Research Report

RESEARCH ARTICLE Open Access

Long-term disability in anxiety disorders Sanne M. Hendriks1*, Jan Spijker2, Carmilla M. M. Licht3, Florian Hardeveld4, Ron de Graaf5, Neeltje M. Batelaan3, Brenda W. J. H. Penninx3 and Aartjan T. F. Beekman3

Abstract

Background: This longitudinal study aims to investigate differences in long-term disability between social anxiety disorder (SAD), panic disorder with agoraphobia (PDA), panic disorder without agoraphobia (PD), generalized anxiety disorder (GAD) and multiple anxiety disorders (multiple AD), focusing on the effects of different course trajectories (remission, recurrence and chronic course) and specific symptom dimensions (anxiety arousal and avoidance behaviour).

Methods: Data were used from participants with no psychiatric diagnosis (healthy controls, n = 647) or with a current anxiety disorder (SAD, n = 191; PDA, n = 90; PD, n = 84; GAD, n = 110; multiple AD, n = 480). Severity of anxiety arousal and avoidance behaviour symptoms was measured using the Beck Anxiety Inventory and the Fear Questionnaire. The World Health Organization Disability Assessment Schedule II was used to measure disability.

Results: Long-term disability was most prevalent in participants with SAD and multiple AD, and lowest in PDA and PD. GAD had an intermediate position. Anxiety arousal and avoidance behaviour were associated with more long-term disability in anxiety disorders than course trajectories.

Conclusions: Various anxiety disorders have different disability levels over 4 years of time, therefore diagnostic distinction is important for treatment focus. Anxiety arousal and avoidance behaviour are major predictors for long-term disability in anxiety disorders.

Background Disability is often defined as ‘any restriction or lack of capacity to perform an activity in a manner or within a range considered normal for a human being’ [1]. Anxiety disorders are associated with severe disability [2–6] and the negative impact of anxiety is substantial [3, 7, 8]. Previous research showed that anxiety disorders differ in disability levels. Overall, multiple anxiety disorders (mul- tiple AD, i.e. comorbidity with other anxiety disorders) are associated with more disability than pure anxiety dis- orders [9]. Furthermore, social anxiety disorder (SAD) and generalized anxiety disorder (GAD) are associated with higher disability levels compared to panic disorder, [3, 10–12] although other research points out otherwise [13–15]. However, it remains unclear whether contrasts

in disability levels among anxiety disorders persist over a longer period. More severe symptoms and more comorbidity are associ-

ated with a chronic course in anxiety disorders [16–20]. Therefore, we expect that long-term disability is more com- mon in anxiety patients with a chronic course. However, some research gave indications that disability can still be present after remission of the anxiety disorder [21]. Because SAD and multiple AD are more strongly associated with a chronic course than other anxiety disorders [19, 22–24] we expect that long-term disability therefore is more prevalent in SAD and multiple AD. Furthermore, previous research showed that symptom

dimensions, like anxiety arousal and avoidance behaviour, can be strong predictors [19, 20, 25]. Hendriks et al. [19] showed that avoidance behaviour symptoms may be more important predictors than the symptoms of anxiety itself. This would lead to the hypothesis that long-term disability is more frequently seen in panic disorder with agorapho- bia (PDA) and SAD compared to panic disorder without agoraphobia (PD) and GAD because of the high levels of avoidance behaviour in PDA and SAD.

* Correspondence: [email protected] 1Department of Psychiatry, Pro Persona Mental Health Care, Zandstraat 54, Veenendaal 3905 ED, The Netherlands Full list of author information is available at the end of the article

© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Hendriks et al. BMC Psychiatry (2016) 16:248 DOI 10.1186/s12888-016-0946-y

This longitudinal study among a large cohort of partici- pants with anxiety disorders investigates: 1) differences in long-term disability between participants with social anxiety disorder (SAD), panic disorder with agoraphobia (PDA), panic disorder without agoraphobia (PD), generalized anx- iety disorder (GAD) and multiple anxiety disorders (mul- tiple AD); 2) differences in long-term disability for different course trajectories; and 3) the role of anxiety arousal and avoidance behaviour in long-term disability.

