Prevalence, incidence, and comorbidity of clinically diagnosed obsessive–compulsive disorder in Taiwan: A national population-based study

Prevalence, incidence, and comorbidity of clinically diagnosed obsessive–compulsive disorder in Taiwan: A national population-based study

Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎ Contents lists available at ScienceDirect Psychiatry Research journal homepage: www.elsevier.com/locate/psychre...

321KB Sizes 1 Downloads 23 Views

Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎

Contents lists available at ScienceDirect

Psychiatry Research journal homepage: www.elsevier.com/locate/psychres

Prevalence, incidence, and comorbidity of clinically diagnosed obsessive–compulsive disorder in Taiwan: A national population-based study Li-Chung Huang a,b,g, Kuen-Jer Tsai a, Hao-Kuang Wang a,c, Pi-Shan Sung a,d, Ming-Hsiu Wu a,e, Kuo-Wei Hung a,f, Sheng-Hsiang Lin a,n a

Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan Department of Psychiatry, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan Department of Neurosurgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan d Department of Neurology, National Cheng Kung University Hospital, Tainan, Taiwan e Department of Neurology, Chi Mei Medical Center, Liouying, Tainan, Taiwan f Department of Neurology, Yuan's General Hospital, Kaohsiung, Taiwan g Chia Nan University of Pharmacy and Science, Tainan, Taiwan b c

art ic l e i nf o

a b s t r a c t

Article history: Received 19 July 2013 Received in revised form 6 August 2014 Accepted 9 August 2014

Obsessive–compulsive disorder (OCD) is a chronic debilitating anxiety disorder significant in intrusive thoughts and compensation repetitive behaviors. Few studies have reported on this condition Asia. This study estimated the prevalence, incidence and psychiatric comorbidities of OCD in Taiwan. We identified study subjects for 2000–2008 with a principal diagnosis of OCD according to the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) diagnostic criteria by using National Health Research Institute database. These patients received either outpatient or inpatient care for their condition. Rates were directly age- and sex-adjusted to the 2004 Taiwan population distribution. The estimated mean annual incidence was 27.57 per 105 inhabitants and the one year prevalence was 65.05 per 105 inhabitants. Incidence and prevalence increased with age, peaking at age 18–24 years in males and at 35–44 years in females. About 53% of adults ( Z 18 years) and 48% of child and adolescent patients (6–17 years) had one or more comorbid psychiatric conditions. The most common comorbid diagnosis was depressive disorders for both adult and child-adolescent patients. We found a lower prevalence and incidence of clinically diagnosed OCD than that of community studies. Many Asian patients with OCD also had various psychiatric comorbidities, a clinically relevant finding. & 2014 Elsevier Ireland Ltd. All rights reserved.

Keywords: Obsessive and compulsive disorder Incidence Prevalence Comorbidity National Health Insurance Taiwan

1. Introduction Obsessive–compulsive disorder (OCD) was a chronic debilitating anxiety disorder significant in intrusive thoughts accompanied by compensatory repetitive behaviors (APA, 2000). In the other opinion, OCD was not classified as an anxiety disorder in th latest diagnostic criteria (APA, 2013). The 10th most restrictive illness in terms of decreased quality of life, lowered occupational function and loss of income according to the World Health Organization, OCD also causes disarranged development, social withdrawal and interpersonal relationship problems (Calvocoressi et al., 1995; Leon et al., 1995; Murray and Lopez, 1996; Freeman et al., 2003). OCD symptoms and signs have been investigated from a cross-cultural n Correspondence to: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, 138, Shengli Road, Tainan, Taiwan. Tel.: þ 886 6 2353535x5962; fax: þ 886 6 2758781. E-mail address: [email protected] (S.-H. Lin).

perspective and its treatment in all age groups is likely undervalued (Torres et al., 2006). Untreated OCD may result in difficulties with academic performance and higher rates of unemployment in all fields (Calvocoressi et al., 1995; Leon et al., 1995). The many management choices include medication includes antidepressant agents (SSRIs specify) and low dose of antipsychotics agent, cognitive-behavior therapy and even electroconvulsant therapy in some refractory patients. OCD patients with higher obsessive and compulsive symptoms are at greater risk of higher levels of anxiety, depressive symptoms and suicidal attempts (Nestadt et al., 1998). Previous epidemiological studies have postulated the prevalence of OCD in community or primary care populations. In these, the 1-year prevalence varied between 0.1% and 3% and life time prevalence varied between 0.3% and 4% (Heyman et al., 2001; Ford et al., 2003; Somers et al., 2006; Fireman et al., 2001; Grenier et al., 2009; Canals et al., 2012; Himle et al., 2008; Veldhuis et al., 2012; Subramaniam et al., 2012; Fineberg et al., 2013). Studies in the

http://dx.doi.org/10.1016/j.psychres.2014.08.011 0165-1781/& 2014 Elsevier Ireland Ltd. All rights reserved.

Please cite this article as: Huang, L.-C., et al., Prevalence, incidence, and comorbidity of clinically diagnosed obsessive–compulsive disorder in Taiwan: A national population-based study. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.08.011i

