CNS Spectrums (2015), 20, 474–478. © Cambridge University Press 2014 doi:10.1017/S1092852914000339
ORIGINAL RESEARCH
Differences in duration of untreated illness, duration, and severity of illness among clinical phenotypes of obsessive-compulsive disorder Bernardo Dell’Osso,* Beatrice Benatti, Lucio Oldani, Gregorio Spagnolin and A. Carlo Altamura Dipartimento di Fisiopatologia medico-chirurgica e dei trapianti, Università degli Studi di Milano, Dipartimento di Salute Mentale, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy
Introduction. Obsessive-compulsive disorder (OCD) is a prevalent, disabling, and comorbid condition that is frequently under-recognized and poorly treated. OCD phenotypes may differ in terms of clinical presentation and severity. However, few studies have investigated whether clinical phenotypes differ in terms of latency to treatment (ie, duration of untreated illness[DUI]), duration, and severity of illness. The present study was aimed to quantify the aforementioned variables in a sample of OCD patients. Methods. One hundred fourteen outpatients with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition,
Text Revision (DSM-IV-TR) diagnosis of OCD were recruited, and their main clinical features were Severity of illness was assessed through the Yale–Brown Obsessive Compulsive Scale (Y-BOCS), and phenotypes were identified through the Y-BOCS Symptom Checklist. A one-way analysis of variance test, followed by a Bonferroni post-hoc test, were performed to compare DUI, duration, and severity across subgroups.
collected. the main (ANOVA) of illness
Results. In the whole sample, the mean DUI exceeded 7 years (87.35 ± 11.75 months), accounting for approximately half of the mean duration of illness (172.2 ± 13.36 months). When subjects were categorized into 4 main clinical phenotypes, respectively, aggressive/checking (n = 31), contamination/cleaning (n = 37), symmetry/ordering (n = 32), and multiple phenotypes (n = 14), DUI, duration, and severity of illness resulted significantly higher in the aggressive/checking subgroup, compared to other subgroups (F = 3.58, p < 0.01; F = 3.07, p < 0.01; F = 4.390, p < 0.01). Discussion. In a sample of OCD patients, along with a mean latency to treatment of approximately 7 years, regardless of the phenotype, patients had spent half of their duration of illness (DI) without being treated. DUI, duration, and severity of illness resulted significantly higher in the aggressive/checking subgroup.
Received 4 April 2014; Accepted 16 May 2014; First published online 26 June 2014 Key words: Obsessive compulsive disorder, duration of untreated illness, obsessive compulsive disorder clinical phenotypes.
Introduction Obsessive-compulsive disorder (OCD) is a prevalent, disabling, and comorbid condition that is frequently under-recognized and poorly treated, and is responsible * Address for correspondence: Bernardo Dell’Osso, MD, Assistant Professor of Psychiatry, Department of Psychiatry, University of Milan, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milano, Via Francesco Sforza 35, 20122 Milano, Italy. (Email: [email protected])
for a major reduction of quality of life and significant functional impairment of patients and caregivers.1,2 The lifetime prevalence of OCD ranges approximately between 1–2% of the general population.3 The 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)4 has allocated OCD a separate chapter, which confirms its growing importance as a distinct condition from other anxiety disorders, as well as its closer relation with other disorders (e.g., hoarding, trichotillomania) that are grouped within the same chapter.
DURATION AND SEVERITY OF OCD
Although many patients with a diagnosis of OCD benefit from treatment with a selective serotonin reuptake inhibitor (SSRI), 10–40% of them do not respond to an adequate trial with such medications.5 Factors associated with poor outcome include early onset, comorbidity, and chronic course.6 In addition, a recent study showed that earlier onset of OCD is associated with a peculiar symptom profile that is characterized by specific obsessions content (ie, aggressive content, pathological doubts, hoarding) and compulsions (ie, repeating rituals and cognitive compulsions).7 Furthermore, patients with early onset OCD were generally found to respond more poorly to treatment,8 as well as to monotherapy with anti-obsessional agents.9 In addition, a long duration of illness (DI) was found to be associated with lessened response to SSRIs10 and overall poorer outcome.11 Beyond early onset and long DI, duration of untreated illness (DUI)—defined as the latency between disease onset and first adequate pharmacological treatment— represents a modifiable parameter whose reduction may positively influence the outcome and long-term course of OCD.12,13 In particular, studies investigating DUI in OCD, given the well-established reluctance, for different reasons, of OCD patients to seek help,14,15 have revealed a latency to first pharmacotherapy ranging from 6–8 years,3,16 along with a worse response to treatment in subjects with a longer DUI.17 Such latency to treatment might be explained with the insidious onset and secretiveness and embarrassment associated with OCD, as well as with the specific obsessive contents that characterize some subgroups of patients.6 OCD symptoms, in fact, are remarkably diverse, regarding both clinical presentation and severity, with patients reporting only one or, more often, many symptoms belonging to different phenotypes.18 Studies are, however, conflicting about whether any particular phenotype of OCD is easier to treat or more likely to benefit from a particular treatment.5 For instance, symptom presentation has received growing empirical attention, as studies have revealed that specific phenotypes exhibit different treatment response rates.19 Checking and washing compulsions are the most common forms of ritualistic behavior in clinical samples of OCD from several different countries.20 Regarding socio-demographic characteristics, Khanna and Mukherjee21 reported that patients with aggression/ checking symptoms were more often young, single, and male, as well as more likely to have an early and insidious onset. On the other hand, patients with contamination/ washing symptoms were more likely to be female and housewives, and more likely to experience OCD onset after marriage.21 In order to assess and quantify DUI, DI, and severity of illness across different OCD phenotypes and further
475
characterize them in terms of clinical course and prognosis, we conducted the present naturalistic study.
