Symptom dimensions in OCD and their association with clinical characteristics and comorbid disorders

Journal of Obsessive-Compulsive and Related Disorders 2 (2013) 14–21

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Symptom dimensions in OCD and their association with clinical characteristics and comorbid disorders Lokesh Prabhu, Anish V. Cherian, Biju Viswanath, Thennarasu Kandavel, Suresh Bada Math, Y.C. Janardhan Reddy n Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India

a r t i c l e i n f o

a b s t r a c t

Article history: Received 4 June 2012 Received in revised form 13 October 2012 Accepted 15 October 2012 Available online 26 October 2012

The complex clinical phenotype of obsessive–compulsive disorder (OCD) can be summarized in to a few temporally stable and consistent symptom dimensions that may have distinct clinical and neurobiological correlates. We examined the relationship between symptom dimensions and clinical characteristics in 161 consecutive patients with DSM-IV diagnosis of OCD with the Yale–Brown Obsessive– Compulsive Scale severity score of Z 20 recruited from a specialty OCD clinic in India. Clinician administered version of the Dimensional-Yale–Brown Obsessive–Compulsive Scale (D-YBOCS) was used to assess symptom dimensions. Earlier age of onset of OCD was associated with sexual/religious, aggression and symmetry dimensions. Fear of contamination was associated with female sex, higher family loading, greater severity of illness, poorer insight, and somewhat poorer functioning and lower physical quality of life. Aggression dimension was associated with presence of anxiety disorders and social phobia in particular. Our study demonstrates relatively specific associations between OCD symptom dimensions and clinical characteristics supporting the view that symptom dimensions could be employed to reduce the heterogeneity of OCD. The study encourages research on neurobiological and genetic underpinnings of symptom dimensions and supports inclusion of symptom dimensions in characterizing OCD in DSM-5 text. & 2012 Elsevier Inc. All rights reserved.

Keywords: Obsessive–compulsive disorder Symptom dimension Dimensional YBOCS Comorbidity Heterogeneity

1. Introduction The exact etiology of obsessive–compulsive disorder (OCD) is unknown. Systematic search for the genetic basis of OCD has not yielded any meaningful and replicable findings (Grados, Walkup, & Walford, 2003; Samuels, 2009). This is possibly due to the heterogeneous nature of OCD (Miguel et al., 2005; Samuels, 2009; Stein, 2000). Given this heterogeneity, there have been various attempts to subtype OCD into homogenous entities using clinical phenomenological characteristics such as age at onset of OCD (Hemmings et al., 2004), comorbidity profile (e.g. tic disorders) (Miguel, do Rosario-Campos, Shavitt, Hounie, & Mercadante, 2001), familiality (Viswanath, Narayanaswamy, Cherian, Reddy, & Math, 2011) and recently symptom dimensions (Mataix-Cols, Rosario-Campos, & Leckman, 2005). There is wide variation in the thematic content of obsessions and compulsions. Empirical evidence suggests that the diversity in OCD symptoms can be reduced to a fewer number of symptom dimensions; as a result OCD is increasingly seen as a dimensional

n

Corresponding author. Tel.: þ91 80 269 95278. E-mail address: [email protected] (Y.C. Janardhan Reddy).

2211-3649/$ - see front matter & 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jocrd.2012.10.002

disorder (Mataix-Cols et al., 2005). Most widely used approach to reduce the heterogeneity is to generate symptom dimensions based on the factor analysis of the symptoms such as the ones generated by the Yale–Brown Obsessive–Compulsive Scale (YBOCS) symptom checklist (Goodman et al., 1989). A recent meta-analysis of 21 factor analytic studies of the YBOCS symptom checklist involving 5124 participants identified four symptom dimensions: (a) symmetry obsessions; counting, ordering and arranging compulsions; (b) forbidden thoughts (aggressive, sexual, religious and somatic obsessions; and related checking compulsions); (c) contamination/cleaning, and (d) hoarding (Bloch, Landeros-Weisenberger, Rosario, Pittenger, & Leckman, 2008). These symptom dimensions have been reported to be temporally (Mataix-Cols et al., 2002) and cross-culturally stable (Matsunaga et al., 2008), with distinct neural correlates (Mataix-Cols et al., 2004) and comorbidity patterns (Hasler et al., 2005). Brain-imaging and genetic studies have also provided preliminary evidence for the biological validity of these dimensions (Gilbert et al., 2008; Hashimoto et al., 2011; van den Heuvel et al., 2009). There is also some evidence that symptom dimensions may have specific relationships with certain clinical characteristics such as age of onset and comorbid patterns. An integration of