2

L.-C. Huang et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎

primary care population showed lower prevalence (Fireman et al., 2001; Veldhuis et al., 2012) than most of those done in community populations. Although many prevalence studies mentioned above (Heyman et al., 2001; Ford et al., 2003; Somers et al., 2006; Fireman et al., 2001; Grenier et al., 2009; Canals et al., 2012; Himle et al., 2008; Veldhuis et al., 2012; Subramaniam et al., 2012; Fineberg et al., 2013) have described the distribution of OCD, few incidence studies have characterized its demographic features. Of the five studies investigating the incidence of OCD (Valleni-Basile et al., 1996; Nestadt et al., 1998; De Graaf et al., 2002; Veldhuis et al., 2012; Fineberg et al., 2013), the results vary from 0.016% in a German clinical study of diagnosed OCD to 5.1% in a England community study. Most studies used age-limited community samples, some had small sample size (Oakley-Browne et al., 1989; Wittchen et al., 1992) and one was based on a linked clinical database (Veldhuis et al., 2012), Furthermore, some studies were based on patients from special institutions (Valleni-Basile et al., 1996; Heyman et al., 2001; Ford et al., 2003) or on urban populations (Chen et al., 1993; Henderson et al., 2001; Mohammadi et al., 2004). These differences in study design also reflect inconsistencies between studies in the method of diagnosis, i.e., whether it was based on semi-structured interviews or clinical diagnosis. All these epidemiological studies differed by country, and most were based on a community sample, not the primary care population. A well-designed study of clinically diagnosed and treated OCD will provide updated data for academic, clinical and public health use in decision-making. Some studies of OCD include demographic variables such as age, gender and socioeconomic status. The age at onset of OCD is important in the clinical, neurobiological, and bio-genetic development of the illness. While most investigations determined the average age of onset of OCD to be during late adolescence and early adulthood (Noshirvani et al., 1991; Attiullah et al., 2000), a pattern of gender differences has appeared; male patients have been consistently noted to have an earlier onset than females. one study that have calculated the Axis I or Axis II comorbidity of OCD (Bogetto et al., 1999; Matsunaga et al., 2000) found a higher rate of social phobia, hypomanic episodes, depersonalization disorder and substance-related disorders in males, and impulse control disorders and EDs in females. Another study (Matsunaga et al., 2000) found that schizotypal personality disorder was more frequently diagnosed in males, and borderline personality disorder tended to be more prevalent in females. In addition, studies in the adolescent population suggest that older adolescents may be at higher risk of developing OCD than younger ones (Thomsen, 1993). Other studies have found an association between earlier onset and comorbidity with somatoform, tic and impulse-control disorders, greater family history of obsessive–compulsive symptoms, more symptom severity and higher treatment resistance (Bolton et al., 2007; de Mathis et al., 2008, 2009; Janowitz et al., 2009). In several clinical and community studies (Karno et al., 1988; Rasmussen and Eisen, 1992a; Klein Hofmeijer-Sevink et al., 2013), adult OCD patients had high rates of comorbid psychiatric conditions such as depressive disorders, anxiety spectrum disorders and bipolar disorder. Similarly, high comorbidity rates were observed in a series of studies of consecutively-referred children and adolescents with OCD (Leckman et al., 1994; Geller et al., 1996; Reddy et al., 2000; Jaisoorya et al., 2003), particularly attention deficit disorder, Tourette's disorder, oppositional defiant disorder and overanxious disorder. Furthermore, OCD is not only highly associated with major depressive disorder (MDD), anxiety disorders, child psychiatric disorder and other mental disorders (Fireman et al., 2001), but also with eating disorders (ED), especially anorexia nervosa in females (Swinbourne and Touyz, 2007; Micali et al., 2011). The Clarifying the psychiatric comorbidity patterns of OCD will allow researchers to

examine the constellations of common traits, which may elucidate common etiological factors (Grados et al., 2003). This wild range of prevalence of OCD and comorbidity psychiatric disorders is likely due to the differences between studies in study populations, culture and research design. In recent years, few comprehensive epidemiological studies have been conducted on patients with OCD in Asia. The aims of the current study were to determine the prevalence and incidence of OCD in Taiwan and to investigate the possible association of comorbid psychiatric disorders with OCD by using the claim data of the National Health Insurance (NHI).

2. Methods 2.1. Data source The NHI claims database, including records for ambulatory care, hospital inpatient care, and prescription medication, was provided by the National Health Research Institute (NHRI). The NHI database covered 99% of the population of Taiwan (23 million) from 1995 until the present and the NHRI provides a database of 1,000,000 random subjects for research purposes. The Longitudinal Health Insurance Database 2000 (LHID2000) contains all the original claims data of 1,000,000 beneficiaries, randomly sampled from the year 2000 Registry for Beneficiaries of the NHI claim database. We used the LHID2000 with antecedent data from 1st January 1996, which allowed us to exclude those diagnosed with OCD before 31st December 1999. The study protocol was approved by the Chia-Yi Christian General Hospital Research Ethics Committee.

2.2. Study sample We used a registry-based prospective cohort design to estimate the incidence, prevalence and psychiatric comorbidity of OCD in the general population in Taiwan. Diagnostic coding of the NHI database is done according to the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) diagnostic criteria. The database also provides scrambled patient identification number, patient birth date, gender, scrambled physician identification number and physician specialty. All the psychiatric disorders in this study were diagnosed by well-trained clinical psychiatrists or physicians. Study subjects with a primary diagnosis of OCD (ICD-9-CM: 300.3) who then received either outpatient or inpatient care were identified to determine prevalence and incidence. We analyzed the subjects by age, breaking them into seven groups (6–10, 11–17, 18–24, 25–34, 35–44, 45–64 and 65 years and up). To calculate the incidence and prevalence rate of diagnosed OCD, we used the LHID2000 database from 1 January 2000 until 31 December 2008. To consider the relationship of OCD to other psychiatric disorders, comorbid psychiatric disorders were recorded only if they occurred from at least one year before to one year after the incidence date of OCD diagnosis during the 10 year period. To determine the comorbidities associated with OCD, we divided the subjects into two groups by age (418 and r18 years). The comorbid psychiatric disorders recorded for adult OCD subjects were MDD (ICD-9-CM: 296.2 and 296.3), bipolar disorder (ICD-9CM: 296.0, 296.1, 296.4, 296.5, 296.6, 296.7 and 296.8), schizophrenia (ICD-9-CM: 295), posttraumatic stress disorder (PTSD, ICD-9-CM: 309.81), anxiety disorders (ICD-9-CM: 300.00, 313.0), panic disorder (ICD-9-CM: 300.01), social phobia (ICD-9-CM: 300.23), generalized anxiety disorder (GAD, ICD-9-CM: 300.02), EDs (ICD-9-CM: 307.50, 307.51, 307.1) and adjustment disorder (ICD-9-CM: 300.9). For adolescent and child subjects, we also recorded the following psychiatric comorbid conditions: attention deficit disorder (ICD-9-CM: 314.00, 314.01, 314.9), Tourette's disorder (ICD-9-CM: 307.23), conduct disorder (ICD-9-CM: 312, 312.3, 312.9) and autistic spectrum disorder (ICD-9-CM: 299). For the non-adult subjects, GAD, panic disorder, PTSD, anxiety disorder, nonspecified and over anxious disorder were grouped as anxiety disorders.