Methods We recruited 114 consecutive outpatients who were attending the University Department of Psychiatry at the Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, with a diagnosis of OCD, according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR)22 criteria. The sample included subjects with other psychiatric comorbidities. In case of psychiatric comorbidity, however, OCD had to be the primary disorder, causing the most significant distress and dysfunction and providing the primary motivation for seeking help. At the time of the interview, all patients were on a stable pharmacological treatment, prescribed by a psychiatrist, for at least 4 weeks. After gathering patients’ written informed consent to have their clinical charts reviewed for research purposes, diagnoses were obtained through the structured clinical interview based on DSM-IV criteria (SCID I),23 during which patients’ main socio-demographic and clinical characteristics were collected. These included age of onset, illness duration, DUI, main clinical phenotype, and presence of psychiatric comorbidities. Moreover, OCD severity was assessed using the Yale–Brown Obsessive Compulsive Scale (Y-BOCS), and the main clinical phenotypes present at the moment of the interview were identified through the Y-BOCS Symptom Checklist, a list of common obsessions and compulsions that patients could have experienced during their lifetimes.24,25 When available, caregivers, as well as relatives or close friends, were involved in the collection of the clinical history; we used these other sources particularly to gain information regarding the onset phase, since some patients might report recall difficulties. Descriptive analyses of the sample, one-way analysis of variance (ANOVA) test, Bonferroni post-hoc test, and correlation analysis using Pearson product moment coefficient were performed to assess the demographic characteristics of the sample and compare DUI, DI, and Y-BOCS scores across clinical phenotypes. The level of significance was set at 0.05. All the statistical analyses were performed using the Statistical Package for the Social Sciences for Windows software (version 17.0; SPSS Inc., Chicago, IL, USA).
Results The main demographic and clinical variables of the whole sample (n = 114) are summarized in Table 1. The sample showed an equal gender distribution and a mean age of 40.11 ± 14.63 years. The mean DUI (87.35 ± 11.75 months)
476 B. DELL’OSSO ET AL.
TABLE 1. Main socio-demographic and clinical variables of the sample.
Gender Age (years) Age at onset (years) DI (months) DUI (months) YBOCS scores
Checking/aggressive n = 31
Contamination/cleaning n = 37
Symmetry/order n = 32
Multiple phenotype n = 14
Total sample n = 114
M:F = 17:14 40.11 (±7.23) 23.18 (±5.47) 175.98 (±5.44) 90.62 (±10.32) 27.4 (±15.37)
M:F = 15:22 41.34 (±9.37) 22.83 (±6.71) 170.8 (±6.98) 85.41 (±9.54) 24.4 (±12.43)
M:F = 12:20 40.78 (±6.94) 23.51 (±8.65) 171.6 (±8.25) 86.8 (±10.25) 25.8 (±15.44)
M:F = 9:5 41.24 (±8.51) 22.58 (±7.43) 170.5 (±9.85) 85.6 (±11.41) 24.9 (±11.26)
M:F = 53:61 40.11 (±14.63) 23.02 (±2.01) 172.2 (±13.36) 87.35 (±11.75) 25.62 (±6.98)
DUI, duration of untreated illness; DI, duration of illness; YBOCS, Yale-Brown Obsessive-Compulsive Scale. Means ± standard deviations (shown in brackets) are given for continuous variables.
