Children and adolescents meeting DSM-IV criteria for schizophrenia are being obtained through vigorous national recruiting. Seventy-five 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 85 received the diagnosis of schizophrenia at 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 45x0 (Turners Syndrome). 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 is ongoing. 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. Pilot genetic data indicates significant association with several risk genes for schizophrenia, even with this limit sample size.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002581-13
Application #
6823822
Study Section
(CHP)
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
2003
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Rapoport, Judith; Chavez, Alex; Greenstein, Deanna et al. (2009) Autism spectrum disorders and childhood-onset schizophrenia: clinical and biological contributions to a relation revisited. J Am Acad Child Adolesc Psychiatry 48:10-8
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
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
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
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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