2.3. Statistical analysis We calculated sex-age-specific and adjusted incidence and prevalence of treated OCD as the number of incident and prevalent cases per 100,000 inhabitants. The age distribution was directly adjusted to that of the population of Taiwan in 2004. The comorbidity of diagnosed OCD was computed as the number of incident cases in which occurred per 1000 case person-years by sex and age group. We also calculated the male/female ratio for patients with diagnosed OCD and the comorbid psychiatry disorders of both groups. The 95% confidence intervals (CI) of incidence rate, prevalence rate and male–female ratios were estimated using the Poisson distribution. SAS version 9.2 (SAS, Inc., Cary, NC) was used to analyze the data. For this study, the significance level was set at 0.05.

Please cite this article as: Huang, L.-C., et al., Prevalence, incidence, and comorbidity of clinically diagnosed obsessive–compulsive disorder in Taiwan: A national population-based study. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.08.011i

L.-C. Huang et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎

3. Results 3.1. Incidence and prevalence Table 1 details the incidence and Table 2 the prevalence of agespecific and sex-adjusted rates (per 100,000 inhabitants) of treated OCD in Taiwan for the study period. A total of 2040 incidence cases and 4810 prevalence cases were found for 2000–2008. The estimated mean annual incidence was 27.6 per 105 inhabitants (0.0276%) and the one-year prevalence was 65.1 per 105 inhabitants (0.0651%). The mean age at diagnosis for treated OCD patients was 37.65 years (standard deviation [S.D.] 16.22 years) for women and 33.46 years (S.D. 17.47 years) for men, a statistically significant difference (Po0.001). The incidence increased with age in adolescent and early adult patients of both sexes, peaking at the age of 18–24 years in males, 35–44 years in females and 18–24 years in both. The incidence of treated OCD was stable over time, ranging from 0.0225% to 0.0327% over the follow-up period. For incidence, the subject groups younger than 25 years all had higher male/female ratios. Prevalence was similar to incidence, peaking at the age of 18–24 years in males, 35–44 years in females and 18– 24 years in both. In one-year prevalence, the male/female ratio was higher in all age groups younger than 35 years. For those above age 65, the prevalence of clinically-recognized OCD markedly decreased in both genders. Prevalence rates increased over time in both males and females.

3.2. Psychiatric comorbidity In all, 43.8% of adult OCD patients had one comorbid psychiatric condition and 9.4% had two or more recorded in the NHI database during the study period (Table 3, upper panel). For nonadults, 35.7% had one and 12.6% had two or more psychiatric

3

comorbidities (Table 3, lower panel). There was no significant gender difference in the number of comorbidities. Table 4 shows the distribution of OCD comorbidities by gender in adults. The most commonly-diagnosed comorbid conditions were depressive disorders (24.7%), general anxiety disorder (8.2%), MDD (8.3%) and other anxiety disorders (7.7%). For the two major psychiatric disorders, 7.7% of OCD patients had a diagnosis of schizophrenia and 3.2% had bipolar disorder. The comorbidity M/F ratio of schizophrenia was 1.5 (95% CI: 1.0–2.0) and social phobia was 4.7 (95% CI: 1.1–22.2). Table 5 shows the most commonly diagnosed comorbid conditions for child-adolescent OCD patients: depressive disorders (15.5%), attention deficit disorder (12.9%) and anxiety disorders (11.2%). The total rate of comorbidity of schizophrenia was 4.3%. Together, the debilitating comorbidities of Tourette's disorder (4.0%) and autistic disorder (5.4%) were diagnosed in nearly one in ten pre-adult subjects. While most comorbid psychiatric disorders showed no obvious gender difference, anxiety disorders (2.3, 95% CI: 1.0–5.5) were more common in male patients.

4. Discussion To our knowledge, the present study is the first prospectively followed-up cohort study using NHI data to estimate the prevalence, incidence and associated psychiatric comorbidities in treated OCD patients in Taiwan. Our study is not only the first to investigate the prevalence of OCD after the 1985 Taiwan Psychiatric Epidemiological Project (Hwu et al., 1989), but also the most recent investigation of the gender differences in comorbid Axis I psychiatric disorders among OCD patients in Asia. Our results confirm the high number of psychiatric comorbidities among adult, adolescent and child patients with OCD. The findings also

Table 1 Age-specific and sex-adjusted incidence rate (per 100,000 inhabitants) of diagnosed obsessive–compulsive disorder patients in Taiwan, 2000–2008. Age, years

Total No.

6–10 11–17 18–24 25–34 35–44 45–64 464 Total

67 210 353 435 382 446 147 2040

Male

Female

Rate (95% CI)

No.

Rate (95% CI)

No.

10.8 21.3 40.2 35.3 31.0 26.6 19.3

(8.2–13.3) (18.4–24.2) (36.0–44.4) (32.0–38.7) (27.9–34.1) (24.1–29.1) (16.1–22.4)

44 133 199 211 152 176 71

13.6 26.2 46.2 36.0 25.8 22.0 18.5

(9.6–17.6) (21.7–30.6) (39.8–52.6) (31.2–40.9) (21.7–29.9) (18.8–25.3) (14.2–22.8)

23 77 154 224 230 270 76

27.6 (26.7–28.4)

986

27.2 (25.5–28.9)

1054

M/F Ratio (95% CI) Rate (95% CI) 7.7 16.1 34.4 34.7 35.7 30.8 20.0

(4.6–10.9) (12.5–19.7) (29.0–39.9) (30.2–39.3) (31.1–40.3) (27.1–34.4) (15.5–24.5)

27.9 (26.2–29.6)

1.8 1.6 1.3 1.0 0.7 0.7 0.9

(1.1–2.9) (1.2–2.2) (1.1–1.7) (0.9–1.3) (0.6–0.9) (0.6–0.9) (0.7–1.3)

1.0 (0.9–1.1)

CI, confidence interval. M/F, male–female ratio.

Table 2 Age-specific and sex-adjusted prevalence rate (per 100,000 inhabitants) of diagnosed obsessive–compulsive disorder patients in Taiwan, 2000–2008. Age, years

Total

Male

No.

