Anxiety and Psychoactive Substance Use DisorderComorbidity in Anorexia Nervosa or Depression

Jennifer Jordan,1* Peter R. Joyce,1 Frances A. Carter,1 Jacqueline Horn,1

Virginia V. W. McIntosh,1 Suzanne E. Luty,1 Janice M. McKenzie,1

Roger T. Mulder,1 and Cynthia M. Bulik2

1 Department of Psychological Medicine, Christchurch School of Medicine andHealth Sciences, University of Otago, Christchurch, New Zealand

2 Department of Psychiatry, Virginia Commonwealth University, Medical Collegeof Virginia Campus, Richmond, Virginia

Accepted 5 June 2002

Abstract: Objective: This study considered whether the prevalence and type of anxiety andpsychoactive substance use disorder (PSUD) diagnoses differ between women with spectrumanorexia nervosa (AN) (N¼ 40) and women with major depressive disorder (N ¼ 58)participating in outpatient clinical trials. Method: Anxiety and PSUD diagnoses (accordingto criteria in the 3rd Rev. ed. of the Diagnostic and Statistical Manual of Mental Disorders)were assessed using structured clinical interviews. Comparisons were made between ANsubtypes (restricting or binge eating/purging) and by history of depression within the ANsample. Results: A high prevalence of obsessive-compulsive disorder (OCD) was found inwomen with AN. However, social phobia, simple phobia, and PSUD were significantlyelevated in both women with depression and women with AN. Prevalences were similar foranxiety and PSUD diagnoses between AN subtypes. Discussion: Women with anorexia ordepression were comparable in all respects, except for the elevated OCD prevalence in AN,emphasizing the need to use clinical comparison groups to avoid inadvertently attributingelevated prevalences of comorbid conditions to specific disorders. # 2003 by Wiley Period-icals, Inc. Int J Eat Disord 34: 211–219, 2003.

Key words: anxiety; psychoactive substance use disorder; comorbidity; anorexia nervosa;depression

INTRODUCTION

Psychiatric comorbidity is common. In epidemiologic studies, approximately one halfof the individuals with any given psychiatric disorder have at least one additionalpsychiatric disorder (Clark, Watson, & Reynolds, 1995). Studying comorbidity may

*Correspondence to: Jennifer Jordan, M.A., Department of Psychological Medicine, Christchurch School ofMedicine and Health Sciences, P.O. Box 4345, Christchurch, New Zealand. E-mail: jenny.jordan@chmeds.ac.nz

Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/eat.10177

# 2003 by Wiley Periodicals, Inc.

contribute to understanding the etiology and nature of disorders. This approach mayhelp to identify eating disorder subtypes and may determine whether comorbidity hasimplications for treatment and outcome (Maser & Cloninger, 1990; Robins, Locke, & Regier,1991). Numerous methodologic issues confound a clear understanding of the relationshipsand strength of associations of comorbid disorders and have contributed to the highlyvariable prevalences reported.

Individuals with anorexia nervosa (AN) have high prevalences of mood and anxietydisorders (Bulik, 1995; Kaye, Weltzin, & Hsu, 1993b). Elevated prevalences of obsessive-compulsive disorder (OCD; about 16%) have been reported by Bulik, Sullivan, Fear, andJoyce (1997). Highly variable rates have been reported for panic disorder (Herzog, Keller,Sacks, Yeh, & Lavori, 1992; Toner, Garfinkel, & Garner, 1988), simple phobia (Sullivan,Bulik, Fear, & Pickering, 1998), and social phobia (Halmi et al., 1991; Sullivan et al., 1998;Wentz, Gillberg, Gillberg, & Rastam, 2001).

Reported prevalences of psychoactive substance use disorder (PSUD) also vary widely(Fairburn, Cooper, Doll, & Welch, 1999; Holderness, Brooks, & Warren, 1994; Sullivan et al.,1998; Walters & Kendler, 1995; Wentz et al., 2001). Several studies have found a higherprevalence of substance abuse in women with the binge eating/purging subtype (AN-BEP)than with the restricting subtype (AN-R; Holderness et al., 1994).

In individuals with depression, elevated prevalences of anxiety (particularly socialphobia and panic) and substance misuse have been noted. A previous New Zealand studyreported elevated prevalences of panic disorder (20%) and alcohol abuse/dependence(22%) in a depressed clinic sample (Sullivan et al., 1996).

The purpose of the current study was to establish whether women with AN differ fromwomen with depression in the prevalence of anxiety and PSUD diagnoses. It washypothesized that the AN sample would have higher prevalences of anxiety disordersbut lower prevalences of PSUD diagnoses (with the AN-R women having the lowestprevalence of PSUD diagnoses) compared with the sample of women with depression.

