Defense Date
2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Pharmaceutical Sciences
First Advisor
Dr.Joseph McClay
Abstract
Schizophrenia (SCZ) is a devastating disorder, with its pathogenesis remaining poorly understood. Nevertheless, current research indicates that it emerges from the intricate interplay of numerous genetic and environmental risk factors. While antipsychotic drugs (APs) represent the primary form of treatment, no singular medication proves universally effective. Treatment failure rates remain high, and these pharmaceuticals are associated with severe and incapacitating side effects. Consequently, the primary objective of this doctoral dissertation is to employ genomic methodologies in enhancing comprehension and prediction of AP response. The overarching study is structured around three specific aims. The first two aims involve mechanistic studies in mice of genes previously associated with APs response in humans. More specifically, aim 1 involves elucidating the mechanistic role of the Anks1b gene in APs response through the use of knockout mice compared to wild-type mice treated with atypical AP medication olanzapine. Aim 2 focuses on examining the expression of Cntnap5a as a preclinical indicator of AP drug response in mouse cortex and hippocampus. Lastly, aim 3 entails conducting a genome-wide investigation of gene expression alterations in the mouse prefrontal cortex induced by chronic clozapine administration.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
7-22-2024
Included in
Laboratory and Basic Science Research Commons, Molecular and Cellular Neuroscience Commons, Molecular Genetics Commons, Pharmacy and Pharmaceutical Sciences Commons