Methods Study sample As reported before, [11, 19, 20]. The Netherlands Study of Depression and Anxiety (NESDA) is a naturalistic co- hort study to examine the long-term course and conse- quences of anxiety and depressive disorders [26]. In short, a total of 2981 participants were included, aged 18 through 65 years. The research protocol was approved centrally by the ethical review board of VU University Medical Center. Subsequently it was approved by the local ethical review boards of Leiden University Medical Center and University Medical Center Groningen. The study was performed in accordance with the ethical standards of the Declaration of Helsinki. All participants provided written informed con- sent. Participants with a current or lifetime diagnosis of anxiety or depression, and healthy controls were included. Exclusion criteria were (1) a primary diagnosis of psych- otic, obsessive compulsive, bipolar or severe addiction dis- order, and (2) not being fluent in Dutch. Participants with an anxiety disorder (SAD, PDA, PD,

GAD and multiple AD) at baseline (6-month recency

diagnosis) and healthy controls were included for this study (Fig. 1). A follow-up assessment was done two (T1) and 4 years (T2) after the baseline measurement. In total 1602 participants met these criteria at T0 (baseline); 191 partici- pants (11.9 %) with pure SAD, 90 participants (5.6 %) with pure PDA, 84 participants (5.2 %) with pure PD, 110 par- ticipants (6.9 %) with pure GAD, 480 participants (30.0 %) with multiple AD and 647 healthy controls (40.4 %). 1351 participants (84.3 %) had a follow-up assessment at T1, and 1235 participants (77.1 %) at T2.

Psychiatric status As done before, [11, 19, 20] the Composite International Diagnostic Interview (CIDI version 2.1) was used to diagnose the presence of SAD, PDA, PD, GAD and mul- tiple AD, a highly reliable and valid instrument for asses- sing anxiety disorders [27].

Course trajectory The clinical course trajectory categorized the participants into four groups: a) healthy controls (no history of anxiety disorder and no anxiety disorder at T0, T1 and T2), b) re- mission (remission of baseline anxiety disorder at T1 and/ or T2 without recurrence), c) recurrence (remission of baseline anxiety disorder at T1 but with recurrence at T2), and d) chronic course (baseline anxiety disorder at T0, T1 and T2).

Anxiety arousal and avoidance behaviour As done before, [11, 19, 20] the Beck Anxiety Inventory (BAI) [28] and the Fear Questionnaire (Fear Q) [29]

Fig. 1 Flowchart of study sample

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were used to measure baseline severity of anxiety arousal and avoidance behaviour symptoms, respectively. The BAI and the Fear Q are both widely used and have proven to be highly valid and reliable [30, 31]. The Cronbach’s α in this study for the BAI and the Fear Q were .94 and .89, respectively.

Disability To measure disability at baseline, after two and after 4 years, we used the total score of the World Health Organization Disability Assessment Schedule II.(WHO- DAS-II) [32]. The WHODAS-II provides a functioning profile for six activity domains (cognition, mobility, self- care, social interaction, life activities and participation). To measure general disability, domain scores were com- bined into a total score. The WHODAS-II shows good inter-item reliability with a Cronbach’s α of .96 for the total score. In Hendriks et al. [11] a cross sectional study was conducted to compare the different disability domains of the WHODAS-II between different anxiety disorders and healthy controls. The results showed that disability was generally highest in multiple anxiety disorder (e.g. mean disability in cognition = 33.7) and social anxiety dis- order (mean = 32.7), followed by generalized anxiety disorder (mean = 27.2) and panic disorder with agorapho- bia (mean = 26.3), and lowest in panic disorder without agoraphobia (mean = 22.1). This pattern was consistently present across different disability domains, therefore for this study we choose to use only the total score of the WHODAS-II.

Covariates As done before, [11] covariates at baseline were set: age, gender, years of education attained, partner status, num- ber of somatic illnesses and comorbid depressive dis- order. Previous studies showed that these covariates are associated with both anxiety and disability [33, 34].