L. Prabhu et al. / Journal of Obsessive-Compulsive and Related Disorders 2 (2013) 14–21

symptom dimensions with clinical characteristics may help identify homogeneous subtypes that may in turn help in elucidating the neurobiological and genetic underpinnings of OCD. However, very few studies have systematically examined the relationship between specific symptom dimensions and clinical characteristics. A recent study using factor and cluster analytic analyses to establish symptom dimensions, found associations between factor I (aggressive, sexual, religious and somatic obsessions, checking compulsions) and co-morbid anxiety disorders/ depression, factor II (obsessions of symmetry, repeating, counting and arranging/ordering compulsions) and co-morbid bipolar disorders/panic disorder/agoraphobia and factor III (obsessions of contamination and washing compulsions) and tics/eating disorders (Hasler et al., 2005). In addition, factor I and factor II were associated with early onset of OCD. In a Brazilian study that examined the trajectory of comorbid psychiatric disorders associated with OCD according to the first manifested disorder, those who presented with separation anxiety disorder as first diagnosis had higher scores on the sexual/religious dimension of the Dimensional-Yale–Brown Obsessive–Compulsive Scale (D-YBOCS) (Rosario-Campos et al., 2006) and on the measures of anxiety depression, and a higher frequency of post-traumatic disorder (de Mathis et al., 2012). In another large Brazilian study, tic-related OCD was associated with more severe scores on the aggressive, sexual/religious and hoarding symptom dimensions of the D-YBOCS in addition to its association with early onset, male preponderance, sensory phenomena, and comorbidity with anxiety and impulse control disorders and attention deficit hyperactivity disorder (de Alvarenga et al., 2012). Association between aggressive dimension and Tourette syndrome has also been reported in a study from Japan (Kano et al., 2012). This study aimed to examine the relationships between symptom dimensions and clinical characteristics such as age of onset, comorbidity, familiality and insight using the D-YBOCS (Rosario-Campos et al., 2006). The scale summarizes complex OCD phenotype into a few consistent and temporally stable symptom dimensions. It is a reliable and valid instrument to assess multiple aspects of OCD symptom severity (RosarioCampos et al., 2006). The D-YBOCS is a more appropriate instrument to assess various symptom dimensions and their severity than the conventional statistical method of factor analysis of symptom checklists. Conventional instruments such as the Y–BOCS assess obsessions and compulsions separately and generate total severity score instead of generating severity of individual dimensions. The D-YBOCS assesses OCD symptoms within six distinct dimensions that combine thematically related obsessions and compulsions. The instrument allows classifying same type of ritual under different symptom dimensions based on the functionality of the ritual rather than just the form of it. For example, checking can be secondary sexual/religious, aggressive, somatic or even contamination obsessions. Severity ratings individual symptom dimensions are reported to be largely independent of each other with only modest correlation with global severity. Accordingly, the D-YBOCS may be better suited than other symptom measures for investigating the relationship between OCD symptom dimensions and clinical characteristics. Based on the limited literature on the relation between symptom dimensions, we hypothesized distinctive association between certain symptom dimensions and clinical characteristics. Specifically, we expected aggression, symmetry and sexual/religious dimensions to be associated with early onset; and aggression and sexual/religious dimensions to be comorbid with anxiety and depressive disorders. Although the literature suggests specific relation between impulse control disorders, tic disorders, and eating disorders with certain symptom dimensions, we refrained from hypothesizing such a relationship in view of low rates of

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these disorders in our OCD samples (Jaisoorya, Janardhan Reddy, & Srinath, 2003; Viswanath et al., 2012).