FIGURE 1. DUI and DI in OCD subgroups. One way ANOVA: F = 3.58, p < 0.01; F = 3.07, p < 0.01.
resulted in approximately half of the mean duration of illness (172.2 ± 13.36 months). After assessing patients’ main clinical phenotypes, 4 subgroups were identified: aggressive/checking (n = 31), contamination/cleaning (n = 37), symmetry/ordering (n = 32), and multiple phenotypes (n = 14). Two patients presented with pure obsessions (0.02%); all other patients presented with both obsessions and compulsions. DUI and DI were found to be significantly longer in the aggressive/checking subgroup when compared to the other subgroups (one-way ANOVA: F = 3.58, p < 0.01; F = 3.07, p < 0.01) (Figure 1). No other significant differences among subgroups in terms of DUI and DI were found. A strong, positive correlation between DUI and DI (r = .71, n = 114, p = 0.00) (Figure 3) was found in the whole sample, with a longer DUI associated with a long DI. The coefficient of determination R2 resulted in 50% of shared variance. Y-BOCS scores of the aggressive/checking subgroup were found to be significantly higher than contamination/
FIGURE 2. Y-BOCS scores in the 4 OCD subgroups. One Way ANOVA: F = 4.39, p < 0.01.
cleaning, symmetry/ordering, and multiple phenotype subgroups (one-way ANOVA: F = 4.39, p < 0.01) (Figure 2).
Discussion Among the main findings of the present study, we found that a simple measure of predominant symptoms allowed clinicians to categorize 88% of the subjects into 3 major clinical phenotypes: aggressive/checking, contamination/cleaning, and symmetry/ordering. Our study also revealed that about 12% of participants, comprising the "multiple phenotype" category, could not be easily categorized, which underlines the frequent presence of symptoms belonging to different phenotypes in OCD.26 Regarding the total sample, it should be noted that the mean DUI (approximately 7 years) accounted for half the mean DI (approximately 14 years). This finding seems to be consistent with a previous study that observed that the mean latency to treatment in OCD patients was significantly longer compared to other anxiety disorders.3 In particular, in the study sample, patients had spent half of their disease without an adequate therapy.
DURATION AND SEVERITY OF OCD
800,00 700,00 600,00
DI
500,00 400,00 300,00 200,00 100,00 0,00 0,00
100,00 200,00 300,00 400,00 500,00 600,00 700,00 DUI
FIGURE 3. Pearson correlation analysis between DUI and DI in the aggressive/checking subgroup. A strong, positive correlation between DUI and DI was found in the whole sample, with a longer DUI associated with a long DI. The coefficient of determination R2 resulted in 50% of shared variance (r = .71, n = 114, p = 0.00). DUI, duration of untreated illness; DI, duration of illness.
When the whole sample was subdivided into 4 main clinical phenotypes, DUI and DI were significantly higher in the aggressive/checking subgroup compared to the other subgroups, respectively, contamination/ cleaning, symmetry/ordering, and multiple phenotypes group. In addition, Y-BOCS scores were significantly higher in the aggressive/checking subgroup, compared to the others, suggesting that longer DUI and DI may determine a greater severity of illness. Furthermore, the results showed a strong, positive correlation between DUI and DI in the whole sample, and DUI could explain nearly 50% of the variance of the DI within the sample. Reported results may be interpreted on the basis of previous findings that showed a lower insight for OCD patients with aggressive/checking symptoms. This characteristic may ultimately lead to a longer latency to pharmacological treatment.27 Literature studies, moreover, showed that the aggressive/checking phenotype, compared to other clinical phenotypes, was more frequently associated with psychiatric comorbidities, such as major depressive disorder, which, due to its specific symptomatology, particularly guilt feelings, anhedonia, and apathy, may further increase patients’ reluctance to seek help.27–29 It should be noticed that, in the present study, the mean age of OCD onset and the mean age were similar across the 4 subgroups. Therefore, the highest age at first pharmacological treatment seems to be the main variable responsible for the higher DUI and DI in the aggressive/checkers, compared to the other phenotypes. Moreover, the Y-BOCS scores of aggressive/checkers, reflecting patients' cross-sectional severity of illness, were higher compared to the other subgroups. This result, on one hand, may effectively indicate a greater severity for this phenotype. On the other hand, it may be related to longer DUI and DI per se. In fact, other studies
477
found that the symmetry and hoarding groups were significantly associated with a greater severity of illness. In addition, the hoarding group was significantly more likely to show longer duration of illness and poorer outcome.30 In the present study, however, no pure hoarding patients were part of the sample (patients with hoarding behaviors were included in the group characterized by the presence of multiple phenotypes). In addition, with the publication of DSM-5, hoarding disorder is now considered a distinct disorder, independent from OCD, though it maintains a close link with obsessive-compulsive–related disorders.4 With respect to the literature heterogeneity regarding OCD phenotypes severity, we should note that such a parameter could also be influenced by patients' cultural and geographic backgrounds, since different cultural attitudes and prejudices, related to OCD-specific symptoms, could worsen patients’ distress and anxiety.31 The following methodological limitations should be taken into consideration when interpreting the results of the current study. One is the possible occurrence of recall bias. In fact, particularly when analyzed retrospectively, the assessment of the DUI may not be accurate and implies the need to trust the reliability of patients as well as available relatives. From this perspective, studies on first episode patients who are identified at first hospitalization/psychiatric service are designed the best to reliably assess DUI. Another limitation is the use of a cross-sectional outcome measure, as a longitudinal one would have likely better detected eventual changes in the severity of illness over time. An additional limitation is the relatively limited size of sample subgroups, when divided on the basis of the phenotype. Further studies with larger samples are needed in order to characterize possible culture-related predominant phenotypes. Taken as a whole, the present results on DUI and DI stress the urgent need to establish early diagnosis and treatment programs with better characterization of OCD phenotype, since we have found a relationship between the 2 variables, and given that a longer DI is ultimately associated with a poor outcome in the long-term.
