This is an application for an NIMH Mentored Patient-Oriented Research Career Development Award (K23). The candidate's interest is in the early identification and treatment of schizophrenia. He has previously conducted research in the phenomenology and early clinical course of schizophrenia. This career development program will allow him to pursue 1) specialized training in the methods of early detection in schizophrenia, and 2) training in the procedures necessary to conduct genotype-phenotype association analyses. Training will include individual mentoring by experts in schizophrenia research and molecular genetics at the University of Iowa, as well as training at the laboratories of external consultants who are leading the research in schizophrenia prevention. The training program will also be closely integrated with a research plan focusing on the investigation of two candidate genes (brain-derived neurotrophic factor (BDNF) and Disrupted-in-Schizophrenia 1 (DISC1)) and their relationships with two quantitative phenotypes of schizophrenia (neurocognitive dysfunction and MRI brain volume deficits).
The aims of the research plan are 1) to identify neurocognitive and MRI brain morphometric correlates of BDNF and DISC1, and 2) to study neurocognitive dysfunction and structural brain deficits in unaffected siblings of schizophrenia probands. This integrated career development program, providing training in high-risk research methodology, molecular genetics, cognitive neuroscience and biostatistics, will enhance the candidate's ability to combine biological (e.g. endophenotypic traits, genetic variations) and clinical (e.g. prodromal symptoms, familial history) risk factors into multi-stage screening programs for the early identification of schizophrenia. Taken together, the training program and research plan provide the potential for scientific discovery as well as support for the establishment of an independent research career.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH068380-03
Application #
7261377
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Wynne, Debra K
Project Start
2005-09-01
Project End
2010-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
3
Fiscal Year
2007
Total Cost
$172,659
Indirect Cost
Name
University of Iowa
Department
Psychiatry
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Onwuameze, Obiora E; Titone, Debra; Ho, Beng-Choon (2016) Transitive inference deficits in unaffected biological relatives of schizophrenia patients. Schizophr Res 175:64-71
Rudd, Danielle S; Axelsen, Michael; Epping, Eric A et al. (2014) A genome-wide CNV analysis of schizophrenia reveals a potential role for a multiple-hit model. Am J Med Genet B Neuropsychiatr Genet 165B:619-26
Onwuameze, O E; Nam, K W; Epping, E A et al. (2013) MAPK14 and CNR1 gene variant interactions: effects on brain volume deficits in schizophrenia patients with marijuana misuse. Psychol Med 43:619-31
Wassink, Thomas H; Epping, Eric A; Rudd, Danielle et al. (2012) Influence of ZNF804a on brain structure volumes and symptom severity in individuals with schizophrenia. Arch Gen Psychiatry 69:885-92
Andreasen, Nancy C; Nopoulos, Peg; Magnotta, Vincent et al. (2011) Progressive brain change in schizophrenia: a prospective longitudinal study of first-episode schizophrenia. Biol Psychiatry 70:672-9
Brauns, Stefan; Gollub, Randy L; Roffman, Joshua L et al. (2011) DISC1 is associated with cortical thickness and neural efficiency. Neuroimage 57:1591-600
Capizzano, Aristides A; Toscano, Juana L Nicoll; Ho, Beng-Choon (2011) Magnetic resonance spectroscopy of limbic structures displays metabolite differences in young unaffected relatives of schizophrenia probands. Schizophr Res 131:4-10
Ho, Beng-Choon; Wassink, Thomas H; Ziebell, Steven et al. (2011) Cannabinoid receptor 1 gene polymorphisms and marijuana misuse interactions on white matter and cognitive deficits in schizophrenia. Schizophr Res 128:66-75
Ho, Beng-Choon; Andreasen, Nancy C; Ziebell, Steven et al. (2011) Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Arch Gen Psychiatry 68:128-37
Ho, Beng-Choon; Magnotta, Vincent (2010) Hippocampal volume deficits and shape deformities in young biological relatives of schizophrenia probands. Neuroimage 49:3385-93

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