Rate (95% CI)

6–10 11–17 18–24 25–34 35–44 45–64 464

95 384 835 1128 1039 1015 304

15.2 39.0 95.1 91.7 84.2 60.5 41.1

Total

4810

65.1 (63.8–66.4)

(12.2–18.3) (35.1–42.9) (88.6–101.5) (86.3–97.0) (79.1–89.3) (56.8–64.3) (36.6–45.7)

No. 59 250 530 622 467 442 159 2529

Female Rate (95% CI) 18.2 49.2 123.0 106.2 79.2 55.3 41.4

(13.6–22.8) (43.1–55.3) (122.5–133.4) (97.9–114.6) (72.0–86.4) (50.2–60.5) (35.0–47.9)

69.9 (67.1–72.6)

No. 36 134 305 506 572 573 155 2281

M/F Ratio (95% CI) Rate (95% CI) 12.1 28.0 68.2 78.4 88.8 65.3 40.8

(8.1–16.0) (23.2–32.8) (60.5–75.8) (71.6–85.3) (81.5–96.1) (60.0–70.6) (34.4–47.3)

60.4 (57.9–62.9)

1.5 1.8 1.8 1.4 0.9 0.8 1.0

(1.0–2.3) (1.4–2.3) (1.6–2.1) (1.2–1.5) (0.8–1.0) (0.8–1.0) (0.8–1.3)

1.2 (1.1–1.2)

CI, confidence interval. M/F, male–female ratio.

Please cite this article as: Huang, L.-C., et al., Prevalence, incidence, and comorbidity of clinically diagnosed obsessive–compulsive disorder in Taiwan: A national population-based study. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.08.011i

L.-C. Huang et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎

4

Table 3 The number of comorbid psychiatric disorders in adult (18 years and older) and child and adolescent (6–17 years) patients with obsessive–compulsive disorder. Number of comorbidities

Total

Male

n Adult 0 1 2þ Child and adolescent 0 1 2þ

% (95% CI)

1763 822 775 166 277 143 99 35

n

46.6 (44.3–49.0) 44.0 (41.5–46.1) 9.4 (8.1–10.0) 51.6 (45.7–57.5) 35.7 (30.1–41.4) 12.6 (8.7–16.5)

809 397 337 75 177 86 64 27

Female % (95% CI)

n

49.1 (45.6–52.5) 41.7 (38.3–45.1) 9.3 (7.3–11.3) 48.6 (41.2–56.0) 36.2 (29.1–43.2) 15.3 (10.0–20.6)

% (95% CI)

954 425 438 91 100 57 35 8

44.5 (41.4–47.7) 45.6 (42.4–48.8) 9.5 (7.7–11.4) 57.0 (47.3–66.7) 35.0 (25.7–44.3) 8.0 (2.7–13.3)

CI, confidence interval.

Table 4 Comorbid psychiatric disorders among adult (18 years and older) patients with obsessive–compulsive disorder. Comorbid diagnosis

Major depressive disorder Bipolar disorder Depressive disorders Anxiety disorders Panic disorder Generalized anxiety disorder Posttraumatic stress disorder Social phobia Eating disorder Schizophrenia Adjustment disorder

Total (N ¼ 1,763)

Male (N ¼809)

Female (N ¼ 954)

%

95% CI

%

95% CI

%

95% CI

8.3 3.2 24.7 7.7 0.2 8.2 0.3 0.6 0.6 7.7 2.2

7.0–9.6 2.4–4.0 22.7–26.7 6.5–9.0 0–0.4 6.9–9.5 0–0.5 0.2–0.9 0.3–1.0 6.5–9.0 1.5–2.9

7.0 2.7 24.0 8.4 0 7.3 0.2 1.0 0 9.3 2.2

5.3–8.8 1.6–3.8 21.0–26.9 6.5–10.3 0 5.5–9.1 0–0.6 0.3–1.7 0 7.3–11.3 1.2–3.2

9.4 3.6 25.3 7.1 0.3 9.0 0.3 0.2 1.2 6.4 2.2

7.6–11.3 2.4–4.7 22.5–28.0 5.5–8.8 0–0.7 7.2–10.8 0–0.7 0–0.5 0.5–1.8 4.8–7.9 1.3–3.1

M/F ratio

95% CI

0.7 0.8 0.9 1.2 0 0.8 0.8 4.7 0 1.5 1.0

0.5–1.1 0.5–1.3 0.8–1.1 0.9–1.6 0 0.6–1.1 0.1–4.7 1.0–22.2 0 1.0–2.0 0.5–1.8

CI, confidence interval. M/F, male–female ratio.

indicate the neglect and under-estimation of OCD in this population. So far, few studies have examined the incidence rate of OCD. The incidence rate in our study (0.028%) was lower than that of two community studies (0.2% and 0.055%) (Nestadt et al., 1998; De Graaf et al., 2002) and a little higher than the recent primary care study (0.016%) (Veldhuis et al., 2012). The higher incidence in community studies, which do not use rigorous clinical diagnosis to identify OCD, may considerably over-estimate the presence of the disorder. The one-year prevalence (0.065%) of our study was also lower than those of several community studies (0.3–4%) (Somers et al., 2006; Subramaniam et al., 2012) but similar to that of a study of clinically-recognized OCD (0.084%) (Fireman et al., 2001) and slightly lower than that of a diagnosed OCD study (0.14%) (Veldhuis et al., 2012). An explanation for the different incidence and prevalence rates of OCD in these studies may be sought in the different methodologies they used. The results of the current study are likely to under-estimates of the community rates. For example, the study subjects in our study were the OCD patients who sought for treatment which may reflect ascertainment bias. Otherwise, some community studies may over-estimate incidence and prevalence because some of them had a lack of rigor in their definitions of OCD and their failure to include severity assessments. However, some studies used validated assessments like Structure Clinical Interview Diagnosis (SCID) (Fireman et al., 2001; Ford et al., 2003; Fineberg et al., 2013), ICD-10 (Heyman et al., 2001; Himle et al., 2008) or Composite International Diagnostic Interview (CIDI) (Subramaniam et al., 2012; Chong et al., 2012) to estimate prevalence or incidence. Another reason for the lower prevalence rate in our studies may be some studies only included adults, which may reflect the higher rates. In addition, most