Disclosures The authors do not have anything to disclose.
R E F E R E NC E S : 1. Grabe HJ, Ruhrmann S, Ettelt S, et al. Familiality of obsessivecompulsive disorder in nonclinical and clinical subjects. Am J Psychiatry. 2006; 163(11): 1986–1992. 2. Fontenelle LF, Mendlowicz MV, Versiani M. The descriptive epidemiology of obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2006; 30(3): 327–337.
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3. Dell'Osso B, Camuri G, Benatti B, Buoli M, Altamura AC. Differences in latency to first pharmacological treatment (duration of untreated illness) in anxiety disorders: a study on patients with panic disorder, generalized anxiety disorder and obsessivecompulsive disorder. Early Interv Psychiatry. 2013; 7(4): 374–380. 4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013. 5. Mataix-Cols D, Rauch SL, Manzo PA, Jenike MA, Baer L. Use of factor-analyzed symptom dimensions to predict outcome with serotonin reuptake inhibitors and placebo in the treatment of obsessive-compulsive disorder. Am J Psychiatry. 1999; 156(9): 1409–1416. 6. Dell'Osso B, Benatti B, Buoli M, et al; ICOCS group. The influence of age at onset and duration of illness on long-term outcome in patients with obsessive-compulsive disorder: a report from the International College of Obsessive Compulsive Spectrum Disorders (ICOCS). Eur Neuropsychopharmacol. 2013; 23(8): 865–871. 7. Narayanaswamy JC, Viswanath B, Veshnal Cherian A, Bada Math S, Kandavel T, Janardhan Reddy YC. Impact of age of onset of illness on clinical phenotype in OCD. Psychiatry Res. 2012; 200(2–3): 554–559. 8. Erzegovesi S, Cavallini MC, Cavedini P, Diaferia G, Locatelli M, Bellodi L. Clinical predictors of drug response in obsessivecompulsive disorder. J Clin Psychopharmacol. 2001; 21(5): 488–492. 9. Rosario-Campos MC, Leckman JF, Mercadante MT, et al. Adults with early-onset obsessive-compulsive disorder. Am J Psychiatry. 2001; 158(11): 1899–1903. 10. Storch EA, Larson MJ, Shapira NA, et al. Clinical predictors of early fluoxetine treatment response in obsessive-compulsive disorder. Depress Anxiety. 2006; 23(7): 429–433. 11. Catapano F, Perris F, Masella M, et al. Obsessive-compulsive disorder: a 3-year prospective follow-up study of patients treated with serotonin reuptake inhibitors OCD follow-up study. J Psychiatr Res. 2006; 40(6): 502–510. 12. Dell'Osso B, Buoli M, Hollander E, Altamura AC. Duration of untreated illness as a predictor of treatment response and remission in obsessive-compulsive disorder. World J Biol Psychiatry. 2010; 11(1): 59–65. 13. Altamura AC, Dell'Osso B, D'Urso N, Russo M, Fumagalli S, Mundo E. Duration of untreated illness as a predictor of treatment response and clinical course in generalized anxiety disorder. CNS Spectr. 2008; 13(5): 415–422. 14. Goodwin R, Koenen KC, Hellman F, Guardino M, Struening E. Helpseeking and access to mental health treatment for obsessivecompulsive disorder. Acta Psychiatr Scand. 2002; 106(2): 143–149. 15. Fullana MA, Mataix-Cols D, Caspi A, et al. Obsessions and compulsions in the community: prevalence, interference, helpseeking, developmental stability, and co-occurring psychiatric conditions. Am J Psychiatry.. 2009; 166(3): 329–336. 16. Altamura AC, Buoli M, Albano A, Dell'Osso B. Age at onset and latency to treatment (duration of untreated illness) in patients with