METHODS

Participants

AN SampleThis study comprised the first 40 women (age range, 17–40 years) who were recruited

into the Christchurch Anorexia Nervosa Treatment Study (McIntosh et al., in press). Thisis a randomized clinical trial of outpatient psychotherapies that compares cognitive-behavior therapy, interpersonal psychotherapy, and a comparison therapy. Recruitmentwas broad based, with self-referral and referrals from health professionals.

Participants met criteria for current ‘‘spectrum’’ AN, which included women with‘‘strict’’ or ‘‘lenient’’ AN. These criteria were defined in the 4th ed. of the Diagnosticand Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association[APA], 1994). Lenient AN extended the weight criterion to include underweight womenwho were deliberately maintaining a low weight (17.6 < 19 body mass index [BMI];modified Criterion A) and who had DSM-IV psychological features of AN (Criteria B andC). For women with both strict and lenient AN, the amenorrhea criterion (Criterion D)was not necessary for inclusion in the study, given the recent debate in the literatureconcerning the necessity of this criterion (Cachelin & Maher, 1998). A previous analysisof this sample (McIntosh et al., in press) found few differences between strict and lenient

212 Jordan et al.

subgroups on a range of variables including demographic data, measures of eatingdisorder behaviors and cognitions, physical measures, and anxiety or psychoactive sub-stance use comorbidity. For the purposes of this study, use of the term AN includes bothstrict and lenient diagnoses.

Exclusion criteria were current severe major depression or serious suicidal intent,cognitive impairment, bipolar I disorder, schizophrenia, severe physical illness, severemedical complications of AN, or a primary diagnosis of current severe psychoactivesubstance dependence.AN Subtypes The AN sample was split into two subtypes: AN-R (n ¼ 24) and AN-BEP(n ¼ 16). This was based on DSM-IV criteria, that is, regular binge eating or purgingoperationalized as 12 or more episodes in the last 3 months.Depressed and Not-Depressed AN Subgroups The AN sample was divided into an AN-depressed group (n ¼ 25) and an AN-not-depressed group (n ¼ 15), based on thepresence or absence of lifetime major depressive disorder (MD; according to criteria inthe 3rd Rev. ed. of the Diagnostic and Statistical Manual of Mental Disorders [DSM-III-R;APA, 1987).

Depression SampleThis sample comprised 58 women (age range, 18–40 years) who were recruited for the

Outcome of Depression Study (Luty, Joyce, Mulder, Sullivan, & McKenzie, 1998). Thisincluded all women within the age range of the AN sample but excluded those witha past or current diagnosis of AN or bulimia nervosa. Women with a score of 14 or higheron the Hamilton Rating Scale for Depression Scale (HRSD; Hamilton, 1986) met thecriteria for current MD. Exclusion criteria were bipolar I or II disorder, significantmedical illness, or current severe alcohol or drug dependence as a primary diagnosis.Recruitment included referrals from general practitioners, other psychiatrists, or mentalhealth services.

Both treatment trials had received ethical approval and all participants had providedwritten consent.

Measures

Information collected included demographic details, onset of the index condition,number of comorbid conditions, psychiatric history, and current functioning. The PatientVersion of the Structured Clinical Interview for DSM-III-R (SCID-P; Spitzer, Williams,Gibbon, & First, 1992) was administered at baseline by trained clinical interviewers todetermine the presence of lifetime mood, anxiety, and PSUDs. The SCID was expandedto include sections of the Schedule for Affective Disorders and Schizophrenia (SADS-L)developed by Dr. Kathleen Merikangas (Yale University; personal communication) toassess childhood anxiety disorders (separation anxiety disorder and overanxious dis-order). These additional modules were used by Bulik et al. (1997).

The 17-item HRSD was used as a measure of the severity of depression. The GlobalAssessment of Functioning (GAF) provided a clinician-rated measure of psychosocialfunctioning in the last week. It was modified for the AN sample by the addition ofstatements relevant to AN or eating disorder severity to make scoring easier and moreobjective. The Hopkins Symptom Checklist (SCL-90; Derogatis, 1973) provided a self-report measure of psychological distress and psychopathology (past week).

Anxiety and Substance Use in AN Patients 213

RESULTS

Characteristics of the Samples

Table 1 details demographic, psychiatric history, and current functioning informationfor the AN and MD samples. Despite the age range for inclusion being similar, there wasa significant difference between the mean ages of the samples, with the AN sample beingyounger. However, the mean age of onset of the index condition (AN or depression) wasnot significantly different. More of the AN sample reported previous treatment for anypsychiatric disorder than the MD sample. There were no significant differences betweentotal scores on the SCL-90 and the GAF, suggesting similar levels of current distress andimpaired function, respectively, regardless of the presenting problem.

