RESEARCH REPORT

doi:10.1111/j.1360-0443.2011.03559.x

Co-occurrence of obsessive-compulsive disorder and substance use disorder in the general population
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Rianne M. Blom1, Maarten Koeter1, Wim van den Brink1, Ron de Graaf3, Margreet ten Have3 & Damiaan Denys1,2
Department of Psychiatry, Academical Medical Centre, University of Amsterdam, Amsterdam, the Netherlands,1 the Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands2 and Netherlands Institute of Mental Health and Addiction, Utrecht, the Netherlands3

ABSTRACT Aim Very little is known about the relationship between obsessivecompulsive disorder (OCD) and substance use disorder (SUD). The aim of this study is to compare the co-occurrence of OCD with SUD to the co-occurrence of SUD with other psychiatric disorders in a representative community sample. Design In order to examine the association of SUD and OCD, logistic regression analyses were used generating odds ratios and 95% condence intervals for lifetime prevalence and 12-month prevalence. Setting and participants Cross-sectional data were derived from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), a large representative sample of the Dutch population (n = 7076). Measurements The Composite International Diagnostic Interview (CIDI) 1.1 was used to assess Diagnostic and Statistical Manual of Mental Disorders Axis I criteria for psychiatric disorders. Findings The life-time and 12-month odds of being diagnosed with SUD in subjects with OCD are signicantly higher than the odds of SUD for people without a psychiatric disorder. In men, the co-occurrence of substance dependence and OCD is signicantly higher than the co-occurrence of substance dependence and other psychiatric disorders, whereas in women this co-occurrence does not differ signicantly. Conclusions The co-occurrence of substance dependence in obsessivecompulsive disorder is higher than the co-occurrence of substance dependence in other non-obsessive compulsive disorder DSM disorders, especially in men. Keywords Compulsivity, epidemiology, obsessionality, obsessive-compulsive disorder, reward-model, substance abuse, substance dependence, substance use disorder.
Correspondence to: Damiaan Denys, Department of Psychiatry, Academic Medical Center, University of Amsterdam, PA.2-179, PO Box 75867, 1070 AW Amsterdam, the Netherlands. E-mail: ddenys@gmail.com Submitted 1 February 2011; initial review completed 25 March 2011; nal version accepted 21 June 2011