2. Method The ethics committee of the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India approved the study with respect to ethical aspects. All patients gave written informed consent. From May 2009 to July 2010, 253 new patients with a primary diagnosis of OCD as per DSM-IV criteria were registered at the specialty OCD clinic of the NIMHANS. We included only those subjects between age 18 and 60 years with YBOCS score of Z20. We included only those subjects with a YBOCS score of Z20 to ensure that our sample represented at least moderately ill patients. A score of Z20 on the YBOCS is generally indicative of at least moderately severe OCD (The Clomipramine Collaborative Study Group, 1991) and a similar criterion has been employed in some clinical trials (e.g., Koran, Hackett, Rubin, Wolkow, & Robinson, 2002). Of the 253 patients with a primary diagnosis of OCD, only 204 subjects had a score of Z20 on the YBOCS. Of these, only 161 patients could be assessed as 43 patients were unwilling to participate or unable to come for assessments. The patients who participated did not differ significantly from those who did not with respect to age, sex, age at onset, duration of illness and YBOCS total score. All the patients who participated in this study were consecutive new attendees of the specialty OCD clinic who continued to receive standard care in the clinic even after assessments for this study. The standard care included psychoeducation, treatment with Serotonin Reuptake Inhibitors (SRIs) and behavior therapy in the form exposure and response prevention or augmentation with drugs (mostly atypical antipsychotic drugs and benzodiazepines) to partial responders or non-responders to SRIs. The treatment was decided by the senior consultants of the clinic (YCJR or BMS). Trained post-graduate residents in psychiatry evaluated all subjects initially using a topical OCD work-up pro forma specially developed for the purpose of clinical assessment of subjects in the OCD clinic. It includes demographic characteristics, clinical features (e.g., age of onset of symptoms, duration of illness, etc.), detailed narrative of the obsessive–compulsive and other psychiatric symptoms, family history of mental illnesses (OCD in particular), mental status examination and DSM-IV diagnoses. They were also administered the MINI International Neuropsychiatric Interview plus (M.I.N.I. PLUS, version 5.0) (Sheehan et al., 1998), and the tic disorder subsection of the MINI—KID (Sheehan et al., 1998) to confirm a diagnosis of OCD and comorbid disorders. Obsessive–compulsive symptom profile and severity was assessed with the YBOCS checklist and the severity rating scale including item  11 for insight (Goodman et al., 1989). Global severity of OCD was assessed with the Clinical Global Impression-Severity (CGI-S) scale (Guy, 2010). A senior consultant (YCJR or SBM) established the diagnosis and associated clinical characteristics by interviewing the patient and by consensus by reviewing all the information so obtained. A family history of OCD in first-degree relatives of the index patient was determined by specifically asking if any of their relative had been diagnosed to have OCD, or was suffering from classical symptoms of OCD as was described in the OCD section of the M.I.N.I. PLUS or in the Y–BOCs checklist. At least two informants (the index patient and his/her first degree relative, usually a parent) provided history in support of a diagnosis of OCD in the relatives of an index patient. Since the index patient and the relative become aware of symptoms of OCD in the process of evaluation, we considered this method to be the most practical method of obtaining family history of OCD in first-degree relatives. The principal author and the second author evaluated all patients with the clinician administered version of the D-YBOCS, the Structured Clinical Interview for DSM IV Axis II disorders (SCID-II) (Maffei et al., 1997), the Global Assessment of Functioning scale (GAF), and the WHO Quality of life-BREF (WHOQOL-BREF) (WHO, 1996). The principal author and the second author had been trained in administering these instruments by a senior consultant of the OCD clinic (YCJR). However, no formal reliability exercises were carried out. In the D-YBOCS, obsessions and compulsions are divided into seven different symptom dimensions: contamination/cleaning, symmetry/ordering/arranging/ counting, sexual/religious, aggression, somatic, hoarding/collecting and miscellaneous obsessions and compulsions. Severity for each dimension is measured on three ordinal scales with six anchor points that focus on symptom frequency (0–5), the amount of distress they cause (0–5) and the degree to which they interfere with functioning (0–5) during the previous week. Global symptom severity is estimated using the above three ordinal scales (0–15). The overall impairment due to symptoms is assessed on a scale of ‘none’ (0 points) to ‘severe’ (15 points). The total global score is obtained by combining the sum of the global symptom severity scores for frequency, distress and interference (0–15) and the overall impairment score (0–15), yielding a maximum total global severity score of 30. A study by Rosario-Campos et al. (2006) showed high correlations between the self-report and expert rating of severity, suggesting that either version could be used alone. In our study we have used the clinician administered version of the instrument. On the YBOCS item-11 insight scale, the insight is graded as follows: 0¼excellent, 1 ¼good insight, 2¼ fair insight, 3 ¼poor insight (overvalued ideas),

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4¼ lacks insight (delusional). A higher score on the Y–BOCS item-11 indicates poorer insight. In the present study a score 0, 1 or 2 was considered as indicative of good insight and a score of 3 or 4 was considered as poor insight (Matsunaga et al., 2002).

2.1. Statistical analysis The data was tested for normative distribution using Shapiro–Wilk test. Since the data was not normatively distributed, we used Mann Whitney U test for comparison of continuous variables and Spearman’s correlation for assessing the correlation between severity of symptom dimensions and clinical variables. Effect of gender was analyzed using general linear model of univariate analysis of covariance with age, age of onset and gender as covariates. For univariate analyses, significance was set at a conservative value of r 0.01 in view of the exploratory nature of the study. Influence of severity of symptom dimensions on co-morbid conditions was determined using logistic regression analyses. Associations between OCD symptom dimensions and psychiatric comorbidity were expressed as odds ratios derived from binary logistic regression with the psychiatric comorbid condition as the binary response variable, and the seven symptom dimensions, age, age of onset and sex as independent variables. Statistical Package for Social Sciences (SPSS), version 15 (SPSS Inc., Chicago, IL, USA) was used for the analysis.