mood and anxiety disorders: a naturalistic study. Int Clin Psychopharmacol. 2010; 25(3): 172–179. 17 Dell’Osso B, Altamura AC. Duration of untreated psychosis and duration of untreated illness: new vistas. CNS Spectr. 2010; 15(4): 238–246. 18. Rasmussen SA, Eisen JL. The epidemiology and clinical features of obsessive compulsive disorder. Psychiatr Clin North Am. 1992; 15(4): 743–758. 19. Alonso P, Menchon JM, Pifarre J, et al. Long-term follow-up and predictors of clinical outcome in obsessive-compulsive patients treated with serotonin reuptake inhibitors and behavioral therapy. J Clin Psychiatry. 2001; 62: 535–554. 20. Fontenelle LF, Mendlowicz MV, Soares ID, Versiani M. Patients with obsessive-compulsive disorder and hoarding symptoms: a distinctive clinical subtype? Compr Psychiatry. 2004; 45(5): 375–383. 21. Khanna S, Mukherjee D. Checkers and washers: valid subtypes of obsessive compulsive disorder. Psychopathology. 1992; 25(5): 283–288. 22. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed text rev Washington, DC: American Psychiatric Association; 2000. 23. First MB, Spitzer RL, Gibbon L, Williams JBV. Structured Clinical Interview for DSM-IV-TR Axis I Disorders. Research Version, Non-Patient Edition (SCID-I/NP). New York: New York State Psychiatric Institute, Biometric Research; 2002. 24. Goodman WK, Price LH, Rasmussen SA, et al. The Yale–Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry. 1989; 46(11): 1006–1011. 25. Goodman WK, Price LH, Rasmussen SA, et al. The Yale–Brown Obsessive Compulsive Scale. II. Validity. Arch Gen Psychiatry. 1989; 46(11): 1012–1016. 26. Denys D, de Geus F, van Megen HJ, Westenberg HG. Symptom dimensions in obsessive-compulsive disorder: factor analysis on a clinician-rated scale and a self-report measure. Psychopathology. 2004; 37(4): 181–189. 27. Hasler G, LaSalle-Ricci VH, Ronquillo JG, et al. Obsessive-compulsive disorder symptom dimensions show specific relationships to psychiatric comorbidity. Psychiatry Res. 2005; 135(2): 121–132. 28. Fontenelle JM, Harrison L, Santana M, Conceição do Rosário M, Versiani M, Fontenelle LF. Correlates of insight into different symptom dimensions in obsessive-compulsive disorder. Ann Clin Psychiatry. 2013; 25(1): 11–16. 29. Prabhu L, Cherian AV, Viswanath B, Kandavel T, Bada Math S, Janardhan Reddy YC. Symptom dimensions in OCD and their association with clinical characteristics and comorbid disorders. Journal of Obsessive-Compulsive and Related Disorders. 2013; 2(1): 14–21. 30. Matsunaga H, Hayashida K, Kiriike N, Maebayashi K, Stein DJ. The clinical utility of symptom dimensions in obsessive-compulsive disorder. Psychiatry Res. 2010; 180(1): 25–29. 31. Williams MT, Elstein J, Buckner E, Abelson J, Himle J. Symptom dimensions in two samples of Africans Americans with obsessivecompulsive disorder. Journal of Obsessive-Compulsive and Related Disorders. 2012; 1(3): 145–152.
ORIGINAL RESEARCH
Differences in duration of untreated illness, duration, and severity of illness among clinical phenotypes of obsessive-compulsive disorder Bernardo Dell’Osso,* Beatrice Benatti, Lucio Oldani, Gregorio Spagnolin and A. Carlo Altamura Dipartimento di Fisiopatologia medico-chirurgica e dei trapianti, Università degli Studi di Milano, Dipartimento di Salute Mentale, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy
Introduction. Obsessive-compulsive disorder (OCD) is a prevalent, disabling, and comorbid condition that is frequently under-recognized and poorly treated. OCD phenotypes may differ in terms of clinical presentation and severity. However, few studies have investigated whether clinical phenotypes differ in terms of latency to treatment (ie, duration of untreated illness[DUI]), duration, and severity of illness. The present study was aimed to quantify the aforementioned variables in a sample of OCD patients. Methods. One hundred fourteen outpatients with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition,
Text Revision (DSM-IV-TR) diagnosis of OCD were recruited, and their main clinical features were Severity of illness was assessed through the Yale–Brown Obsessive Compulsive Scale (Y-BOCS), and phenotypes were identified through the Y-BOCS Symptom Checklist. A one-way analysis of variance test, followed by a Bonferroni post-hoc test, were performed to compare DUI, duration, and severity across subgroups.