incidence and prevalence rates of previous studies were collected only in the urban or capital of the countries and the higher rates may reflect the greater knowledge about the symptoms of OCD in large cities with a well-developed public health infrastructure. Our results for clinically diagnosed and treated OCD suggest that only a minority of OCD cases are clinically recognized and receive appropriate treatment. As with other studies using different instruments in community and clinical samples, there exists a big gap between the estimated community prevalence of OCD and the proportions found in help-seeking populations in our study. Two recent studies found the percentage of lifetime of OCD patients who had sought treatment was 10.2% in Singapore (Subramaniam et al., 2012; Chong et al., 2012). In other developed countries, one (Torres et al., 2007) indicated 9.4% of patients with lifetime OCD had seen a psychiatrist and 4.6% had seen a psychologist in the United Kingdom; and another American study (Ruscio et al., 2010) found that 29.2% of lifetime OCD sample had received treatment at some point in their life. The communitybased studies of these developed countries mentioned above indicated lifetime treatment-seeking rates ranging from 9.4% to 29.2%.Thus, the adjusted prevalence of OCD patients in our study is ranging from 0.23% to 0.7% (i.e. 0.065  100/29.2 and 0.065  100/ 9.4). The adjusted estimates are similar to the estimates of 0.3% to 4% in other studies. Our results present the first time the medical interventions used to treat OCD. The NHIR database did not list the age of onset of OCD symptoms, so this study reports the age at first diagnosis and treatment. Some patients were screened by questionnaire studies before symptom onset because of a presence of family history or other mood symptoms before diagnosis of OCD. Some patients may have had a delay in diagnosis or treatment because

Please cite this article as: Huang, L.-C., et al., Prevalence, incidence, and comorbidity of clinically diagnosed obsessive–compulsive disorder in Taiwan: A national population-based study. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.08.011i

L.-C. Huang et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎

5

Table 5 Comorbid psychiatric disorders among child and adolescent (6–17 years) patients with obsessive–compulsive disorder. Comorbid diagnosis

Major depression Bipolar disorder Depressive disorders Anxiety disorders Eating disorder Attention deficit disorder Tourette disorder Conduct disorder Adjustment disorder Autistic disorder Schizophrenia

Total (N ¼277)

Male (N ¼177)

Female (N¼ 100)

%

95% CI

%

95% CI

%

95% CI

4.0 0.3 15.5 11.2 0 12.9 4.0 1.8 4.7 5.4 4.3

1.7–6.3 0.3–1.1 11.2–19.8 7.4–14.9 0 9.0–17.0 1.7–6.3 0.2–3.4 2.2–7.2 2.7–8.1 1.9–6.7

4.0 0.6 13.0 14.1 0 14.5 6.2 1.1 6.8 6.2 4.0

1.0–6.8 0.5–1.7 8.0–17.9 9.0–19.3 0 9.5–19.8 2.7–9.8 0.4–2.7 3.1–10.5 2.7–9.8 1.0–6.8

4.0 0 20 6.0 0 10.0 0 3.0 1.0 4.0 5.0

0.2–7.8 0 12.2–27.8 1.3–10.7 0 4.1–15.9 0 0.3–6.3 1.0–3.0 0.2–7.8 0.7–9.3

M/F ratio

95% CI

0.9 0 0.6 2.3 0 1.5 0 0.4 6.8 1.6 0.8

0.2–3.3 0 0.4–1.1 1.0–5.5 0 0.7–2.9 0 0.1–2.2 0.9–51.4 0.5–4.8 0.3–2.4

CI, confidence interval. M/F, male–female ratio.

of the challenge of diagnosing OCD. On the whole, our findings suggest a significant gender difference in the mean age of treatment for OCD. Studies of childhood rates of OCD have found that 1.5 to 2.5 times as many boys as girls suffer from the disorder (Eichstedt and Arnold, 2001). In adults, studies have generally found an equal distribution in males and females (Rasmussen and Eisen, 1992a). Our results indicated male/female ratios for child and adolescent (1.65) and adult (1.0) OCD patients similar to those reported in the literature. Our findings that the male/female ratio of incidence of OCD was slightly higher in the 11–24 age group and slightly lower in the 35–64 age group in Taiwan also corresponds to previous findings (Noshirvani et al., 1991; Thomsen, 1993; Attiullah et al., 2000). In terms of gender, men had significantly higher prevalence and incidence rates of OCD. This result should raise some alarm, since adult women in general exhibit a greater propensity to seek out professional help and psychiatric treatment (Kessler et al., 1981). The results also corresponded to the literature that male subjects have an earlier age of onset than female subjects (Zohar, 1999). However, the gender difference in our study is limited in the age distribution of detected cases. To further clarify our results, we analyzed a fixed cohort over the 10 year period to determine the psychiatric comorbidities and gender differences in those with OCD. Psychiatric comorbidity is common in adults and juveniles with OCD. According to many studies, more than 50% of OCD subjects also have another psychiatric disorders (Rasmussen and Eisen, 1992b; Bogetto et al., 1999, Klein Hofmeijer-Sevink et al., 2013). Our data shows that more than 53.4% of adults and 48.4% of adolescent and child subjects have a current comorbidity with other Axis I disorders. The high comorbidity rates may be due to the nature of OCD as a neurodegenerative disorder, as well as the organization of diagnostic systems, which encourages multiple diagnoses. However, patients with pure OCD are less likely to seek for treatment than those with comorbidity disorders. The comorbidities are likely to be the major presenting problems for the patients and the OCD would be detected in the subsequent evaluation period. The comorbidity rate might be over-estimated in current study. While we were unable to calculate the association of substance-related disorders and other personality traits with OCD, it is of note that more than 50% of OCD patients in Taiwan also need treatment for some another psychiatric disorder. The prevalence of comorbid psychiatric conditions in adult OCD patients is consistent with the high rates of comorbid disorders reported in epidemiological (Karno et al., 1988) and clinical studies (Fireman et al., 2001). The results replicated the previously reported strong associations between OCD and bipolar disorder, depressive disorders and anxiety disorders (Perugi et al., 1997;

