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 1800 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 and not due to medication. A double-blind comparison of olanzapine and clozapine show superiority of clozapine for these medication on responders (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 onging genetic studies (100 TRIOS). Genetic data to date indicates significant association with four risk genes for schizophrenia, even with this limited sample size. Whole genomic screening studies show evidence for increased rate for small (50-100kb) rare copy number variants compared to healthy full siblings. These findings are being extended with a re-screening of all cases and their families with the illumina 1M SNP array.