Anxiety and PSUD Comorbidity

AN Sample versus MD SampleTable 2 shows the prevalence of lifetime and current DSM-III-R anxiety disorders,

childhood anxiety disorders, and PSUD diagnoses in the AN and MD samples. The ANsample had a higher prevalence of lifetime OCD, with an odds ratio of 18.3. There wereno other significant differences for other lifetime anxiety disorders, including childhoodanxiety or any lifetime anxiety disorders, or for prevalences of PSUD diagnoses.

Number of Comorbid ConditionsThe AN sample had significantly more DSM-III-R anxiety diagnoses than the MD

sample (AN: median ¼ 1.0, range ¼ 0–3; MD: median ¼ 0, range ¼ 0–3; Mann–WhitneyU test ¼ 9994.50, p < .05). The number of PSUD diagnoses did not differ betweensamples.

Table 1. Characteristics of women in the AN and MD samples

Variables AN (n ¼ 40) MD (n ¼ 58) df Statistics p

DemographicAge 23.15 (6.69) 26.48 (6.5) 96 �2.48a <.05Caucasian 98% 93% –b nsMarital statusNever married 63% 60% .05c nsMarried/de facto 28% 28%Other 10% 12%

Psychiatric historyAge of onset 17.23 (5.67) 18.60 (7.25) 96 �1.00a nsPrevious treatment 60% 33% 7.13c <.05Previous suicide attempt 23% 36% 2.09c ns

Current functioningGAF 48.85 (5.82) 52.00 (7.64) 96 �2.20a <.05HRSD score 12.40 (6.96) 19.05 (4.12) 96 �5.93a <.05SCL-90 12.97 (6.16) 12.03 (5.19) 95 �.81a ns

Note: AN ¼ anorexia nervosa; MD ¼ major depressive disorder; GAF ¼ Global Assessment of Functioning;HRSD ¼ Hamilton Rating Scale for Depression; SCL-90 ¼ Symptom Checklist.

a t-test.b Fisher’s exact test.c Chi-square test.

214 Jordan et al.

AN Subtypes

Depressed/Not-Depressed (Lifetime)Table 3 shows lifetime DSM-III-R anxiety and PSUD prevalences in the lifetime

AN-depressed and AN-not-depressed groups. The AN-depressed group had a greaterprevalence of any lifetime anxiety diagnosis than the AN-not-depressed group (p < .05).There were no other significant differences in lifetime anxiety or PSUD disorders basedon this subgrouping. Women in the AN sample with current depression (n ¼ 18 [45%])were compared with the women without current depression. The currently depressedgroup had a significantly greater prevalence of lifetime social phobia (AN-currentlydepressed, 50%; AN-not currently depressed, 18%; �2 ¼ 4.57, p < .05) and current socialphobia (AN-currently depressed, 44%; AN-not currently depressed, 13.6%; Fisher’s exacttest, p < .05).

AN-R versus AN-BEP

There were no significant differences between women with the AN-R and AN-BEPsubtypes in terms of demographics, psychiatric history variables, or any of the anxiety orPSUD diagnoses (Table 3).

DISCUSSION

This study addressed whether women with AN differ from women with MD in theprevalences of anxiety and PSUD. Unlike previous reported studies in this area, thepresence of a history of comorbid depression in the AN sample was taken into account todetermine whether this might influence observed differences. Apart from the small butstatistically significant age difference, the groups were very similar in terms of demog-raphy, psychiatric history, current psychological distress, and psychosocial impairment.

Table 2. Lifetime anxiety and PSUD in the AN and MD samples

AN (n ¼ 40) MD (n ¼ 58)

Diagnosis (Lifetime) n % n % ORa CI p

OCD 9 23 1 2 16.5 2.00–136.74 <.05Panic and/or agoraphobia 5 12 5 9 1.51 .41–5.62 nsSocial phobia 13 33 12 21 1.85 .74–4.62 nsSimple phobia 11 28 8 14 2.37 .86–6.57 nsAny anxiety

Lifetime 21 53 24 41 1.57 .70–3.52 nsCurrent 15 38 20 35 1.14 .49–2.64 ns

Separation anxietyb 3 8 5 9 0.88 .19–3.93 nsOveranxious disorderb 6 15 10 17 0.87 .29–2.64 nsAlcohol abuse or dependence 11 28 15 26 1.09 .44–2.70 nsCannabis abuse or dependence 8 20 9 16 1.36 .48–3.90 nsAny PSUD

Lifetime 13 33 15 26 1.38 .57–3.34 nsCurrent 3 8 5 9 0.86 .19–3.82 ns

Note: AN ¼ anorexia nervosa; MD ¼ major depressive disorder; OR ¼ odds ratio; CI ¼ confidence interval;OCD ¼ obsessive-compulsive disorder; PSUD ¼ psychoactive substance use disorder.

a OR calculated relative to depression sample.b Data are missing for 1 AN participant (n ¼ 39).