3. Results 3.1. Clinical characteristics Demographic and clinical characteristics are shown in Table 1. Most common symptoms were fear of contamination and washing compulsions. Number of subjects presenting obsessive– compulsive symptoms in each of the D-YBOCS dimensions is as following: contamination (n ¼106, 66%), symmetry and ordering (n¼89, 55%), sexual and religious (n¼ 67, 42%), aggression (n¼ 53, 33%), collecting and hoarding (n ¼13, 8%), somatic (n ¼4, 3%), and miscellaneous (n ¼57, 35%). Less than half of the subjects had juvenile onset of OCD. Severity scores of the symptom dimensions as per the D-YBOCS are shown in Table 2. Contamination was not only the most common symptom dimension but also the one with highest severity score. The mean total global score was 22 indicating that the patients were severely ill. Spearman’s correlation between symptom dimensions revealed that contamination was negatively correlated with aggression (rho ¼  0.206, p ¼0.01), sexual/religious dimension (forbidden thoughts) (rho¼  0.325, p o0.001) and miscellaneous dimension (rho¼  0.480, po0.001), while there was a significant positive correlation between symmetry and hoarding dimensions (rho¼0.264, p o0.001), as well as aggression and somatic dimensions (rho ¼0.188, p ¼0.02). Any Axis I comorbid disorder was found in 91 (57%) subjects. Major depressive disorder (MDD) was the most common comorbid Axis I disorder followed by social phobia and generalized anxiety disorder (Table 3). Obsessive– compulsive and anxious-avoidant personality disorders were the most common Axis II disorders (Table 3). 3.2. Relationship between symptom dimensions and clinical characteristics Age of onset negatively correlated with score on sexual/ religious dimension with a trend toward negative correlation with symmetry and aggression. Age negatively correlated with sexual/religious dimension with a trend toward negative correlation with aggression dimension. Those with juvenile onset OCD when compared to late onset had greater severity scores on the sexual/religious (4.99 75.11 vs. 2.6074.21, U ¼2416.5, p ¼0.002) and symmetry (4.6274.24 vs. 3.0173.82, U ¼2541.5, p ¼0.01) dimensions with only a trend toward higher score on hoarding dimension (0.53 71.45 vs. 0.1870.96, U¼2953.5, p¼ 0.04) (Table 4).

Table 1 Demographic and clinical characteristics (n¼ 161). Variable

Value

Age, mean (SD)

28.85 (8.99)

Age of onset, mean (SD)

20.03 (6.66)

Duration of illness in years, mean (SD) Number of years of education, mean (SD)

9.19 (7.28) 13.44 (3.13)

Gender, n (%) Male Female

90 (55.9) 71 (44.1)

Marital status, n (%) Single Married Separated

91 (56.5) 69 (42.9) 1 (0.6)

Domicile, n (%) Rural Urban

33 (20.5) 128 (79.5)

Juvenile onset (r 18 years), n (%)

79 (49.1)

History of OCD in first-degree relatives, n (%)

18 (11.2)

Obsessions (Y–BOCS checklist), n (%) Contamination Somatic Aggressive Sexual Religious Pathological doubts Need for symmetry Hoarding Miscellaneous

105 4 53 35 49 78 34 13 58

(65.2) (2.5) (32.9) (21.7) (30.4) (48.4) (21.1) (8.1) (36.0)

Compulsions (Y–BOCS checklist), n (%) Washing Checking Repeating Counting Collecting Ordering Miscellaneous

115 90 90 31 13 38 57

(71.4) (55.9) (55.9) (19.3) (8.1) (23.6) (35.4)

Y–BOCS severity scores, mean (SD) Obsessions Compulsions Total

14.55 (2.67) 13.85 (3.06) 28.44 (5.05)

Y–BOCS insight, n (%) Good Poor

146 (90.7) 15 (9.3)

Clinical Global Impression-Severity, mean (SD)

4.81 (0.69)

Quality of life, mean (SD) Physical Psychological Social Environmental

39.22 47.54 67.39 64.42

Global Assessment of Functioning score, mean (SD)

60.12 (8.88)

(11.23) (7.18) (10.47) (6.62)

