title: Cluster analysis of obsessive-compulsive spectrum disorders in patients with obsessive-compulsive disorder: clinical and genetic correlates.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, PO Box 19063, Tygerberg, 7505, Cape Town, South Africa. cl2@sun.ac.za
authors.forename: Christine
authors.initials: C
authors.lastname: Lochner
authors.forename: Sian M J
authors.initials: SM
authors.lastname: Hemmings
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Kinnear
authors.forename: Dana J H
authors.initials: DJ
authors.lastname: Niehaus
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Nel
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Corfield
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Moolman-Smook
authors.forename: Soraya
authors.initials: S
authors.lastname: Seedat
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Stein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016000:Cluster Analysis; D015897:Comorbidity; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005715:Gambling; D005838:Genotype; D006801:Humans; D007406:Interview, Psychological; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D016728:Self-Injurious Behavior / Q000453:epidemiology / Q000235:genetics; D012701:Serotonin / Q000235:genetics; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D005879:Tourette Syndrome / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D014256:Trichotillomania / Q000453:epidemiology / Q000235:genetics
chemical_list: D012701:Serotonin; D008995:Monoamine Oxidase