat Disord 2004;35:556–570.
26. Garner DM. Eating Disorder Inventory-2 Professional Manual.
Odessa, FL: Psychological Assessment Resources, 1991.
27. Merikangas KR, Stevens D, Fenton B, Stolar M, O’Malley S,
Woods S, et al. Co-morbidity and familial aggregation of alcoholism and anxiety disorders. Psychol Med 1998;28:773–788.
28. Puig-Antich J, Orvaschel H, Tabrizi M, Chambers W. The Schedule for Affective Disorders and Schizophrenia for School-Age
Children—Epidemiologic Version (Kiddie-SADS-E), 3rd ed. New
York: New York State Psychiatric Institute and Yale University
School of Medicine, 1980.
29. Cloninger CR, Przybeck TR, Svrakic DM, Wetzel RD. The Temperament and Character Inventory (TCI): A guide to its Development and Use. St. Louis, MO: Washington University Press,
1994.
30. Frost RO, Marten P, Lahart C, Rosenblate R. The dimensions of
perfectionism. Cogn Ther Res 1990;14:449–468.
31. Spielberger C, Gorsuch R, Luchene R. STAI manual for the StateTrait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists
Press, 1970.
32. Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann
RL, Hill CL, et al. The Yale-Brown obsessive compulsive scale. I.
Development, use, and reliability. Arch Gen Psychiatry 1989;46:
1006–1011.
33. Sunday SR, Halmi KA. Comparison of the Yale-Brown-Cornell
eating disorders scale in recovered eating disorder patients,
restrained dieters, and nondieting controls. Int J Eat Disord
2000;28:455–459.
34. Costa PTJ, McCrae RR. NEO PI-R: Professional manual. Odessa,
FL: Psychological Assessment Resources, 1992.
35. SAS Institute. SAS/STAT1 Software: Version 9. Cary, NC: SAS
Institute, 2004.
36. Benjamini Y, Hochberg Y. Controlling the false discovery rate: A
practical and powerful approach to multiple testing. J R Stat
Soc Ser B 1995;57:289–300.
37. Strober M. Clinical and research forum pathologic fear conditioning and anorexia nervosa: On the search for novel paradigms. Int J Eat Disord 2004;35:504–508.
38. Frank GK, Bailer UF, Henry SE, Drevets W, Meltzer CC, Price JC,
et al. Increased Dopamine D2/D3 receptor binding after recovery from anorexia nervosa measured by positron emission tomography and [11C]Raclopride. Biol Psychiatry 2005; 58:908–912.
39. Fiorillo CD, Tobler PN, Schultz W. Discrete coding of reward
probability and uncertainty by dopamine neurons. Science 2003;
299:1898–1902.
40. Saccomani L, Savoini M, Cirrincione M, Vercellino F, Ravera G.
Long-term outcome of children and adolescents with anorexia
nervosa: Study of comorbidity. J Psychosom Res 1998;44:565–571.
41. American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders, 4th ed. Washington, DC: American
Psychiatric Association Press, 1994.
International Journal of Eating Disorders 41:4 326–332 2008