Statistical analyses SPSS Version 20.0 (SPSS Inc, Chicago, Illinois) was used for the statistical analyses. We used chi-square statistics for categorical and analyses of variance for continuous vari- ables to compare sociodemographic, clinical psychiatric characteristics and long-term disability between healthy controls and participants with anxiety disorders. Linear mixed models (LMM) [35] were used to analyse the rela- tionship between 1) baseline psychiatric status, 2) course trajectories and 3) symptom dimensions with the outcome long-term disability.

Results Table 1 presents the demographic and clinical characteris- tics of the total sample. A chronic course was most preva- lent in the multiple AD group (35.1 %). After 4 years

64.9 % of the participants with SAD, 68.6 % of PDA, 65.6 % of PD, 79.7 % of GAD and 51.1 % of multiple AD were without an anxiety disorder (X2 = 355.5, df = 25, p < .001). Anxiety arousal and avoidance behaviour symptoms were highest in the multiple AD group compared to other groups (BAI F = 286.2, df = 5, p < .001; Fear Q F = 205.12, df = 5, p < .001). Figure 2 shows 4-year disability patterns between partici-

pants with SAD, PDA, PD, GAD, multiple AD and healthy controls (n = 1235) at each time point. Healthy controls ex- perienced less disability compared to participants with any anxiety disorder and this differed significantly at baseline (all p-values < .001), 2-year follow-up (all p-values < .05) and 4-year follow-up (all p-values < .04). Generally, SAD and multiple AD participants experienced most disability. Dis- ability was lowest in PDA and PD, and GAD had an inter- mediate position. At baseline, participants with SAD, GAD and multiple AD experienced more disability than partici- pants with PDA and PD (all p-values < .03). Participants with multiple AD had more disability than participants with PD at 2 years (T1) (p = .01). At 4 years (T2), participants with SAD showed more disability than participants with PDA (p = .02), and participants with multiple AD showed more disability than participants with PD (p = .01) and PDA (p = .02). Table 2 shows LMM analyses for long-term disability.

Univariable analyses indicate that having an anxiety dis- order at baseline predicts long-term disability. SAD x time, PDA x time, GAD x time and multiple AD x time showed significant negative associations. This indicates that during follow-up the impact of the disorders on long-term disabil- ity became smaller. Course trajectories (remission, re- currence and chronic course) and symptom dimensions (anxiety arousal and avoidance behaviour) were also as- sociated with long-term disability. No associations were found for symptom dimensions x time, suggesting that associations did not significantly change over time. In Model 1 the degree was examined to which course

trajectories contribute to long-term disability across anxiety disorders. Baseline psychiatric status and chronic course remained significant predictors. Also SAD x time, PDA x time, GAD x time and multiple AD x time remained sig- nificant. This indicates that during follow-up the impact of baseline SAD, PDA, GAD and multiple AD on long-term disability became smaller. In Model 2 baseline psychiatric status and symptom

dimensions were assessed together. The results show that all coefficients decreased notably and only SAD, GAD, multiple AD, anxiety arousal and avoidance behaviour remained significant. PDA and PD did not remain sig- nificant. This indicates that anxiety arousal and avoid- ance behaviour lead to more long-term disability in anxiety disorders, which especially explain the found disability levels in PD and PDA.

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Fig. 2 Disability (total score WHODAS-II) over 4 years of time for baseline psychiatric status (n = 1235) *

Table 1 Demographic and clinical characteristics of the total sample (healthy controls and participants with different anxiety disorders, n = 1602)

Healthy controls SAD PDA PD GAD Multiple AD pa

n = 647 n = 191 n = 90 n = 84 n = 110 n = 480

Sociodemographics

Age (mean, SD) 41.1 (14.6) 37.3 (11.9) 40.1 (12.5) 38.3 (11.1) 37.4 (12.0) 40.8 (11.7) .001

Sex (% female) 61.7 64.9 74.4 59.5 69.1 68.5 .05

Education (mean, SD) 12.8 (3.2) 12.6 (3.2) 12.1 (3.4) 12.4 (3.1) 12.4 (3.1) 11.3 (3.3) <.001