Milos et al., 2002; Nestadt et al., 2003). As with clinical studies that have documented frequent comorbidity between OCD and bipolar disorders, we found the same tendency. In our study, other anxiety disorder and GAD were the most common comorbidities among the anxiety spectrum disorders. However, in another study, panic disorder was more common (Fireman et al., 2001). Few studies to date have explored the relationship of social phobia and OCD, a relationship which calls for further evaluation. Of special interest is our finding of an association between ED and OCD. While the association we found did not achieve statistical significance, we believe the association warrants more study, and a longer follow up could clarify the association, as in a previous study (Milos et al., 2002). The present study is also the first to examine psychiatric comorbidities in terms of the male/ female ratio instead of case-control odds ratio in Asia. We found a high male/female ratio not only in social phobia, but also in schizophrenia and adjustment disorders, associations noted elsewhere (Bogetto et al., 1999; Matsunaga et al., 2000). These high rates of comorbidity imply that OCD adult patients should be carefully assessed for comorbid conditions and that their treatment in clinical practice may be more complicated than that done in clinical trials, which employ numerous exclusion criteria. The child and adolescent patients in our study had strikingly high rates of depressive disorders, anxiety disorders and attention deficit disorder; they also had high rates of MDD, autistic spectrum disorders, schizophrenia and Tourette's disorder. Our results generally correspond to those of previous juvenile comorbidity studies (Leckman et al., 1994; Geller et al., 1996). Despite commonalities, we found a higher rate of attention deficit disorders in these nonadult patients, as well as anxiety disorders in male patients and Tourette's disorder in female patients. Child and adolescent OCD has been considered different from adult-onset OCD, with some considering it a developmental subtype of the disorder with a high rate of attention deficit disorders and tic disorders (Jaisoorya et al., 2003). The issue will require a larger study sample and longer observation period to settle. For now, clinicians should take into consideration the gender and comorbid psychiatric disorders of adolescents and children with OCD when devising their medical and psychotherapy treatment. Strength of this study is that using insurance claim datasets in clinical research which is easy access to the longitudinal records for a large sample of patients from different geographic areas. The second strength of the study was our use of the NHI claim data, which presents less selection and recall bias than other methods and has a very small likelihood of loss to follow-up of cohort members. Third, we used a strict definition to select study cases, as all had to have a DSM-IV-TR and ICD-9 diagnosis by a clinical

Please cite this article as: Huang, L.-C., et al., Prevalence, incidence, and comorbidity of clinically diagnosed obsessive–compulsive disorder in Taiwan: A national population-based study. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.08.011i

L.-C. Huang et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎

6

psychiatrist or physician who were well treated. Fourth, ours is the first to observe gender differences by calculating the male/female ratio for treated OCD patients with axis I comorbidity in Asia. Using claims data presents some limitations to our study. First, because a diagnosis of OCD was based on data from the secondary database, it could be argued that a determination of OCD based on the ICD coding would be less accurate than that based on a conventional psychiatric interview. Second, variables such as socioeconomic status and income were not available in the current study. We also were not able to estimate the severity of OCD, the subgroups of obsessive thoughts and compulsive behaviors, subjects with subthreshold OCD or the personality comorbidities associated with OCD; such information would likely provide more information about the illness. In addition, other psychiatric symptoms (e.g., depressive) or psychiatric disorders could interfere with and mask OCD symptoms. Finally, psychiatrists may misdiagnose OCD because of the patient's other severe medical conditions or a physician may diagnose OCD, but not in time to provide adequate treatment. Actually, our data revealed rates of treatment for OCD, while a community survey detects the true rates of the disorder. In conclusion, the 1-year prevalence of clinically-treated OCD within this prospective cohort study was approximately 0.065%. While previous epidemiological studies may have found many subthreshold or misclassified cases of OCD who did not need treatment, all those suffering from OCD should receive the benefits of appropriate medical treatment. In many cases, they will require treatment for other psychiatric comorbidities as well as OCD. To further clarify our findings, prospective studies with structured assessments of OCD symptoms, severity and comorbidity are highly recommended.

Declaration of conflict of interest None.

Acknowledgments This study was supported by Ditmanson Medical Foundation Chia-Yi Christian Hospital Research Program (R101-17). This study is based on data from the National Health Insurance (NHI) Research Database provided by the Bureau of NHI, Department of Health, and managed by the National Health Research Institutes, Taiwan (Registered number NHIRD-101–549).

References APA, 2000. Diagnostic and Statistical Manual of Mental Disorders, Fourth edition American Psychiatric Press, Washington, DC (Text Revision (DSM-IV-TR)). APA, 2013. Diagnostic and Statistical Manual of Mental Disorders, Fifth edition American Psychiatric Press, Washington, DC (DSM-V). Attiullah, N., Eisen, J.L., Rasmussen, S.A., 2000. Clinical features of obsessive– compulsive disorder. The Psychiatric Clinics of North America 23, 469–491. Bogetto, F., Venturello, S., Albert, U., Maina, G., Ravizza, L., 1999. Gender-related clinical differences in obsessive–compulsive disorder. European Psychiatry 14, 434. Bolton, D., Rijsdijk, F.U.H., O’Connor, T.G., Perrin, S., Eley, T.C., 2007. Obsessive– compulsive disorder, tics and anxiety in 6-year-old twins. Psychiatry and Clinical Neurosciences 37, 39–48. Calvocoressi, L., Lewis, B., Harris, M., Trufan, S.J., Goodman, W.K., McDougle, C.J., Price, L.H., 1995. Family accommodation in obsessive–compulsive disorder. The American Journal of Psychiatry 152, 441–443. Canals, J, Hernández-Martínez, C, Cosi, S, Voltas, N, 2012. The epidemiology of obsessive–compulsive disorder in Spanish school children. Journal of anxiety disorders 26, 746–752. Chen, C.N., Wong, J., Lee, N., Chan-Ho, M.W., Lau, J.T.F., Fung, M., 1993. The Shatin community mental health survey in Hong Kong: II. Major findings. Archives of General Psychiatry 50, 125.