collected. the main (ANOVA) of illness
Results. In the whole sample, the mean DUI exceeded 7 years (87.35 ± 11.75 months), accounting for approximately half of the mean duration of illness (172.2 ± 13.36 months). When subjects were categorized into 4 main clinical phenotypes, respectively, aggressive/checking (n = 31), contamination/cleaning (n = 37), symmetry/ordering (n = 32), and multiple phenotypes (n = 14), DUI, duration, and severity of illness resulted significantly higher in the aggressive/checking subgroup, compared to other subgroups (F = 3.58, p < 0.01; F = 3.07, p < 0.01; F = 4.390, p < 0.01). Discussion. In a sample of OCD patients, along with a mean latency to treatment of approximately 7 years, regardless of the phenotype, patients had spent half of their duration of illness (DI) without being treated. DUI, duration, and severity of illness resulted significantly higher in the aggressive/checking subgroup.
Received 4 April 2014; Accepted 16 May 2014; First published online 26 June 2014 Key words: Obsessive compulsive disorder, duration of untreated illness, obsessive compulsive disorder clinical phenotypes.
Introduction Obsessive-compulsive disorder (OCD) is a prevalent, disabling, and comorbid condition that is frequently under-recognized and poorly treated, and is responsible * Address for correspondence: Bernardo Dell’Osso, MD, Assistant Professor of Psychiatry, Department of Psychiatry, University of Milan, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milano, Via Francesco Sforza 35, 20122 Milano, Italy. (Email: [email protected])
for a major reduction of quality of life and significant functional impairment of patients and caregivers.1,2 The lifetime prevalence of OCD ranges approximately between 1–2% of the general population.3 The 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)4 has allocated OCD a separate chapter, which confirms its growing importance as a distinct condition from other anxiety disorders, as well as its closer relation with other disorders (e.g., hoarding, trichotillomania) that are grouped within the same chapter.
DURATION AND SEVERITY OF OCD
Although many patients with a diagnosis of OCD benefit from treatment with a selective serotonin reuptake inhibitor (SSRI), 10–40% of them do not respond to an adequate trial with such medications.5 Factors associated with poor outcome include early onset, comorbidity, and chronic course.6 In addition, a recent study showed that earlier onset of OCD is associated with a peculiar symptom profile that is characterized by specific obsessions content (ie, aggressive content, pathological doubts, hoarding) and compulsions (ie, repeating rituals and cognitive compulsions).7 Furthermore, patients with early onset OCD were generally found to respond more poorly to treatment,8 as well as to monotherapy with anti-obsessional agents.9 In addition, a long duration of illness (DI) was found to be associated with lessened response to SSRIs10 and overall poorer outcome.11 Beyond early onset and long DI, duration of untreated illness (DUI)—defined as the latency between disease onset and first adequate pharmacological treatment— represents a modifiable parameter whose reduction may positively influence the outcome and long-term course of OCD.12,13 In particular, studies investigating DUI in OCD, given the well-established reluctance, for different reasons, of OCD patients to seek help,14,15 have revealed a latency to first pharmacotherapy ranging from 6–8 years,3,16 along with a worse response to treatment in subjects with a longer DUI.17 Such latency to treatment might be explained with the insidious onset and secretiveness and embarrassment associated with OCD, as well as with the specific obsessive contents that characterize some subgroups of patients.6 OCD symptoms, in fact, are remarkably diverse, regarding both clinical presentation and severity, with patients reporting only one or, more often, many symptoms belonging to different phenotypes.18 Studies are, however, conflicting about whether any particular phenotype of OCD is easier to treat or more likely to benefit from a particular treatment.5 For instance, symptom presentation has received growing empirical attention, as studies have revealed that specific phenotypes exhibit different treatment response rates.19 Checking and washing compulsions are the most common forms of ritualistic behavior in clinical samples of OCD from several different countries.20 Regarding socio-demographic characteristics, Khanna and Mukherjee21 reported that patients with aggression/ checking symptoms were more often young, single, and male, as well as more likely to have an early and insidious onset. On the other hand, patients with contamination/ washing symptoms were more likely to be female and housewives, and more likely to experience OCD onset after marriage.21 In order to assess and quantify DUI, DI, and severity of illness across different OCD phenotypes and further
475
characterize them in terms of clinical course and prognosis, we conducted the present naturalistic study.