Partner status (% yes) 75.0 56.5 70.0 73.8 70.0 63.8 <.001

Clinical psychiatric characteristics

Number of somatic illnesses (mean, SD) 0.7 (1.0) 0.8 (0.9) 0.9 (1.0) 0.7 (0.8) 0.7 (0.9) 1.1 (1.2) <.001

Comorbid depressive disorder (%) 0 41.9 38.7 40.5 62.7 72.5 <.001

Psychiatric course trajectories (%) <.001

Remission - 72.3 87.1 81.2 91.1 51.1

Recurrence - 10.8 4.3 14.1 7.6 13.8

Chronic course - 16.9 8.6 4.7 1.3 35.1

Psychiatric status after 4 years (%) <.001

No anxiety disorder - 64.9 68.6 65.6 79.7 51.1

Social anxiety disorder - 20.9 2.9 3.1 7.6 16.8

Panic disorder with agoraphobia - 0 8.6 4.7 0 6.3

Panic disorder without agoraphobia - 2.0 8.6 12.5 3.8 6.3

Generalized anxiety disorder - 4.1 5.7 1.6 8.9 7.2

Multiple anxiety disorder - 8.1 5.7 12.5 0 12.3

Symptom dimensions

Anxiety arousal (BAI, mean, SD) 4.1 (4.9) 13.9 (9.1) 19.1 (11.6) 14.2 (8.9) 14.6 (8.2) 23.1 (11.1) <.001

Avoidance behaviour (Fear Q, mean, SD) 12.1 (12.2) 34.4 (18.8) 32.1 (19.0) 22.8 (18.1) 25.0 (16.3) 43.7 (20.6) <.001 ap-value based on chi-square statistics for categorical variables and analyses of variances for continuous variables

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In Model 3, baseline psychiatric status, course trajector- ies and symptom dimensions were assessed together. SAD, GAD, multiple AD, anxiety arousal and avoidance behaviour remained significant but course trajectories not. Furthermore, SAD x time and GAD x time remained sig- nificant. This indicates that the impact of SAD and GAD on long-term disability remained irrespective of course and symptom dimensions.

Discussion The results showed that all anxiety disorders were associ- ated with more disability over 4 years of time compared to healthy controls, though differences became smaller over time. Long-term disability was most prevalent in participants

with SAD and multiple AD, and lowest in PDA and PD. GAD had an intermediate position. Furthermore, we found differences between course trajectories; a chronic course predicts long-term disability better than remission and re- currence. However, symptom dimensions seem to be

stronger predictors of long-term disability than course trajectories. Our finding that long-term disability is more prevalent in

SAD and multiple AD compared to other anxiety disor- ders, is in line with previous results [36, 37] Because SAD and multiple AD are more associated with a chronic course than other anxiety disorders [20, 22, 23] and a chronic course is associated with more disability, [21] we expected that long-term disability is more prevalent in SAD and multiple AD. Our results showed that a chronic course is indeed associated with long-term disability. Avoidance be- haviour was also associated with long-term disability in our study. We hypothesised that long-term disability would be high in SAD, PDA and multiple AD because of the high levels of avoidance behaviour in these disorder. However, PDA had a low position. So the assumption that avoidance behaviour predicts long-term disability better than anxiety arousal seems to be debatable. Our findings showed intermediate associations for

long-term disability and GAD. The association between GAD and disability may be particularly strong because

Table 2 Linear mixed model analyses for long-term disability (total score WHODAS-II)a

Disability

Univariable Model 1 Model 2 Model 3

ß (SE) p ß (SE) p ß (SE) p ß (SE) p

Baseline psychiatric status

Healthy controls Ref Ref Ref Ref

SAD 15.28 (1.55) <.001 14.26 (1.74) <.001 5.09 (1.42) <.001 4.38 (1.55) <.001

SAD x time -6.48 (0.61) <.001 -6.40 (0.61) <.001 -2.52 (0.57) .01 -2.56 (0.57) .01

