Elsevier

Comprehensive Psychiatry

Volume 46, Issue 1, January–February 2005, Pages 14-19
Comprehensive Psychiatry

Cluster analysis of obsessive-compulsive spectrum disorders in patients with obsessive-compulsive disorder: clinical and genetic correlates

https://doi.org/10.1016/j.comppsych.2004.07.020Get rights and content

Abstract

Background

Comorbidity of certain obsessive-compulsive spectrum disorders (OCSDs; such as Tourette's disorder) in obsessive-compulsive disorder (OCD) may serve to define important OCD subtypes characterized by differing phenomenology and neurobiological mechanisms. Comorbidity of the putative OCSDs in OCD has, however, not often been systematically investigated.

Methods

The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I Disorders-Patient Version as well as a Structured Clinical Interview for Putative OCSDs (SCID-OCSD) were administered to 210 adult patients with OCD (N = 210, 102 men and 108 women; mean age, 35.7 ± 13.3). A subset of Caucasian subjects (with OCD, n = 171; control subjects, n = 168), including subjects from the genetically homogeneous Afrikaner population (with OCD, n = 77; control subjects, n = 144), was genotyped for polymorphisms in genes involved in monoamine function. Because the items of the SCID-OCSD are binary (present/absent), a cluster analysis (Ward's method) using the items of SCID-OCSD was conducted. The association of identified clusters with demographic variables (age, gender), clinical variables (age of onset, obsessive-compulsive symptom severity and dimensions, level of insight, temperament/character, treatment response), and monoaminergic genotypes was examined.

Results

Cluster analysis of the OCSDs in our sample of patients with OCD identified 3 separate clusters at a 1.1 linkage distance level. The 3 clusters were named as follows: (1) “reward deficiency” (including trichotillomania, Tourette's disorder, pathological gambling, and hypersexual disorder), (2) “impulsivity” (including compulsive shopping, kleptomania, eating disorders, self-injury, and intermittent explosive disorder), and (3) “somatic” (including body dysmorphic disorder and hypochondriasis). Several significant associations were found between cluster scores and other variables; for example, cluster I scores were associated with earlier age of onset of OCD and the presence of tics, cluster II scores were associated with female gender and childhood emotional abuse, and cluster III scores were associated with less insight and with somatic obsessions and compulsions. However, none of these clusters were associated with any particular genetic variant.

Conclusion

Analysis of comorbid OCSDs in OCD suggested that these lie on a number of different dimensions. These dimensions are partially consistent with previous theoretical approaches taken toward classifying OCD spectrum disorders. The lack of genetic validation of these clusters in the present study may indicate the involvement of other, as yet untested, genes. Further genetic and cluster analyses of comorbid OCSDs in OCD may ultimately contribute to a better delineation of OCD endophenotypes.

Introduction

There is growing recognition that obsessive-compulsive disorder (OCD) is a heterogeneous disorder, with clinical subtypes that are characterized by differing pathophysiological mechanisms and treatment outcomes [1], [2]. In clinical practice, for example, only about 40% to 60% of patients respond to the first trial of any particular selective serotonin reuptake inhibitor (SSRI) [3]. Other neurotransmitter mechanisms may also be involved in OCD; dysregulation of the dopaminergic system, in particular, has been postulated as a crucial factor in treatment-resistant OCD [4], [5]. Interestingly, the dopaminergic system may also be sensitized by repeated stress exposure [6], [7]. Furthermore, it has been suggested that patients with OCD who have particular variants of genes of the dopamine system are more likely to have tics [5], [8], and the presence of tics predicts worse response to SSRIs [8], [9]. A better understanding of subtypes of OCD might ultimately lead to new and more effective treatments [2].

One approach to subtyping OCD may be to consider issues of comorbidity. For instance, in their attempt to characterize psychopathological classes of disorders related to OCD to distinguish more homogeneous phenotypes with distinct etiologies, Nestadt et al [10] suggested that the OCD phenotype is expressed in 2 different subgroups on the basis of the presence of additional clinical syndromes that frequently accompany the condition. Moreover, OCD is commonly comorbid with obsessive-compulsive spectrum disorders (OCSDs; ie, conditions that share phenomenological and neurobiological features with OCD). For example, patients with comorbid OCD and Tourette's disorder (TD) appear to be characterized by specific demographic features (they are more likely to be male) and clinical characteristics (they are less likely to respond to SSRIs) [9]. While most patients with OCD suffer from at least one comorbid OCD spectrum disorder [11], there has been relatively little systematic investigation of the structure and implications of such comorbidity. It is possible, however, that different dimensions of OCD spectrum comorbidity in OCD correspond to differential involvement of various neurochemical systems and neuroanatomical circuits [12].

In this study, we aimed to delineate the hypothesized spectrum of OCD-related disorders in OCD using cluster analysis. The association of identified clusters with demographic variables (age, gender), clinical variables (age of onset, obsessive-compulsive [OC] symptom severity and dimensions, level of insight, temperament/character, treatment response), and monoaminergic genotypes was examined.

Section snippets

Subjects

Two hundred and ten adult patients with OCD (N = 210, 102 men and 108 women), with ages ranging between 18 and 75 years (35.7 ± 13.3), took part in the study. To be eligible, patients had to meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) [13] criteria for a primary diagnosis of OCD on the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I Disorders–Patient Version (SCID-II/P) [14] and had to

Cluster analysis

At the 1.1 linkage distance level, the following 3 clusters were obtained (Fig. 1):

  • (1)

    Cluster I, subsequently named “reward deficiency,” included TTM, pathological gambling, hypersexual disorder, and TD.

  • (2)

    Cluster II, subsequently named “impulsivity,” included compulsive shopping, kleptomania, eating disorders (including anorexia and bulimia nervosa), self-injury, and IED.

  • (3)

    Cluster III, subsequently named “somatic,” included BDD and hypochondriasis.

Comparison data

The following significant results were found:

  • (1)

    Cluster I

Discussion

Cluster analysis of the OCSDs in our sample of patients with OCD identified 3 separate clusters at the 1.1 linkage distance level. We labeled these clusters as (1) “reward deficiency” (including TTM, pathological gambling, hypersexual disorder, and TD), (2) “impulsivity” (including compulsive shopping, kleptomania, eating disorders, self-injury, and IED), and (3) “somatic” (including BDD and hypochondriasis).

A substantial literature has documented the comorbidity between OCD and TD, and the

Acknowledgments

This work was supported by the Medical Research Council of South Africa, the National Research Fund, and by a grant from the Obsessive-Compulsive Foundation. The help of the Obsessive-Compulsive Association of South Africa is gratefully acknowledged.

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