INTRODUCTION Obsessivecompulsive disorder (OCD) is characterized by the presence of obsessions, compulsions or most commonly both. Obsessions are egodystonic, recurrent and persistent thoughts, impulses or images that are experienced as intrusive and may cause anxiety. Compulsions are repetitive behaviours or mental acts that the subject feels compelled or forced to do in response to an obsession or according to rigid rules [1]. In DSM-III-R and DSM-IV, substance use disorders (SUDs) are characterized by a maladaptive pattern of substance use, leading to clinically signicant impairment or distress [1]. In ICD-10, craving is an additional symptom, indicating the (obsessive) urge, strong desire or sense of compulsion to take
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the drug [2]. Craving is also a proposed new criterion for a substance use disorder in DSM-V [3]. OCD and SUD have an overlapping phenomenology. Although obsessions and compulsions are not present in SUD, one can easily recognize obsessionality and compulsivity in addiction resembling OCD. Patients with addiction are obsessed with their drugs and feel compelled to take them. In general, OCD patients obsess about something they fear or perceive as unpleasant, while subjects with SUD obsess about something that is experienced as pleasant (e.g. rush). It should be noted, however, that in both disorders ambivalence about these thoughts may be present at the same time [4]. Obsessive thinking in OCD is largely egodystonic, whereas in SUD it is generally egosystonic. Nevertheless, in both
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disorders, obsessionality and compulsivity causes distress. The OCD patient diminishes anxiety and stress by repeated compulsive behaviours or mental acts, the SUD patient by obtaining money and using drugs. More recently the later stages of SUD have been conceptualized as compulsive drug-seeking (e.g. [5,6]). In SUD patients these compulsive behaviours (drug-taking) are often related to the obsession (craving) and can either provide direct pleasure (reward craving leading to drug use as positive reinforcement) or serve the resolution of a negative mood state (relief craving leading to drug use as negative reinforcement) [7]. In OCD patients, compulsions generally represent an attempt to relieve anxiety (negative reinforcement), although it cannot be excluded that they also experience some pleasure (positive reinforcement) from their habitual actions that unfortunately end in compulsive behaviour. One of the most frequently quoted brain models of addiction shows the development over time from cognitions and behaviours based mainly on positive reinforcement processes into cognitions and behaviours motivated mainly by negative reinforcement [8,9]. Addiction starts with positive reinforcement, characterized by reward deciency (anhedonia) and a search for positive reward in combination with impulsivity, and then tends to move to negative reinforcement that is derived from a further decrease in brain reward circuit activity in combination with an increase in compulsivity [10]. The transition from impulsivity to compulsivity has been conrmed in experimental animal research, in which high impulsivity in rats predicted the transition from controlled to compulsive drug-taking [5]. This compulsive end stage of addition may resemble the compulsivity in OCD. Moreover, in full-blown addiction, loss of function occurs in the frontal cortex systems that control executive function, contributing to poor decision-making and gain of function in the brain stress systems [9,10]. Similar decits are seen in obsessivecompulsive disorder [11,12]. There is extensive literature showing high levels of psychiatric comorbidity in people with SUD, both in the general population and in treatment-seeking populations [1316] and especially in anxiety disorder populations [1719]. However, much less is known about the specic association between SUD and OCD. Prevalence rates vary due to differences in sampling methods. In general population studies in the United States and Great Britain the percentage of OCD cases with comorbid SUD is 17.626.5% for drug abuse/dependence [2022], 24.138.6% for alcohol abuse/dependence [2023] and 38.6% for substance use in general [21]. SUD life-time prevalence rates among individuals receiving treatment for OCD range from 9.8% to 26.9% [2428]. Even less is known about the association of OCD and SUD compared to the association between other
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psychiatric disorders and SUD. As the onset of OCD generally precedes the onset of SUD [14], the aim of the present study is to investigate the co-occurrence of OCD with SUD compared to the co-occurrence of SUD with other internalizing psychiatric disorders that are assumed to generally follow the onset of SUD (e.g. depression [29]). Because gender differences are common in substance use disorder, analyses will be stratied by gender [30,31]. As drugs may be used as self-medication for psychiatric disorders [32,33], we hypothesize that the likelihood of the co-occurrence is higher in subjects with OCD than in subjects without any psychiatric disorder. Secondly, based on the presented similarities in phenomenology and neurobiology, we hypothesize that SUDs in general (abuse and dependence) are associated with OCD, but that this association is more pronounced in substance dependence (SD), as pre-clinical and clinical research [5,6] has demonstrated that the end stage of substance use disorder (dependence) results in compulsivity which resembles OCD. We are aware that some of the misuse criteria seem to represent a more severe level of substance abuse (SA) than some of the dependence criteria, and we also know that not all patients with substance abuse will ultimately develop substance dependence, but there are clear indications that SD represents a more serious and generally later stage of substance use problems than SA [9,34].

METHODS Sample selection Data are derived from the Netherlands Mental Health Survey and Incidence Study (NEMESIS). NEMESIS is a nationally prospective study, with repeated measurements in 1996, 1997 and 1999 from a national, multistage random sample of municipalities and households (age 1864 years) in the Netherlands. The analyses presented here are based on data from the rst measurement in 1996. A total of 7076 people were interviewed and the response rate was 69.7%. The respondents reected the Dutch population adequately with regard to civil status, sex and urbanicity. For more detailed information on the objectives and design of NEMESIS, see further [35]. Psychiatric disorders The World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) 1.1 was used to assess Diagnostic and Statistical Manual of Mental Disorders (DSM) Axis I criteria for all psychiatric disorders. The CIDI is a fully structured interview based on the Present State Examination and the Diagnostic Interview Schedule. The CIDI has good testre-test reliability [36] and validity [37] for all psychiatric disorders that were examined in NEMESIS. The CIDI was developed by the World
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Table 1 Total numbers of substance use disorder (SUD), substance abuse, substance dependence and obsessivecompulsive disorder (OCD), stratied by gender (non-weighted data). Men (3299) Life-time Any SUD Substance abuse Substance dependence OCD 925 (28.0%) 651 (19.7%) 316 (9.6%) 29 (0.9%) 12-month 415 (12.6%) 227 (6.9%) 200 (6.1%) 24 (0.7%) Women (3777) Life-time 272 (7.2%) 165 (4.4%) 117 (3.1%) 32 (0.9%) 12-month 118 (3.1%) 59 (1.6%) 62 (1.6%) 16 (0.4%)

