Genetic mechanisms of atypical antipsychotic drug response

Author

Rabha Mousa YounisFollow

DOI

https://doi.org/10.25772/X2XQ-JT53

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