Childhood Onset Schizophrenia

National Institute Of Mental Health

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Abstract

Children and adolescents meeting DSM-IV criteria for schizophrenia are being obtained through vigorous national recruiting. Ninety subjects and their families have participated to date in this study of the phenomenology, neurobiology and pharmacologic response of childhood onset schizophrenia. Over 1400 medical records have been reviewed from which 250 patients and their families appearing to meet DSM-IV criteria for schizophrenia with onset of psychosis prior to age 12 were screened in person. A total of 95 received the diagnosis of schizophrenia at NIMH screening. A large number of children are receiving the diagnosis of schizophrenia inappropriately resulting in inappropriate treatment, even at academic centers. Our findings to date indicate continuity between childhood onset and later onset schizophrenia, with evidence that childhood onset schizophrenia may result from a more severe neurodevelopment lesion. Family/genetic data indicate three cases (5%) have familial schizophrenia, not higher than seen with adult cases; one subject had a 1:7 balanced chromosomal translocation; four subjects had a microdeletion at 22q11; one had uniparental isodisomy at 5q; two had 45x0 (Turners Syndrome); one had trisomy X. Three of 45 full siblings are mentally retarded with two meeting criteria for autism. Probands show greater premorbid developmental delay particularly for language, than seen for the later onset disorder. Autonomic and eye tracking measures parallel these of adult schizophrenia. Brain MRI abnormalities resemble those of adult onset schizophrenia and with more striking and consistent progression with age. This progressive loss appears specific to schizophrenia. A double-blind comparison of olanzapine and clozapine suggests supenarity of clozapine 4, 5, 6, 10). Several lines of evidence indicate greater genetic loading for these cases and our national case finding is being expanded to obtain 120 probands for future genetic studies. Genetic data to date indicates significant association with four risk genes for schizophrenia, even with this limited sample size. Genomic screening studies are underway to test more subtle evidence of genomic instability.