Health Organization and is being used world-wide in epidemiological studies [38]. All interviewers underwent a 4-day training course at the WHO-CIDI training centre of the Academic Medical Centre in Amsterdam. NEMESIS participants were classied into three mutually exclusive subgroups: no DSM-III-R disorder; DSMIII-R disorder but no DSM-III-R OCD; and DSM-III-R OCD. The classication was based on 12-month prevalence and life-time prevalence data. Participants were included in the non-DSM group if they did not full the DSM-III-R criteria of any psychiatric disorder, except possibly substance abuse or dependence (including alcohol, excluding nicotine). Subjects were included in the DSM non-OCD group if they fullled the DSM-III-R criteria of at least one psychiatric disorder and possibly substance abuse or dependence but did not full the DSM-III-R criteria for OCD, i.e. mood disorders (major depression, bipolar disorder and dysthymia), schizophrenia, eating disorders (anorexia nervosa and bulimia nervosa) and anxiety disorders (panic disorder, agoraphobia, social phobia, simple phobia, generalized anxiety disorder). Lastly, participants fullling the DSM-III-R criteria of OCD with or without co-occurring SUD were included in the OCD group. Other comorbid DSM-III-R diagnoses were allowed. SUD is dened as fullling the DSM-III-R criteria for SD or SA (including alcohol, excluding nicotine). Statistical analyses Predictive Analytic Software (PWAS) for Windows version 18.0 was used to conduct the analyses [SPSS Inc., Chicago, IL, USA, 2010]. In order to examine the association of SUD and OCD logistic regression analysis was used generating odds ratios (ORs) and 95% condence intervals (CIs). Analyses were stratied by gender. To prevent selection bias and improve generalizability of the results to the general Dutch population, weighted data were used in the analyses. Based on post-stratication, a weighting factor was constructed to correct for different response rates in the different strata which enabled us to generalize the results to the general population. The following
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Table 2 Distribution of any substance use disorder (SUD)over the three categories stratied by gender (non-weighted data). Men (3299) Life-time Non-DSM DSM non-OCD OCD 2559 711 29 12-month 2903 379 17 Women (3777) Life-time 2329 1416 32 12-month 2950 811 16

OCD: obsessivecompulsive disorder.

population characteristics from 1996 obtained from Statistics Netherlands were used to dene the following strata: sex, age, marital status (ve categories) and urbanization (ve categories) (see elsewhere [35]).

RESULTS Sample The non-weighted sample consisted of 7076 individuals with a mean age of 41.2 years (range 1864) and 53.4% (standard deviation 5.0) women. The total numbers of SUD, SA, SD and OCD in the population are displayed in Table 1. The actual observed number of respondents on which all analyses were based are displayed in Table 2 stratied by gender. Relation of OCD and SUD In Table 3 both life-time prevalence and 12-month prevalence of any SUD for the three diagnostic groups are presented stratied by gender. In all diagnostic groups both life-time prevalence and 12-month prevalence of SUD were substantially higher in men than in women. For both men and women life-time prevalence and 12-month prevalence for SUD seemed to be lowest in the non-DSM group. The prevalence was substantially higher in the group with any DSM-disorder (excluding OCD) and was highest in the OCD group. Table 3 suggested an increased risk for SUD among people suffering from OCD. This relation appeared to be stronger in women.
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Table 3 Prevalence [95% condence interval (CI)] of any substance use disorder (SUD), substance abuse and substance dependence stratied by gender (weighted data). Men (3590) Life-time prevalence % (95% CI) Any SUD Non-DSM DSM non-OCD OCD Substance abuse Non-DSM DSM non-OCD OCD Substance dependence Non-DSM DSM non-OCD OCD 12-month prevalence % (95% CI) Women (3501) Life-time prevalence % (95% CI) 12-month prevalence % (95% CI)

