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.
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| Bakalar, Jennifer L; Greenstein, Deanna K; Clasen, Liv et al. (2009) General absence of abnormal cortical asymmetry in childhood-onset schizophrenia: a longitudinal study. Schizophr Res 115:12-6 |
| Rapoport, Judith L; Gogtay, Nitin (2008) Brain neuroplasticity in healthy, hyperactive and psychotic children: insights from neuroimaging. Neuropsychopharmacology 33:181-97 |
| Walsh, Tom; McClellan, Jon M; McCarthy, Shane E et al. (2008) Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320:539-43 |
| Giedd, Jay N; Lenroot, Rhoshel K; Shaw, Philip et al. (2008) Trajectories of anatomic brain development as a phenotype. Novartis Found Symp 289:101-12;discussion 112-8, 193-5 |
| Arango, Celso; Moreno, Carmen; Martinez, Salvador et al. (2008) Longitudinal brain changes in early-onset psychosis. Schizophr Bull 34:341-53 |
| Shaw, Philip; Kabani, Noor J; Lerch, Jason P et al. (2008) Neurodevelopmental trajectories of the human cerebral cortex. J Neurosci 28:3586-94 |
| Gogtay, Nitin; Rapoport, Judith (2008) Clozapine use in children and adolescents. Expert Opin Pharmacother 9:459-65 |
| Gogtay, Nitin (2008) Cortical brain development in schizophrenia: insights from neuroimaging studies in childhood-onset schizophrenia. Schizophr Bull 34:30-6 |
| Lenroot, Rhoshel K; Gogtay, Nitin; Greenstein, Deanna K et al. (2007) Sexual dimorphism of brain developmental trajectories during childhood and adolescence. Neuroimage 36:1065-73 |
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