Pervasive developmental disorder and childhood-onset schizophrenia: comorbid disorder or a phenotypic variant of a very early onset illness?
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.
Sporn
Alexandra L
AL
Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
Addington
Anjené M
AM
Gogtay
Nitin
N
Ordoñez
Anna E
AE
Gornick
Michele
M
Clasen
Liv
L
Greenstein
Deanna
D
Tossell
Julia W
JW
Gochman
Peter
P
Lenane
Marge
M
Sharp
Wendy S
WS
Straub
Richard E
RE
Rapoport
Judith L
JL
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