26.6 (25.028.2) 40.3 (36.843.9) 54.6 (37.471.8) 20.1 (18.521.7) 24.3 (21.227.4) 19.8 (12.826.8) 7.6 (6.68.6) 18.7 (16.021.4) 41.3 (24.258.4)

13.1 (11.914.3) 21.5 (17.625.4) 36.1 (13.658.6) 7.8 (6.88.8) 7.8 (5.310.3) 11.6 (0.026.7) 5.7 (4.96.5) 13.8 (10.517.1) 31.6 (9.853.4)

3.9 (3.14.7) 13.0 (11.214.7) 23.5 (7.839.2) 2.5 (1.93.1) 7.7 (6.39.1) 13.9 (1.226.6) 1.6 (1.02.2) 5.7 (4.37.1) 12.0 (0.024.0)

2.2 (1.62.8) 8.1 (6.110.1) 11.5 (0.028.9) 1.3 (0.91.7) 4.0 (2.65.4) 5.1 (0.017.1) 1.0 (0.61.4) 4.0 (2.65.4) 11.5 (0.028.9)

OCD: obsessivecompulsive disorder.

Table 4 Effect of obsessivecompulsive disorder (OCD) [odds ratio (OR) 95% condence interval (CI)] on the likelihood for substance use disorder (SUD); substance abuse and substance dependence (weighted data). Life-time Men Any substance use disorder OCD versus non-DSM OCD versus DSM non-OCD Women 12-month Men Women

3.32 (1.676.61) 7.52 (3.1118.18) 1.78 (0.893.58) 2.06 (0.864.93) P < 0.001 P < 0.001 Group gender interaction P < 0.001 0.98 (0.412.31) 6.28 (2.1318.55) 0.77 (0.321.83) 1.93 (0.665.62) P = 0.044 P < 0.001 Group gender interaction P < 0.001 8.51 (4.2017.23) 8.36 (2.6128.81) 3.06 (1.496.25) 2.25 (0.727.09) P < 0.001 P < 0.001 Group gender interaction P = 0.477

3.75 (1.449.75) 5.67 (1.0630.46) 2.06 (0.775.47) 1.48 (0.277.94) P < 0.001 P < 0.001 Group gender interaction P < 0.01 1.54 (0.576.46) 4.07 (0.3646.28) 1.56 (0.366.76) 1.28 (0.1114.71) P = 0.836 P < 0.001 Group gender interaction P < 0.001 7.55 (2.7920.38) 12.33 (2.2567.69) 2.87 (1.047.99) 3.08 (0.5616.95) P < 0.001 P < 0.001 Group gender interaction P = 0.377

Substance abuse OCD versus non-DSM OCD versus DSM non-OCD

Substance dependence OCD versus non-DSM OCD versus DSM non-OCD

Logistic regression analysis dependent variable any SUD, substance abuse and substance dependence, respectively, independent variables group (nonDSM, DSM non-OCD, OCD), gender and group gender interaction.

To formally test the relationship between OCD and SUD, logistic regression analyses were used (Table 4). Using life-time data for both genders, the odds of being diagnosed with SUD in subjects with OCD was substantially and signicantly higher then the odds for people without a psychiatric disorder (men OR 3.32, 95% CI 1.676.61; women OR 7.52, 95% CI 3.1118.18). Moreover, subjects with OCD also had higher odds of being diagnosed with SUD than people suffering from other non-OCD psychiatric disorders. However, these differ 2011 The Authors, Addiction 2011 Society for the Study of Addiction

ences were smaller and did not reach statistical signicance (men OR 1.78, 95% CI 0.893.58; women OR 2.06, 95% CI 0.864.93). The effect of OCD on SUD was stronger for women than for men (group gender interaction P < 0.001). Twelve-month data showed comparable associations between OCD and SUD. Due to the low prevalence of OCD in the general population the OCD group was relatively small, resulting in large standard errors and overlapping prevalence CIs for the DSM nonOCD and the OCD groups. However, considering the
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power issue, the data were suggestive for OCD to result in higher odds of a SUD diagnosis than in other psychiatric disorders.