Methods We recruited 114 consecutive outpatients who were attending the University Department of Psychiatry at the Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, with a diagnosis of OCD, according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR)22 criteria. The sample included subjects with other psychiatric comorbidities. In case of psychiatric comorbidity, however, OCD had to be the primary disorder, causing the most significant distress and dysfunction and providing the primary motivation for seeking help. At the time of the interview, all patients were on a stable pharmacological treatment, prescribed by a psychiatrist, for at least 4 weeks. After gathering patients’ written informed consent to have their clinical charts reviewed for research purposes, diagnoses were obtained through the structured clinical interview based on DSM-IV criteria (SCID I),23 during which patients’ main socio-demographic and clinical characteristics were collected. These included age of onset, illness duration, DUI, main clinical phenotype, and presence of psychiatric comorbidities. Moreover, OCD severity was assessed using the Yale–Brown Obsessive Compulsive Scale (Y-BOCS), and the main clinical phenotypes present at the moment of the interview were identified through the Y-BOCS Symptom Checklist, a list of common obsessions and compulsions that patients could have experienced during their lifetimes.24,25 When available, caregivers, as well as relatives or close friends, were involved in the collection of the clinical history; we used these other sources particularly to gain information regarding the onset phase, since some patients might report recall difficulties. Descriptive analyses of the sample, one-way analysis of variance (ANOVA) test, Bonferroni post-hoc test, and correlation analysis using Pearson product moment coefficient were performed to assess the demographic characteristics of the sample and compare DUI, DI, and Y-BOCS scores across clinical phenotypes. The level of significance was set at 0.05. All the statistical analyses were performed using the Statistical Package for the Social Sciences for Windows software (version 17.0; SPSS Inc., Chicago, IL, USA).
Results The main demographic and clinical variables of the whole sample (n = 114) are summarized in Table 1. The sample showed an equal gender distribution and a mean age of 40.11 ± 14.63 years. The mean DUI (87.35 ± 11.75 months)
476 B. DELL’OSSO ET AL.
TABLE 1. Main socio-demographic and clinical variables of the sample.
Gender Age (years) Age at onset (years) DI (months) DUI (months) YBOCS scores
Checking/aggressive n = 31
Contamination/cleaning n = 37
Symmetry/order n = 32
Multiple phenotype n = 14
Total sample n = 114
M:F = 17:14 40.11 (±7.23) 23.18 (±5.47) 175.98 (±5.44) 90.62 (±10.32) 27.4 (±15.37)
M:F = 15:22 41.34 (±9.37) 22.83 (±6.71) 170.8 (±6.98) 85.41 (±9.54) 24.4 (±12.43)
M:F = 12:20 40.78 (±6.94) 23.51 (±8.65) 171.6 (±8.25) 86.8 (±10.25) 25.8 (±15.44)
M:F = 9:5 41.24 (±8.51) 22.58 (±7.43) 170.5 (±9.85) 85.6 (±11.41) 24.9 (±11.26)
M:F = 53:61 40.11 (±14.63) 23.02 (±2.01) 172.2 (±13.36) 87.35 (±11.75) 25.62 (±6.98)
DUI, duration of untreated illness; DI, duration of illness; YBOCS, Yale-Brown Obsessive-Compulsive Scale. Means ± standard deviations (shown in brackets) are given for continuous variables.
FIGURE 1. DUI and DI in OCD subgroups. One way ANOVA: F = 3.58, p < 0.01; F = 3.07, p < 0.01.
resulted in approximately half of the mean duration of illness (172.2 ± 13.36 months). After assessing patients’ main clinical phenotypes, 4 subgroups were identified: aggressive/checking (n = 31), contamination/cleaning (n = 37), symmetry/ordering (n = 32), and multiple phenotypes (n = 14). Two patients presented with pure obsessions (0.02%); all other patients presented with both obsessions and compulsions. DUI and DI were found to be significantly longer in the aggressive/checking subgroup when compared to the other subgroups (one-way ANOVA: F = 3.58, p < 0.01; F = 3.07, p < 0.01) (Figure 1). No other significant differences among subgroups in terms of DUI and DI were found. A strong, positive correlation between DUI and DI (r = .71, n = 114, p = 0.00) (Figure 3) was found in the whole sample, with a longer DUI associated with a long DI. The coefficient of determination R2 resulted in 50% of shared variance. Y-BOCS scores of the aggressive/checking subgroup were found to be significantly higher than contamination/
FIGURE 2. Y-BOCS scores in the 4 OCD subgroups. One Way ANOVA: F = 4.39, p < 0.01.
cleaning, symmetry/ordering, and multiple phenotype subgroups (one-way ANOVA: F = 4.39, p < 0.01) (Figure 2).