PDA 9.31 (2.09) <.001 9.54 (2.24) <.001 -0.46 (1.88) .65 -0.65 (1.98) .52

PDA x time -4.18 (0.85) <.001 -4.04 (0.85) <.001 -0.07 (0.77) .94 -0.11 (0.77) .92

PD 5.96 (2.15) <.001 6.40 (2.29) <.001 0.46 (1.84) .65 0.23 (1.94) .82

PD x time -1.43 (0.88) .15 -1.29 (0.88) .20 -0.07 (0.77) .95 -0.11 (0.77) .92

GAD 13.01 (1.93) <.001 13.19 (2.07) <.001 6.62 (1.68) <.001 6.07 (1.77) <.001

GAD x time -5.80 (0.79) <.001 -5.58 (0.80) <.001 -3.52 (0.70) <.001 -3.55 (0.70) <.001

Multiple AD 20.93 (1.57) <.001 18.21 (1.58) <.001 3.58 (1.46) <.001 3.00 (1.58) .003

Multiple AD x time -7.61 (0.54) <.001 -7.54 (0.54) <.001 -1.31 (0.58) .19 -1.36 (0.58) .18

Psychiatric course trajectory

Healthy controls Ref Ref Ref

Remission 10.30 (0.82) <.001 -3.12 (1.12) .002 0.63 (0.84) .53

Recurrence 7.82 (1.66) <.001 -0.01 (1.70) .99 0.42 (1.23) .67

Chronic course 14.65 (1.32) <.001 3.65 (1.48) <.001 0.94 (1.08) .35

Symptom dimensions

Anxiety arousal 24.28 (0.04) <.001 12.49 (0.06) <.001 12.51 (0.06) <.001

Anxiety arousal x time 1.49 (0.02) .14 0.90 (0.03) .37 0.86 (0.03) .39

Avoidance behaviour 23.28 (0.02) <.001 10.58 (0.03) <.001 10.57 (0.03) <.001

Avoidance behaviour x time -1.40 (0.01) .16 0.17 (0.01) .87 0.14 (0.01) .89 aAnalyses corrected for covariates age, sex, education, partner status, number of somatic illnesses and comorbid depression Model 1: baseline psychiatric status and course trajectories; Model 2: baseline psychiatric status and symptom dimensions; Model 3: final model

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worry is pervasive and can be focused on any area (more general concerns, including social situations and physical concerns), whereas the focus of distress for SAD, PDA and PD is more narrow. Nevertheless, this finding is only partly in line with previous results. Naragon-Gainey et al. [12] found that GAD at baseline was more associ- ated with severe disability in certain areas (i.e. work, household, family, private leisure) compared to SAD and PDA/PD. However, after 2 years participants with GAD at baseline experienced no more disability than partici- pants with SAD and PDA/PD. Previous research showed that comorbidity between GAD and other mental disor- ders is high (e.g. major depressive disorder) [5, 38–41]. Possibly, this high comorbidity can explain the inconsist- ent results among previous research. However, other re- search pointed out that the disability seen in GAD cannot be explained by comorbidity [42]. The results showed that long-term disability is lowest

in PDA and PD which is partly in line with other studies [12, 13]. As mentioned in our previous study [11], dis- ability in PDA and PD is generally associated with phys- ical disability [14, 37]. Unfortunately, physical disability is not measured by the WHODAS-II very well and we can therefore not establish whether PDA and PD partici- pants in this study have more physical disability com- pared to other participants. Baseline psychiatric status and symptom dimensions

were stronger predictors for long-term disability than course trajectories. This indicates that participants with SAD, GAD and multiple AD remain more disabled than PDA and PD, despite the course. Furthermore, although remission rates were relatively high, participants with anxiety disorders at baseline remain more disabled than healthy controls after 4 years. Possibly, baseline psychi- atric status contains important information which was not measured in our study, such as age of onset, envir- onmental factors, personality characteristics, and pre- morbid functioning. Another possibility is that when participants remit over 4 years, subthreshold anxiety symptoms may still be present and cause disability. Pre- vious research indeed showed that subthreshold anxiety is also associated with long-term disability [43, 44]. This study has several strengths. Adequate analyses were