Relation of OCD with SA and SD Next we assessed the relationship between OCD and SUDs separately for SD and SA (Table 4). The odds of being diagnosed with SA was signicantly higher for women with OCD than for women without a psychiatric diagnosis using life-time prevalence, whereas it was not in men (group gender interaction P < 0.001). The relation between SD and OCD showed a different picture (Table 4). In life-time as well as 12-month data the odds of being diagnosed with SD was signicantly higher for people with OCD than for people without a psychiatric diagnosis in men and women. For men, the difference in odds for SD between those with OCD and those with other psychiatric disorders reached statistical signicance: life-time prevalence (OR 3.06, 95% CI 1.496.25) and 12-month prevalence (OR 2.87, 95% CI 1.047.99), whereas this was not the case in women.

DISCUSSION To the best of our knowledge, this is the rst study examining the association between OCD and SUD, SA and SD in a carefully conducted representative general population study stratied by gender. Several conclusions can be drawn. First, the life-time and 12-month odds of being diagnosed with SUD in subjects with OCD are signicantly higher than the odds of SUD for people without a psychiatric disorder. Secondly, when considering the individual diagnoses, it is concluded that in men the co-occurrence of SD and OCD is signicantly higher than the co-occurrence of SD and other psychiatric disorders, in life-time as well as 12-month data, whereas this is not the case in women. The life-time presence of SUD is higher when being diagnosed with a life-time presence of any DSM disorder (excluding OCD) and the life-time presence of OCD. This is consistent with previous studies [13,15,23]. The absolute prevalences are difcult to compare with other studies, due to the use of different diagnostic categories and the failure of many studies to stratify by gender. The 54.6% life-time prevalence of any substance use disorder in men and the 23.5% in women among OCD are comparable with a recent general population study from the United States reporting life-time prevalence of any substance use disorder of 38.5% [21]. In two population studies, lifetime SD is estimated around 14% [21,23]. This is lower than the 41.3% of SD in men and higher than the 12.0% in women found in the present study. However,
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the current study stratied the sample by gender and included alcohol dependence, whereas the other studies did not. Overall, the absolute life-time and 12-month prevalences of SUD, SA and SD in all groups are higher in men than in women. These ndings are consistent with previous research [30,31]. Noticeably, the life-time co-occurrence of OCD and SA is only higher in women. A possible explanation might be that men show SA-like behaviours relatively frequently even if they have no (psychiatric) problems, whereas women generally do not show SA-like behaviours, but only when they have (serious) problems or when there is (serious) psychopathology. We could not conrm our hypothesis that life-time/ 12-month OCD/SUD co-occurrence is signicantly higher than other life-time/12-month co-occurrence of SUD with other DSM disorders. However, there was a trend in the expected direction and the lack of a signicant difference is likely to result from the low prevalence of OCD in the general population. A similar trend was recently found in a large community study in American adolescents examining the co-occurrence of SUD and anxiety disorders [19]. In this study, OCD was the anxiety disorder showing the most consistent association with SUD among girls. Another large population study found higher alcohol dependence, tobacco use and drug dependence in the OCD group compared to the group with other neuroses [23]. However, the difference was signicant only for alcohol dependence. In order to solve the power problem, additional studies are needed using enriched community samples or treatment-seeking populations. The nding that the odds of being diagnosed with SUD in subjects with OCD is signicantly higher than the odds for people without a psychiatric disorder (in life-time as well as 12-month data) agrees with data from the National Epidemiologic Survey on Alcohol Related Conditions (NESARC) study [18], in which positive associations with anxiety disorders and substance SUDs were found. The 12-month ORs of SUDs and anxiety disorders in the NESARC study vary between 1.6 and 3.1, which is lower than the ORs of SUDs and OCD that we found in our study. This conrms our hypothesis that, apart from being an anxiety disorder, OCD seems to have a special relationship with SUDs. As suggested in the Introduction, OCD and SUD are both compulsive disorders. Compulsivity is dened as the repetitive, irresistible urge to perform a behaviour and is probably due to a defect in the reward circuitry [9,10,39]. The current ndings seem to represent the fact that the compulsive end stage of addiction (dependence) might resemble phenomenologically the compulsive behaviour in OCD. Our study conrms that especially life-time and