The Y–BOCS insight score positively correlated with severity scores on contamination and hoarding dimensions. There was a trend for those with poor insight to have scored higher on the contamination dimension (9.874.86 vs. 6.6675.34, U ¼722, p¼0.027) than those with good insight. Familial OCD patients were more likely to have higher severity scores in the contamination dimension than non-familial patients (10.974.3 vs. 6.4575.29, U ¼585.5, po0.001). On the other hand, non-familial OCD patients had higher scores in the miscellaneous dimension (3.7175.05 vs. 0.7273.06, U ¼868.5, p¼0.009) than the familial group. In the general linear model of univariate analysis of covariance with age, age of onset and gender as covariates, female sex

L. Prabhu et al. / Journal of Obsessive-Compulsive and Related Disorders 2 (2013) 14–21

Table 2 Severity scores of symptom dimensions as per the D-YBOCS (n ¼161). Dimensions

Aggression Sexual and religious Symmetry, ordering, arranging, counting Contamination Collecting and hoarding Somatic Miscellaneous Global symptom severity Clinician rating of impairment Total global severity score

Mean severity score

Standard Range of score deviation (minimum and maximum)

3.07 3.77 3.80

4.67 4.81 4.10

0–14 0–15 0–14

6.95 0.35 0.15 3.37 12.24 10.12 22.43

5.36 1.24 1.03 4.95 1.71 2.04 3.12

0–15 0–6 0–10 0–15 0–15 6–15 12–30

regression analysis. The severity scores on each of the seven symptom dimensions of the D-YBOCS, age, gender and age of onset were entered as independent variables. Only the aggression dimension was positively associated with the presence of any anxiety disorder and social phobia. Contamination had a significant positive correlation with CGI-S (rho¼0.28, po0.001), and a trend toward negative correlation with GAF (rho¼  0.16, po0.05). Somatic dimension showed a trend toward negative correlation with psychological domain of quality of life (rho¼ 0.169, p¼0.03).

4. Discussion

Table 3 Current Axis I and II comorbid disorders (n¼ 161). Axis I disorders

n (%)

Mood disorders Major depressive disorder Dysthymia Bipolar disorder

36 (22.4) 19 (11.8) 1 (0.6)

Anxiety disorders Social phobia Generalized Anxiety Disorder Panic disorder Agoraphobia Specific phobia Any anxiety disorder

18 10 7 3 2 35

Suicidal behavior Life time suicidal attempt Suicidality

13 (8.1) 4 (2.5)

(11.2) (6.2) (4.3) (1.9) (1.2) (21.7)

Alcohol/substance use Alcohol dependence syndrome Non-alcoholic psychoactive substance dependence

1 (0.6) 5 (3.1)

Other disordersn Somatization disorder Chronic motor/vocal tics Body dysmorphic disorder Hypochondriasis Tourette’s disorder

3 4 2 1 1

Axis II disorders Obsessive–compulsive PD Anxious avoidant PD Borderline PD Schizoid PD Schizotypal PD Dependent PD

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(1.9) (2.5) (1.2) (0.6) (0.6)

n (%) 25 (15.5) 15 (9.3) 3 (1.9) 1 (0.6) 2 (1.2) 1 (0.6)

n There were no patients with comorbid eating disorders, psychosis, PTSD, and certain personality disorders (histrionic, antisocial, passive aggressive, depressive, and paranoid).

was associated with contamination dimension [F(1,157) ¼15.13, p o0.001]. We examined association of symptom dimensions with comorbid disorders using the binary logistic regression analysis (Table 5). In the logistic regression analysis, the following comorbid disorders were individually used as binary response variables: major depression, dysthymia, social phobia, generalized anxiety disorder, panic disorder, any anxiety disorder, anxious avoidant personality disorder and obsessive–compulsive personality disorder. These were the common comorbid disorders present in at least 5% of the sample. Rarer diagnoses were excluded from