performed because of the structured psychiatric interview, the large representative sample, and the longitudinal de- sign. LMM analyses made it possible that all available in- formation was used, even from participants with partly missing data. This study has also limitations. First, not all anxiety disorders are included in NESDA (e.g., obsessive compulsive disorder, posttraumatic stress disorder and spe- cific phobia). However, in this study DSM-IV diagnoses were used instead of DSM-5. In DSM-5 obsessive compul- sive disorder and posttraumatic stress disorder do not be- long to the anxiety disorders chapter anymore and are

discussed in separate chapters. Next, participants with de- pressive disorders were not excluded but analyses were corrected for comorbid depression. Furthermore, there can be differences in disability in the duration of a chronic dis- order. For example, having a chronic anxiety disorder for 20 years causes possibly a different level of disability than having a chronic anxiety disorder for 5 years.

Conclusions Generally, long-term disability was highest in participants with SAD and multiple AD, followed by participants with GAD, and lowest in participants with PDA and PD. This means that various anxiety disorders have different disabil- ity levels over 4 years of time, so diagnostic distinction is important for treatment focus. When there is more than one anxiety disorder present there must be examined which anxiety symptoms are the most severe and disabling for the patient so treatment can focus on these symptoms. Our re- sults show that anxiety arousal and avoidance behaviour lead to more long-term disability in anxiety disorders com- pared to course trajectories. Taken together, symptom di- mensions in anxiety disorders give important information about disability over time. The use of symptom dimensions could eventually give more insight in all the complex asso- ciations in psychopathology and determine how psychiatric problems develop over time. The efficacy of transdiagnostic interventions for anxiety disorder patients (e.g. acceptance and commitment therapy and cognitive behavioural ther- apy) which are targeting these underlying processes might be evaluated or new interventions can be developed in order to prevent long-term disability. The results of our studies support the concepts of the DSM-5, which includes dimensional aspects of diagnosis along with categories.

Acknowledgements The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (zon-Mw, grant number 10-000-1002) and is supported by participating universities and mental health care organisations (VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Scientific Institute for Quality of Healthcare (IQ healthcare), Netherlands Institute for Health Services Research (NIVEL) and Netherlands Institute of Mental Health and Addiction (Trimbos Institute)).

Availability of data and materials The data of NESDA will not be made available in order to protect the participant’s identity.

Authors’ contributions AB and BP designed the Netherlands Study of Depression and Anxiety and wrote the protocol. SH designed the analysis plan, managed the literature searches and analyses, and wrote the manuscript. CL contributed to the statistical analyses. SH, JS, CL, FH, RG, NB, BP and AB had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. SH, JS, CL, FH, RG, NB, BP and AB critically revised the manuscript. SH, JS, CL, FH, RG, NB, BP and AB read and approved the final manuscript.

Hendriks et al. BMC Psychiatry (2016) 16:248 Page 6 of 8

Competing interests On behalf of all authors, the corresponding author states that there are no competing interests.

Consent for publication Non applicable.

Ethics approval and consent to participate The research protocol was approved centrally by the ethical review board of VU University Medical Center. Subsequently it was approved by the local ethical review boards of Leiden University Medical Center and University Medical Center Groningen. The study was performed in accordance with the ethical standards of the Declaration of Helsinki. All participants provided written informed consent.

Author details 1Department of Psychiatry, Pro Persona Mental Health Care, Zandstraat 54, Veenendaal 3905 ED, The Netherlands. 2Pro Persona Mental Health Care, Radboud University Nijmegen, Reinier Postlaan 6, Nijmegen 6525 GC, The Netherlands. 3Department of Psychiatry/EMGO Institute, VU University Medical Center, AJ Ernststraat 887, Amsterdam 1081 HL, The Netherlands. 4Pro Persona Mental Health Care, Willy Brandtlaan 20, Ede 6717 RR, The Netherlands. 5Netherlands Institute of Mental Health and Addiction, Da Costakade 45, Utrecht 3521 VS, The Netherlands.

Received: 2 September 2015 Accepted: 24 June 2016

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