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12-month SD (the end stage of excessively using drugs or alcohol) is related to OCD (signicantly in men, trend in women). This is consistent with the ndings of Torres et al., who found alcohol and drug dependence to have a stronger relation with OCD than with other anxiety disorders, whereas this was not the case with SA [23]. The presence of a common vulnerability or a similar neurobiological underpinning of OCD and SD was illustrated by a recent case study using nucleus accumbens (NAc) deep brain stimulation (DBS). The study reported unintended, effortless smoking cessation in a nicotine-dependent patient treated with NAc DBS for treatment-resistant OCD [40]. It has been suggested that compulsivity is related to the brain reward system in which dopamine plays an important role. Reduced availability of dopamine receptors, especially D2 receptors, in the striatum has been shown to correlate with increased compulsivity in substance use disorders [5,4144]. Moreover, similar processes have been seen in so-called behavioural addictions such as pathological gambling [45,46] and obesity [47]. Similarly, a recent study has shown decreased baseline [11C]-raclopride binding to striatal D2/3 receptors in OCD patients (Denys et al. 2011, unpublished data), supporting the hypothesis of dopaminergic dysfunction and decreased receptor density in OCD [48,49]. The overlap of decreased dopamine receptor density in addiction as well in OCD strengthens the idea of a common vulnerability [50]. Further research is needed to substantiate this hypothesis, as phenomenological resemblances between disorders do not necessarily reect neurobiological communalities. The strengths of the current study are the large representative general population sample and the use of validated instruments, administered by well-trained interviewers. However, there are also some limitations to the study design that deserve comment. First, because OCD is a relatively rare disorder, even with the large sample size of NEMESIS, conclusions about the relation between OCD and SUD in the general population are based on relatively small numbers, especially when stratied by gender. Secondly, the OCD section of CIDI has limitations, in that it is necessary to be cautious about interpreting CIDI items as DSM criteria. Other instruments might yield different results. However, the CIDI has been well validated against other structured interviews. In addition, the CIDI does not necessarily catch all obsessions; for example, intrusive urges or hoarding behaviours. This could underestimate the prevalence of obsessions. Fourthly, the relatively small numbers precluded the adjustment of the observed relationships for potential confounders (with the exception of gender through stratication). Fifthly, only internalizing Axis I disorders are considered as comorbid
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disorders. As SUD is highly comorbid with externalizing disorders, this might have underestimated the co-occurrence of psychiatric disorders and SUD (e.g. [51,52]). In addition, the CIDI 1.1 assesses only internalizing disorders and none of the externalizing disorders other than SUD (e.g. adult ADHD). Lastly, the current study did not distinguish between various SUDs due to power issues. In the NESARC study [18] the co-occurrence of drug use disorders and anxiety disorders was higher than for alcohol use disorders. Given the strong similarities in design between the NESARC and the NEMESIS study, we hypothesize that the strong association between SD and OCD in the current study is due largely to the relative association between OCD and drug use disorders. In summary, this representative community study showed that the probability of life-time co-occurrence of SD in OCD is higher than in other internalizing DSM disorders, especially in men. These epidemiological data support the idea that substance use disorders especially SD, and OCD, may have a common biological vulnerability or a common neurobiological underpinning resulting in overlapping symptoms and a relatively high level of comorbidity. This also means that patients with OCD (especially men) should always be screened for the presence of alcohol or drug dependence and treated for these disorders when indicated. Declarations of interest None. References
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