We aimed to examine the relationship between symptom dimensions in OCD and clinical characteristics using a newly developed dimensional scale of OCD. Our study is one of the first studies to use the D-YBOCS to assess patients’ individual symptom dimensions. Our study found that earlier age of onset was associated with sexual/religious, aggression and symmetry dimensions; fear of contamination with female sex, higher family loading, greater severity of illness, and somewhat poorer insight and functioning; and higher score on aggression dimension was associated with presence of anxiety disorders. Association of earlier age of onset with sexual/religious, aggression and symmetry dimension is in accordance with the findings of Hasler et al. (2007) and others (Denys, de Geus, van Megen, & Westenberg, 2004; Hemmings et al., 2004; Jaisoorya et al., 2003; March & Leonard, 1996; Millet et al., 2004). A recent study of 545 OCD subjects from our center reported association between early onset and sexual, aggressive, pathological doubts, hoarding, repeating rituals and miscellaneous symptoms (Narayanaswamy et al., 2012). In a study by Alsobrook, Leckman, Goodman, Rasmussen, and Pauls (1999), OCD probands with high scores on aggression/sex/ religion or symmetry/ordering dimensions were twice as likely to have first-degree relative with OCD compared to those individuals with low scores on these factors. In a study by Hasler et al., sibling–sibling correlations were statistically significant for all four symptom dimensions. The hoarding dimension (Factor IV) seemed as the most familial, followed by the aggressive, sexual, and religious obsessions and checking compulsions (Factor I), although small, but still significant familiality was found for Factor II (symmetry) and Factor III (contamination) (Hasler et al., 2007). Using the Tourette Syndrome Association International Consortium for Genetics (TSAICG) data set, Zhang et al. (2002) analyzed genotypic data from a genome scan that used the hoarding factor as a quantitative phenotype and found significant allele sharing for markers at 4q34–35, 5q35.2–35.3, and 17q25. The above evidence indicates that hoarding is most familial followed by aggression/sex/religious and symmetry dimensions. However, in our study, those with familial OCD had significantly higher scores on contamination dimension, whereas those with non-familial OCD had higher scores on the miscellaneous dimension. Association between contamination dimension and female sex is in accordance with results of previous studies (Bogetto, Venturello, Albert, Maina, & Ravizza, 1999; Castle, Deale, & Marks, 1995; Labad et al., 2008; Lensi et al., 1996), including Indian studies (Akhtar, Wig, Varma, Pershad, & Verma, 1978; Jaisoorya, Reddy, Srinath, & Thennarasu, 2009; Khanna & Mukherjee, 1992). It is possible that cultural factors have an influence on the phenotypic presentation of OCD with respect to gender. There is some data from India to suggest higher frequency of themes related to dirt and contamination and lower frequency of aggressive obsessions among Hindu patients (Akhtar et al.,

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Table 4 Relationship between symptom dimensions and clinical characteristics. Contamination rho p

Sex/religious rho p

Aggression rho p

Symmetry rho p

Somatic rho p

Collecting rho p

Miscellaneous rho p

0.02 0.77

 0.04 0.64

 0.13 0.09

 0.06 0.46

 0.14 0.08

 0.12 0.12

Age

0.11 0.16

 0.31nn o 0.001

 0.17n 0.03

0.01 0.90

Age of onset

0.11 0.16

 0.34nn o 0.001

 0.16n 0.04

0.16n 0.04

YBOCS-11 score

0.19n 0.02

 0.10 0.19

0.03 0.70

0.07 0.40

0.03 0.70

0.17n 0.03

 0.05 0.50

 0.03 0.71

0.06 0.47

0.08 0.31

0.11 0.18

0.08 0.34

 0.16 0.05

0.10 0.21

 0.08 0.32

 0.04 0.63

 0.14 0.08

 0.01 0.96

 0.01 0.99

CGI-S

0.28nn o 0.001

GAF

 0.16n 0.04

n

p o 0.05 - trend towards significance. p o 0.01 - significant.

nn

Table 5 Regression analyses showing association of symptom dimensions with common comorbid disorders. Comorbid disorder

