title: Pervasive developmental disorder and childhood-onset schizophrenia: comorbid disorder or a phenotypic variant of a very early onset illness?
abstract: BACKGROUND
  Childhood-onset schizophrenia (COS) is a severe form of the adult-onset disorder with a high rate of premorbid developmental abnormalities. Early symptoms of pervasive developmental disorder (PDD) have been reported in five independent studies of COS. In this study, we compared evidence for premorbid PDD as a nonspecific manifestation of impaired neurodevelopment seen in schizophrenia, or as an independent risk factor for COS.
  
  
  METHODS
  Diagnosis of past or current autism or PDD was made according to the DSM-IV criteria. COS patients with and without PDD were compared with respect to neuropsychological, clinical, and neurobiological measures. Several candidate genes for autism were examined in the entire COS sample and the subgroup with PDD using the Transmission Disequilibrium Test (TDT) and Quantitative TDT (QTDT).
  
  
  RESULTS
  Nineteen (25%) of COS probands had a lifetime diagnosis of PDD: one met criteria for autism, two for Asperger's disorder, and 16 for PDD not otherwise specified. Premorbid social impairment was most common feature for COS-PDD subjects. The PDD group did not differ from the rest of the COS sample with respect to age of onset, IQ, response to medications, and rate of familial schizotypy. Unexpectedly, two siblings of COS-PDD probands met criteria for nuclear autism. There was no difference between PDD and non-PDD groups with respect to initial brain magnetic resonance imaging (MRI) measures. However, rate of gray matter loss was greater for PDD (n = 12) than for the non-PDD (n = 27) subgroup (-19.5 +/- 11.3 mL/year vs. -9.6 +/- 15.3 mL/year; p =.05). None of eight candidate genes for autism were associated with COS or COS-PDD.
  
  
  CONCLUSIONS
  Premorbid PDD in COS is more likely to be a nonspecific marker of severe early abnormal neurodevelopment. However, the occurrence of two siblings of COS-PDD probands (17%) with nuclear autism remains to be understood.
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Sporn
authors.forename: Anjené M
authors.initials: AM
authors.lastname: Addington
authors.forename: Nitin
authors.initials: N
authors.lastname: Gogtay
authors.forename: Anna E
authors.initials: AE
authors.lastname: Ordoñez
authors.forename: Michele
authors.initials: M
authors.lastname: Gornick
authors.forename: Liv
authors.initials: L
authors.lastname: Clasen
authors.forename: Deanna
authors.initials: D
authors.lastname: Greenstein
authors.forename: Julia W
authors.initials: JW
authors.lastname: Tossell
authors.forename: Peter
authors.initials: P
authors.lastname: Gochman
authors.forename: Marge
authors.initials: M
authors.lastname: Lenane
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Sharp
authors.forename: Richard E
authors.initials: RE
authors.lastname: Straub
authors.forename: Judith L
authors.initials: JL
authors.lastname: Rapoport
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000704:Analysis of Variance; D001321:Autistic Disorder / Q000175:diagnosis; D001921:Brain / Q000473:pathology; D016009:Chi-Square Distribution; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis*; D015897:Comorbidity; D003710:Demography; D003937:Diagnosis, Differential; D005190:Family; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009483:Neuropsychological Tests; D010552:Personality Assessment; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D012561:Schizophrenia, Childhood / Q000175:diagnosis*; D012720:Severity of Illness Index