Chong, S., Abdin, E., Sherbourne, C., Vaingankar, J., Heng, D., Yap, M., Subramaniam, M., 2012. Treatment gap in common mental disorders: the Singapore perspective. Epidemiology and Psychiatric Sciences 21, 195–202. De Graaf, R., Bijl, R., Ravelli, A., Smit, F., Vollebergh, W., 2002. Predictors of first incidence of DSM‐III‐R psychiatric disorders in the general population: findings from the Netherlands Mental Health Survey and Incidence Study. Acta Psychiatrica Scandinavica 106, 303–313. de Mathis, M.A., Diniz, J.B., Shavitt, R.G., Torres, A.R., Ferrao, Y.A., Fossaluza, V., Pereira, C., Miguel, E., do Rosario, M.C., 2009. Early onset obsessive–compulsive disorder with and without tics. CNS Spectrums 14, 362–370. de Mathis, M.A., do Rosario, M.C., Diniz, J.B., Torres, A.R., Shavitt, R.G., Ferrao, Y.A., Fossaluza, V., de Braganca Pereira, C.A., Miguel, E.C., 2008. Obsessive–compulsive disorder: influence of age at onset on comorbidity patterns. European Psychiatry 23, 187–194. Eichstedt, J.A., Arnold, S.L., 2001. Childhood-onset obsessive–compulsive disorder: a tic-related subtype of OCD? Clinical Psychology Review 21, 137. Fineberg, N.A., Hengartner, M.P., Bergbaum, C.E., Gale, T.M., 2013. A prospective population-based cohort study of the prevalence, incidence and impact of obsessive–compulsive symptomatology. International Journal of Psychiatry in Clinical Practice 17, 170–178. Fireman, B., Koran, L.M., Leventhal, J.L., Jacobson, A., 2001. The prevalence of clinically recognized obsessive–compulsive disorder in a large health maintenance organization. The American Journal of Psychiatry 158, 1904–1910. Ford, T., Goodman, R., Meltzer, H., 2003. The British Child and Adolescent Mental Health Survey 1999: the prevalence of DSM-IV disorders. Journal of the American Academy of Child & Adolescent Psychiatry 42, 1203–1211. Freeman, J.B., Garcia, A.M., Fucci, C., Karitani, M., Miller, L., Leonard, H.L., 2003. Family-based treatment of early-onset obsessive–compulsive disorder. J Child Adolescent Psychopharmacology 13 (Suppl 1), S71–S80. Geller, D.A., Biederman, J., Griffin, S., Jones, J., Lefkowitz, T.R., 1996. Comorbidity of juvenile obsessive–compulsive disorder with disruptive behavior disorders. Journal of the American Academy of Child and Adolescent Psychiatry 35, 1637–1646. Grados, M.A., Walkup, J., Walford, S., 2003. Genetics of obsessive–compulsive disorders: new findings and challenges. Brain & Development 25 (Suppl 1), S55–S61. Grenier, S, Préville, M, Boyer, R, O'Connor, K, 2009. Prevalence and correlates of obsessive–compulsive disorder among older adults living in the community. Journal of Anxiety Disorders 23, 858–865. Henderson, S., Andrews, G., Hall, W., 2001. Australia's mental health: an overview of the general population survey. Australian and New Zealand Journal of Psychiatry 34, 197–205. Heyman, I., Fombonne, E., Simmons, H., Ford, T., Meltzer, H., Goodman, R., 2001. Prevalence of obsessive–compulsive disorder in the British nationwide survey of child mental health. The British Journal of Psychiatry 179, 324–329. Himle, JA, Muroff, JR, Taylor, RJ, et al., 2008. Obsessive–compulsive disorder among African Americans and blacks of Caribbean descent: results from the national survey of American life. Depression and Anxiety 25, 993–1005. Hwu, H.G., Yeh, E.K., Chang, L.Y., 1989. Prevalence of psychiatric disorders in Taiwan defined by the Chinese Diagnostic Interview Schedule. Acta Psychiatrica Scandinavica 79, 136–147. Jaisoorya, T., Janardhan Reddy, Y., Srinath, S., 2003. Is juvenile obsessive–compulsive disorder a developmental subtype of the disorder? European Child & Adolescent Psychiatry 12, 290–297. Janowitz, D., Grabe, H.J., Ruhrmann, S., Ettelt, S., Buhtz, F., Hochrein, A., SchulzeRauschenbach, S., Meyer, K., Kraft, S., Ferber, C., Pukrop, R., Freyberger, H.J., Klosterkotter, J., Falkai, P., John, U., Maier, W., Wagner, M., 2009. Early onset of obsessive–compulsive disorder and associated comorbidity. Depression and Anxiety 26, 1012–1017. Karno, M., Golding, J.M., Sorenson, S.B., Burnam, M.A., 1988. The epidemiology of obsessive–compulsive disorder in five US communities. Archives of General Psychiatry 45, 1094–1099. Kessler, R.C., Brown, R.L., Broman, C.L., 1981. Sex differences in psychiatric helpseeking: evidence from four large-scale surveys. Journal of Health and Social Behavior, 49–64. Klein Hofmeijer-Sevink, M., van Oppen, P., van Megen, H.J., Batelaan, N.M., Cath, D.C., van der Wee, N.J, 2013. Clinical relevance of comorbidity in obsessive compulsive disorder: the Netherlands OCD Association study. Journal of Affective Disorders 150, 847–854. Leckman, J.F., Grice, D.E., Barr, L.C., de Vries, A.L., Martin, C., Cohen, D.J., McDougle, C.J., Goodman, W.K., Rasmussen, S.A., 1994. Tic-related vs. non-tic-related obsessive compulsive disorder. Anxiety 1, 208–215. Leon, A.C., Portera, L., Weissman, M.M., 1995. The social costs of anxiety disorders. The British Journal of Psychiatry 166, 19–22. Matsunaga, H., Kiriike, N., Matsui, T., Miyata, A., Iwasaki, Y., Fujimoto, K., Kasai, S., Kojima, M., 2000. Gender differences in social and interpersonal features and personality disorders among Japanese patients with obsessive–compulsive disorder. Comprehensive Psychiatry 41, 266–272. Micali, N., Hilton, K., Natatani, E., Heyman, I., Turner, C., Mataix-Cols, D., 2011. Is childhood OCD a risk factor for eating disorders later in life? A longitudinal study. Psychiatry and Clinical Neurosciences, 1–7. Milos, G., Spindler, A., Ruggiero, G., Klaghofer, R., Schnyder, U., 2002. Comorbidity of obsessive–compulsive disorders and duration of eating disorders. International Journal of Eating Disorders 31, 284–289. Mohammadi, M.R., Ghanizadeh, A., Rahgozar, M., Noorbala, A.A., Davidian, H., Afzali, H.M., Naghavi, H.R., Yazdi, S.A.B., Saberi, S.M., Mesgarpour, B., 2004. Prevalence of obsessive–compulsive disorder in Iran. BMC Psychiatry 4, 2.

