title: Paternal age related schizophrenia (PARS): Latent subgroups detected by k-means clustering analysis.
abstract: BACKGROUND
  Paternal age related schizophrenia (PARS) has been proposed as a subgroup of schizophrenia with distinct etiology, pathophysiology and symptoms. This study uses a k-means clustering analysis approach to generate hypotheses about differences between PARS and other cases of schizophrenia.
  
  
  METHODS
  We studied PARS (operationally defined as not having any family history of schizophrenia among first and second-degree relatives and fathers' age at birth ≥ 35 years) in a series of schizophrenia cases recruited from a research unit. Data were available on demographic variables, symptoms (Positive and Negative Syndrome Scale; PANSS), cognitive tests (Wechsler Adult Intelligence Scale-Revised; WAIS-R) and olfaction (University of Pennsylvania Smell Identification Test; UPSIT). We conducted a series of k-means clustering analyses to identify clusters of cases containing high concentrations of PARS.
  
  
  RESULTS
  Two analyses generated clusters with high concentrations of PARS cases. The first analysis (N=136; PARS=34) revealed a cluster containing 83% PARS cases, in which the patients showed a significant discrepancy between verbal and performance intelligence. The mean paternal and maternal ages were 41 and 33, respectively. The second analysis (N=123; PARS=30) revealed a cluster containing 71% PARS cases, of which 93% were females; the mean age of onset of psychosis, at 17.2, was significantly early.
  
  
  CONCLUSIONS
  These results strengthen the evidence that PARS cases differ from other patients with schizophrenia. Hypothesis-generating findings suggest that features of PARS may include a discrepancy between verbal and performance intelligence, and in females, an early age of onset. These findings provide a rationale for separating these phenotypes from others in future clinical, genetic and pathophysiologic studies of schizophrenia and in considering responses to treatment.
authors.affiliation: Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Hyejoo
authors.initials: H
authors.lastname: Lee
authors.forename: Dolores
authors.initials: D
authors.lastname: Malaspina
authors.forename: Hongshik
authors.initials: H
authors.lastname: Ahn
authors.forename: Mary
authors.initials: M
authors.lastname: Perrin
authors.forename: Mark G
authors.initials: MG
authors.lastname: Opler
authors.forename: Karine
authors.initials: K
authors.lastname: Kleinhaus
authors.forename: Susan
authors.initials: S
authors.lastname: Harlap
authors.forename: Raymond
authors.initials: R
authors.lastname: Goetz
authors.forename: Daniel
authors.initials: D
authors.lastname: Antonius
mesh_terms: D000328:Adult; D017668:Age of Onset; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D000857:Olfaction Disorders / Q000175:diagnosis / Q000209:etiology; D010331:Paternal Age; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D012307:Risk Factors; D012559:Schizophrenia / Q000145:classification / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D012565:Schizophrenic Psychology