Contamination B (SE) OR CI p

Sex/religion B (SE) OR CI p

Aggression B (SE) OR CI p

Symmetry B (SE) OR CI p

Somatic B (SE) OR CI p

Collecting B (SE) OR CI p

Miscellaneous B (SE) OR CI p

MDDa

0.01(0.05) 1.01 0.92–1.11 0.86

0.04(0.05) 1.04 0.95–1.14 0.39

 0.02(0.05) 0.98 0.89–1.07 0.63

0.07 (0.05) 1.07 0.96–1.18 0.22

 0.06(0.24) 0.94 0.59–1.5 0.79

 0.02(0.17) 0.98 0.7–1.37 0.91

0.05(0.05) 1.05 0.95–1.15 0.32

Dysthymia

 0.05(0.06) 0.95 0.85–1.06 0.37

0.05(0.06) 1.05 0.94–1.12 0.37

0.02(0.06) 1.02 0.9–1.15 0.76

 0.06(0.07) 0.94 0.82–1.29 0.41

0.06(0.19) 1.06 0.74–1.53 0.75

 0.01(0.24) 0.99 0.62–1.59 0.97

 0.01(0.06) 0.99 0.88–1.12 0.89

Social phobia

 0.01 (0.06) 0.99 0.88–1.13 0.97

0.01(0.06) 1.01 0.89–1.13 0.96

0.12(0.06) 1.13 1.01–1.26 o 0.05n

0.03(0.07) 1.03 0.9–1.18 0.64

 5.58(3671.9) 0.01 0.00 0.99

 0.06(0.22) 0.95 0.61–1.47 0.81

0.01(0.06) 1.01 0.9–1.14 0.85

GADb

 0.05 (0.08) 0.96 0.82–1.11 0.54

 0.03(0.08) 0.97 0.83–1.13 0.72

0.11(0.07) 1.11 0.96–1.29 0.15

0.14(0.09) 1.16 0.96–1.38 0.12

 0.06(0.27) 0.95 0.56–1.59 0.83

 0.08(0.31) 0.93 0.51–1.69 0.8

 0.14(0.12) 0.87 0.69–1.1 0.24

Panic disorder

 0.18 (0.11) 0.84 0.68–1.03 0.09

0.02(0.08) 1.02 0.87–1.2 0.80

0.12(0.08) 1.12 0.96–1.32 0.16

 0.02(0.11) 0.98 0.79–1.21 0.87

 4.85(3677.3) 0.01 0.00 0.99

 5.3(2678.7) 0.01 0.00 0.99

 0.06(0.09) 0.95 0.79–1.14 0.56

Any anxiety disorder

 0.06(0.05) 0.94 0.86–1.03 0.18

 0.01(0.05) 0.99 0.90–1.08 0.78

0.10(0.05) 1.11 1.02–1.21 0.02n

0.02(0.05) 1.02 0.92–1.13 0.74

 0.31(0.27) 0.74 0.43–1.26 0.26

 0.1(0.19) 0.9 0.63–1.3 0.58

 0.01(0.05) 0.99 0.9–1.1 0.85

AAPDc

 0.01(0.07) 0.99 0.87–1.13 0.88

0.01(0.06) 1.01 0.89–1.13 0.98

 0.04(0.07) 0.96 0.84–1.11 0.59

0.1(0.08) 1.11 0.96–1.28 0.18

 0.79(3759.3) 0.01 0.00 0.99

 0.29(0.31) 0.75 0.41–1.36 0.34

0.12(0.07) 1.12 0.98–1.28 0.09

OCPDd

0.07(0.06) 1.07 0.96–1.20 0.23

0.02(0.06) 1.02 0.91–1.14 0.74

 0.03(0.06) 0.97 0.86–1.1 0.63

0.06(0.06) 1.06 0.94–1.19 0.33

 5.87(3724.9) 0.01 0.00 0.99

0.11(0.16) 1.12 0.82–1.53 0.47

0.01(0.06) 1.01 0.89–1.14 0.89

p o 0.05 - significant. Major depressive disorder. Generalized anxiety disorder. c Anxious avoidant personality disorder. d Obsessive–compulsive personality disorder. n

a

b

1978; Khanna & Channabasavanna, 1988). However, studies on the phenomenology of OCD in Indian patients report that the symptom profile is similar to the Western population (Akhtar, Wig, Varma, Pershad, & Verma, 1975; Khanna & Channabasavanna, 1988;

Ravi Kishore, Samar, Janardhan Reddy, Chandrasekhar, & Thennarasu, 2004). In this study, OCD patients with poor insight had somewhat higher scores on contamination dimension. The finding is in

