This application for a Mentored Patient-Oriented Career Development Award (K23) is from a board-certified child and adolescent psychiatrist. He is proposing a research career development plan that will enable him to investigate late postnatal changes in the brain and their relationship to early-onset schizophrenia (EOS) (onset of psychotic symptoms by age 16) using neuroimaging technology. The applicant has preliminary data (Kumra et al, 2000) demonstrating a pattern of structural brain abnormalities in adolescents with EOS (e.g., subtle reduction in total cerebral volume largely accounted for by a reduction in gray matter, enlarged lateral ventricles) similar to those reported in adult patients with unspecified age at onset of schizophrenia. The applicant proposes to learn how to conduct additional neuroimaging studies examining white matter tract integrity in adolescents with EOS as inferred from diffusion tensor neuroimaging (DTI). DTI is a magnetic resonance imaging technique suited to the study of white matter because it can be used to quantify the magnitude and directionality of tissue water mobility in three dimensions. DTI provides a new method for estimating myelination in vivo. This technique may supply information about delays in brain ontogeny which may contribute to the vulnerability for an early onset of schizophrenia. The training plan will increase the applicant?s knowledge of methodological issues regarding structural imaging, DTI and comprehensive neuropsychological assessment methods. The training goals will be accomplished through the completion of the research plan. The research plan will provide the candidate with an opportunity to independently design, conduct, and complete a neuroimaging study in its entirety under the supervision of a group of experienced mentors. The training experiences in this award will provide the applicant with the necessary skills and experiences to independently undertake neuroimaging studies in the future and effectively compete for grant support.
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