Discussion Among the main findings of the present study, we found that a simple measure of predominant symptoms allowed clinicians to categorize 88% of the subjects into 3 major clinical phenotypes: aggressive/checking, contamination/cleaning, and symmetry/ordering. Our study also revealed that about 12% of participants, comprising the "multiple phenotype" category, could not be easily categorized, which underlines the frequent presence of symptoms belonging to different phenotypes in OCD.26 Regarding the total sample, it should be noted that the mean DUI (approximately 7 years) accounted for half the mean DI (approximately 14 years). This finding seems to be consistent with a previous study that observed that the mean latency to treatment in OCD patients was significantly longer compared to other anxiety disorders.3 In particular, in the study sample, patients had spent half of their disease without an adequate therapy.
DURATION AND SEVERITY OF OCD
800,00 700,00 600,00
DI
500,00 400,00 300,00 200,00 100,00 0,00 0,00
100,00 200,00 300,00 400,00 500,00 600,00 700,00 DUI
FIGURE 3. Pearson correlation analysis between DUI and DI in the aggressive/checking subgroup. A strong, positive correlation between DUI and DI was found in the whole sample, with a longer DUI associated with a long DI. The coefficient of determination R2 resulted in 50% of shared variance (r = .71, n = 114, p = 0.00). DUI, duration of untreated illness; DI, duration of illness.
When the whole sample was subdivided into 4 main clinical phenotypes, DUI and DI were significantly higher in the aggressive/checking subgroup compared to the other subgroups, respectively, contamination/ cleaning, symmetry/ordering, and multiple phenotypes group. In addition, Y-BOCS scores were significantly higher in the aggressive/checking subgroup, compared to the others, suggesting that longer DUI and DI may determine a greater severity of illness. Furthermore, the results showed a strong, positive correlation between DUI and DI in the whole sample, and DUI could explain nearly 50% of the variance of the DI within the sample. Reported results may be interpreted on the basis of previous findings that showed a lower insight for OCD patients with aggressive/checking symptoms. This characteristic may ultimately lead to a longer latency to pharmacological treatment.27 Literature studies, moreover, showed that the aggressive/checking phenotype, compared to other clinical phenotypes, was more frequently associated with psychiatric comorbidities, such as major depressive disorder, which, due to its specific symptomatology, particularly guilt feelings, anhedonia, and apathy, may further increase patients’ reluctance to seek help.27–29 It should be noticed that, in the present study, the mean age of OCD onset and the mean age were similar across the 4 subgroups. Therefore, the highest age at first pharmacological treatment seems to be the main variable responsible for the higher DUI and DI in the aggressive/checkers, compared to the other phenotypes. Moreover, the Y-BOCS scores of aggressive/checkers, reflecting patients' cross-sectional severity of illness, were higher compared to the other subgroups. This result, on one hand, may effectively indicate a greater severity for this phenotype. On the other hand, it may be related to longer DUI and DI per se. In fact, other studies
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found that the symmetry and hoarding groups were significantly associated with a greater severity of illness. In addition, the hoarding group was significantly more likely to show longer duration of illness and poorer outcome.30 In the present study, however, no pure hoarding patients were part of the sample (patients with hoarding behaviors were included in the group characterized by the presence of multiple phenotypes). In addition, with the publication of DSM-5, hoarding disorder is now considered a distinct disorder, independent from OCD, though it maintains a close link with obsessive-compulsive–related disorders.4 With respect to the literature heterogeneity regarding OCD phenotypes severity, we should note that such a parameter could also be influenced by patients' cultural and geographic backgrounds, since different cultural attitudes and prejudices, related to OCD-specific symptoms, could worsen patients’ distress and anxiety.31 The following methodological limitations should be taken into consideration when interpreting the results of the current study. One is the possible occurrence of recall bias. In fact, particularly when analyzed retrospectively, the assessment of the DUI may not be accurate and implies the need to trust the reliability of patients as well as available relatives. From this perspective, studies on first episode patients who are identified at first hospitalization/psychiatric service are designed the best to reliably assess DUI. Another limitation is the use of a cross-sectional outcome measure, as a longitudinal one would have likely better detected eventual changes in the severity of illness over time. An additional limitation is the relatively limited size of sample subgroups, when divided on the basis of the phenotype. Further studies with larger samples are needed in order to characterize possible culture-related predominant phenotypes. Taken as a whole, the present results on DUI and DI stress the urgent need to establish early diagnosis and treatment programs with better characterization of OCD phenotype, since we have found a relationship between the 2 variables, and given that a longer DI is ultimately associated with a poor outcome in the long-term.
Disclosures The authors do not have anything to disclose.
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