GENETICS OF BRAIN STRUCTURE AND FUNCTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There is limited data regarding the molecular basis for alterations in brain size, shape or function in schizophrenia. One gene, brain derived neurotrophic factor (BDNF), is a secreted protein that is widely expressed in the hippocampus. BDNF has been found to play a role in hippocampal morphology and associated cognitive functions such as memory. To date, few studies have examined the relationship between BDNF polymorphism and hippocampal morphology. Moreover, prior neuroimaging studies have not distinguished between the anterior and posterior hippocampus, a critical distinction given previous data suggesting that structural and functional deficits may be most robust in the anterior hippocampus in schizophrenia. In this study, we propose assessing the relationship between magnetic resonance (MR) imaging measures of brain structure/function and genetic information in 100 healthy volunteers and 100 patients with schizophrenia. We will test the hypothesis that BDNF genetic variation is associated with anterior hippocampal structure and function and abnormalities in regions to which the anterior hippocampus is connected. These data may lead to novel endophenotypes in molecular genetic studies of schizophrenia as well as a better understanding of how genes contribute to brain development in healthy individuals.