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accordance with that of a previous study of 545 patients from our center which reported a higher rate of contamination fears and washing compulsions in those with poor insight (Cherian et al., 2012). In that study, factor-analyzed contamination dimension predicted poorer insight and presence of forbidden thoughts (sexual, religious, aggressive) predicted better insight. We also found a marginal association between poor insight and hoarding which is consistent with past literature (Frost, Krause, & Steketee, 1996). We did not find any association between poor insight and the other dimensions although previous studies found poor insight in those with somatic obsessions (Frost et al., 1996). Our sample only had a small percentage of patients with somatic obsessions (2.5%) and that may be the reason for lack of association with poor insight. We found patients scoring high on contamination had greater severity of illness, as assessed by CGI and somewhat poorer functioning. This could be because patients scoring high on contamination spend more time involved in their symptom, therefore having greater impact on functioning. It is estimated that more than 50% of OCD patients have other psychiatric disorders (Pigott, L’Heureux, Dubbert, Bernstein, & Murphy, 1994). We found 57% of patients having one or more additional Axis I diagnosis, mostly mood and anxiety disorders. A family study employing latent class analysis identified a specific OCD subtypes are associated with major depression and generalized anxiety disorder, and a distinct subtype with panic disorder, agoraphobia, and tic disorder (Nestadt et al., 2003). In our study, aggression dimension was associated with presence of any anxiety disorder (all anxiety disorders taken as a whole rather than individually) and social phobia in particular. A recent study reported a broad association between anxiety disorders and depression and factor I (aggression/religion/sex/somatic/checking); panic disorder, agoraphobia and bipolar disorder and factor II (symmetry/ordering/repeating/counting); and Tourette syndrome and eating disorders with factor III (contamination and cleaning) (Hasler et al., 2005). Previous studies have also reported symmetry to be associated with bipolar disorders, panic, and substance use disorders (Hasler et al., 2005) and with tics and impulse control disorders like nail biting and trichotillomania (de Mathis et al., 2006). While our study found association between aggression dimension and presence of any anxiety disorder/social phobia, there was no specific association with any individual anxiety disorders. Lack of specific association with individual anxiety disorders could be due to low rates of anxiety disorders in our sample (Table 3). Similarly, a lack of associations between other symptom dimensions and comorbid disorders could be possibly because of low rate of some of the disorders in our sample. For example, in a large Brazilian study, tic-related OCD was associated with more severe scores on the aggressive, sexual/ religious and hoarding symptom dimensions of the DYBOCS in addition to its association with early onset, male preponderance, sensory phenomena, and comorbidity with anxiety and impulse control disorders and ADHD (de Alvarenga et al., 2012). Association between aggressive dimension and Tourette syndrome has also been reported in a study from Japan (Kano et al., 2012). Our study reports the clinical correlates associated with various symptom dimensions in a large sample of well characterized OCD subjects. The study demonstrates relatively specific associations between OCD symptom dimensions and other clinical features such as age at onset, gender, insight and comorbidity. Recent studies support that these dimensions may have unique neurobiological correlates. A study demonstrated an association between strategic planning and the DYBOCS hoarding dimension suggesting that OCD is a heterogeneous disorder with unique neuropsychological profile of hoarding dimension (Pinto et al., 2011). In a study of white matter abnormalities, symptom severity on the ‘obsessing’ dimension was negatively correlated with fractional anisotropy in

19

the corpus callosum and the cingulated bundle whereas severity on the ordering dimension was negatively correlated with the fractional anisotropy in the right inferior fronto-occipital fasciculus and the right optic radiation (Koch et al., 2012). Specific association between ordering and visual processing tracts suggests deficits in visual processing contributing perhaps to increased attention to irrelevant details. Association between obsession and certain tracts also suggest alterations in structures known to be relevant for cognitive control and inhibition. A recent study reported direct correlation between brain derived neurotrophic factor and severity of sexual/religious and aggressive dimensions on the DYBOCS (Dos Santos et al., 2012). The strengths of the study were the use of a dimensional scale, the D-YBOCS. Previous studies have used factors generated through factor analysis of Y–BOCS symptom checklist, to assess the influence on various clinical characteristics. This is a step forward to subtype this heterogeneous disorder into more homogenous subgroups. The study had a decent sample size. Consecutive sampling was done to minimize sampling bias and standard instruments were used to determine the diagnosis of OCD and assessment of severity. Our study sample consisted of patients suffering from moderate to severe illness which would have helped in better characterization of the phenotype. Our study has certain limitations, and the findings have to be interpreted in the light of some of these limitations. Cross sectional design of the study limits interpretation. Presence of OCD in first-degree relatives was determined by family history method and not by direct interview of the relatives. Family history method may not have been sensitive to diagnose OCD without prominent overt rituals. Therefore, we may have underestimated rates of OCD in first-degree relatives. Rates of certain co-morbid disorders were too low to establish any meaningful association with specific symptom dimensions. In many factor analytical studies religious, sexual, somatic and aggressive obsessions and checking are included in single dimension (Bloch et al, 2008), whereas the D-YBOCS has separate dimensions for aggression and somatic obsessions. To some extent, this may have limited comparisons across studies. Reliability exercises were not carried out and this remains a limitation although diagnoses and other associated clinical features were established by extensive clinical evaluation including confirmation by expert clinicians. Finally, we do not have data on response to treatment; the data on treatment response may have added to the knowledge on relative response or non-response of certain symptom dimensions to standard treatment modalities.

5. Conclusions That certain symptom dimensions are associated with unique clinical characteristics emphasizes the view that symptom dimensions could be employed to reduce the heterogeneity of OCD. There is growing evidence for a multidimensional view of OCD symptoms and these dimensions appear more homogenous than the macrophenotype (Mataix-Cols, 2006; Mataix-Cols et al., 2005) with possibly unique biological correlates (Gilbert et al., 2008; Hashimoto et al., 2011; van den Heuvel et al., 2009). Our study encourages further research to elucidate the neurobiological and genetic underpinnings of OCD symptom dimensions and supports inclusion of symptom dimensions in characterizing OCD in DSM-5 text (Leckman et al., 2010).

Acknowledgments Nil.

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