Anxiety and Substance Use in AN Patients 215

Tab

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of

AN

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AN

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135.

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303

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257

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130

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131

43.

54.2

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522

17

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34.6

9n

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203

131.

75.3

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40n

s

Can

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or

dep

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ence

522

320

1.11

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5.54

ns

531

313

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.64–

15.8

6n

s

An

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ime

730

427

1.20

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ns

638

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1.46

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5.57

ns

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rren

t2

91

71.

33.1

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.14

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are

mis

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216 Jordan et al.

The similarity of these samples allows comparison of the relative prevalence and patternsof comorbidity.

The finding of a statistically significant higher prevalence of OCD in the AN sample isconsistent with the existing literature. This repeated finding, despite variation in samples,demonstrates the robustness of the association between OCD and AN. Obsessionaltendencies frequently predate AN (Bulik et al., 1997; Speranza et al., 2001), persistregardless of eating disorder status (Pollice, Kaye, Greeno, & Weltzin, 1997; The PriceFoundation Collaborative Group, 2001; Wentz et al., 2001), and are associated withpoorer outcome, especially psychosocial functioning (Wentz et al., 2001).

Theories of serotonin dysregulation (both state and trait) have been proposed toaccount for the strong association between OCD and AN (Kaye, 1997). There is consider-able evidence linking serotonin to alterations in eating, mood, anxiety, and to OCD(Brewerton & Jimerson, 1996; Kaye & Weltzin, 1991; Kaye, Weltzin, & Hsu, 1993a). Forindividuals with comorbid OCD and AN, examination of serotonin dysregulation mayprovide important etiologic insights as well as promising clinical implications.

The AN and MD samples demonstrated similar elevated prevalences of having anylifetime anxiety disorder. However, the median number of anxiety disorders in the ANsample was higher than for the MD sample. This supports many previous reports ofanxiety being a prominent comorbid feature of AN (Bulik, 1995).

Although the rate of social phobia in the whole AN sample was not significantlydifferent to the MD group, the obtained prevalence rate was higher than in a previousstudy (Sullivan et al., 1998). However, the study does show a clear difference betweenindividuals in the AN sample with or without current depression. Individuals with ANwho were currently depressed were significantly more likely to have social phobia thanthe not-currently-depressed AN group. Failure by other studies to account for the pres-ence of depression might explain the variable prevalences of social phobia previouslynoted in the AN literature.

Prevalences of lifetime and current PSUD diagnoses were similarly elevated in bothsamples compared with epidemiologic samples (Robins et al., 1991). One explanation forthe higher rate in the AN sample might be that this community clinical sample is morelikely to abuse substances recreationally than inpatient samples with more severe AN.The finding of no significant difference in PSUD prevalences between AN-R and AN-BEPcontrasts with those studies reporting higher prevalences in the bulimic subtype of AN.

Future research should evaluate the possibility of tailoring treatment packages forthis subgroup of persons with comorbid OCD and AN to improve outcome (Nilsson,Gillberg, Gillberg, & Rastam, 1999). Such treatments may need to address the comorbidanxiety disorder and the eating disorder concurrently, placing more explicit emphasis onthe use and generalization of techniques from the anxiety management field, possibly inconjunction with the use of serotonergic medications.

Methodologic issues to be considered when interpreting this study are as follows: Allparticipants were women; clinical samples were included (potentially inflating comor-bidity rates); and the small AN sample combined with the low base rate is likely to limitthe power to detect differences. Sampling and exclusion criteria resulted in the ANsample having less severe AN, possibly affecting patterns of comorbidity. There arepotential problems when evaluating the percentages of PSUD diagnoses when womenwith a primary current, severe PSUD were excluded from the study. However, for bothstudies, there were no exclusions solely on this basis.

In conclusion, differences were found in the pattern of anxiety disorders. For example,the AN sample had more OCD and more anxiety diagnoses than the depression sample,

Anxiety and Substance Use in AN Patients 217

a finding with significant clinical implications. In addition, the similarities between theAN and depression sample were more salient than their differences. In both samples,anxiety and PSUD were very common. This reinforces the need to compare the clinicalsample of interest with other clinical comparison groups to avoid spurious claims aboutthe significance of elevated prevalences of comorbid disorders, thereby removing onearea of methodologic confusion in the comorbidity literature. These findings also raiseother questions regarding models of etiology, and common predisposing factors tononspecific pathology, as well as to predictable associations.

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Anxiety and Substance Use in AN Patients 219