Please cite this article as: Huang, L.-C., et al., Prevalence, incidence, and comorbidity of clinically diagnosed obsessive–compulsive disorder in Taiwan: A national population-based study. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.08.011i

L.-C. Huang et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎ Murray, C.J.L., Lopez, A.D., 1996. A comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. The Global Burden of Disease and Injury Series, Vol. 1. Nestadt, G., Addington, A., Samuels, J., Liang, K.Y., Bienvenu, O.J., Riddle, M., Grados, M., Hoehn-Saric, R., Cullen, B., 2003. The identification of OCD-related subgroups based on comorbidity. Biological Psychiatry 53, 914–920. Nestadt, G., Bienvenu, O.J., Cai, G., Samuels, J., Eaton, W.W., 1998. Incidence of obsessive–compulsive disorder in adults. The Journal of Nervous and Mental Disease 186, 401–406. Noshirvani, H.F., Kasvikis, Y., Marks, I.M., Tsakiris, F., Monteiro, W., 1991. Genderdivergent aetiological factors in obsessive–compulsive disorder. The British Journal of Psychiatry 158, 260–263. Oakley-Browne, M.A., Joyce, P.R., Wells, J.E., Bushnell, J.A., Hornblow, A.R., 1989. Christchurch Psychiatric Epidemiology Study, Part II: six month and other period prevalences of specific psychiatric disorders. Australian and New Zealand Journal of Psychiatry 23, 327–340. Perugi, G., Akiskal, H.S., Pfanner, C., Presta, S., Gemignani, A., Milanfranchi, A., Lensi, P., Ravagli, S., Cassano, G.B., 1997. The clinical impact of bipolar and unipolar affective comorbidity on obsessive–compulsive disorder. Journal of Affective Disorders 46, 15–23. Rasmussen, S.A., Eisen, J.L., 1992a. The epidemiology and clinical features of obsessive compulsive disorder. The Psychiatric Clinics of North America 15, 743–758. Rasmussen, S.A., Eisen, J.L., 1992b. The epidemiology and differential diagnosis of obsessive compulsive disorder. Journal of Clinical Psychiatry 53 (4 suppl), S4–S10. Reddy, Y., Reddy, P.S., Srinath, S., Khanna, S., Sheshadri, S., Girimaji, S., 2000. Comorbidity in juvenile obsessive–compulsive disorder: a report from India. Canadian Jjournal of Psychiatry 45, 274. Ruscio, A., Stein, D., Chiu, W., Kessler, R., 2010. The epidemiology of obsessive– compulsive disorder in the National Comorbidity Survey Replication. Molecular psychiatry 15, 53–63. Somers, J.M., Goldner, E.M., Waraich, P., Hsu, L., 2006. Prevalence and incidence studies of anxiety disorders: a systematic review of the literature. Canadian Journal of Psychiatry 51, 100–113.

7

Subramaniam, M., Abdin, E., Vaingankar, J.A., Chong, S.A., 2012. Obsessive–compulsive disorder: prevalence, correlates, help-seeking and quality of life in a multiracial Asian population. Social Psychiatry and Psychiatric Epidemiology 47, 2035–2043. Swinbourne, J.M., Touyz, S.W., 2007. The co-morbidity of eating disorders and anxiety disorders: a review. European Eating Disorders Review 15, 253–274. Thomsen, P.H., 1993. Obsessive–compulsive disorder in children and adolescents. Self-reported obsessive–compulsive behaviour in pupils in Denmark. Acta Psychiatrica Scandinavica 88, 212–217. Torres, A., Prince, M.J., Bebbington, P.E., Bhugra, D.K., Brugha, T.S., Farrell, M, 2007. Treatment seeking by individuals with obsessive–compulsive disorder from the British Psychiatric Morbidity Survey of 2000. Psychiatric Services 58, 977–982. Torres, A., Prince, M., Bebbington, P., Bhugra, D., Brugha, T., Farrell, M., Jenkins, R., Lewis, G., Meltzer, H., Singleton, N., 2006. Obsessive–compulsive disorder: prevalence, comorbidity, impact, and help-seeking in the British National Psychiatric Morbidity Survey of 2000. The American Journal of Psychiatry 163, 1978–1985. Valleni-Basile, L.A., Garrison, C.Z., Waller, J.L., Addy, C.L., McKeown, R.E., Jackson, K.L., Cuffe, S.P., 1996. Incidence of obsessive–compulsive disorder in a community sample of young adolescents. Journal of the American Academy of Child and Adolescent Psychiatry 35, 898–906. Veldhuis, J., Dieleman, J.P., Wohlfarth, T., Storosum, J.G., van Den Brink, W., Sturkenboom, M.C.J.M., Denys, D., 2012. Incidence and prevalence of “diagnosed OCD” in a primary care, treatment seeking, population. International Journal of Psychiatry in Clinical Practice 16, 85–92. Wittchen, H.-U., Essau, C.A., Zerssen, D., Krieg, J.-C., Zaudig, M., 1992. Lifetime and six-month prevalence of mental disorders in the Munich Follow-Up Study. European Archives of Psychiatry and Clinical Neuroscience 241, 247–258. Zohar, A.H., 1999. The epidemiology of obsessive–compulsive disorder in children and adolescents. Child and Adolescent Psychiatric Clinics of North America 8, 445–460.

Please cite this article as: Huang, L.-C., et al., Prevalence, incidence, and comorbidity of clinically diagnosed obsessive–compulsive disorder in Taiwan: A national population-based study. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.08.011i