Austin-Zimmerman, Isabelle;
(2022)
Pharmacogenetics of psychotropic drugs and genetic influences on adverse drug reactions.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
In this thesis, I investigate the impact of genetic variation on adverse drug reactions to psychotropic medications, with a focus on the metabolic and sleep related side effects of psychotropic drugs. In addition to reviewing published literature, I have considered this research topic in three main ways. Chapter one is a systematic review and meta-analysis of the impact of CYP2D6 genetic variation on antipsychotic-induced hyperprolactinaemia and weight gain, which are a relatively common but understudied adverse-drug reactions. Chapters two, three and four are based on data from UK Biobank, where I have conducted a hypothesis-driven analyses of known pharmacogenes and their association with two common adverse drug reactions: increased diabetes risk and sleep disturbance. In working on this thesis, two key limitations became apparent. Firstly, inconsistencies in genotyping and phenotyping make some findings difficult to interpret. Secondly, the nature of my analysis using cross-sectional UK Biobank data makes it difficult to draw firm conclusions on the causal direction of any observations. Chapter five aim to address these limitations. Here, I describe the set-up of a clinical study to assess pharmacogenetic interventions in a psychiatric patient population. Although only pilot data is available, due to a pause in recruitment during the Covid-19 pandemic, I describe the scientific rationale for the study and outline the work conducted to set-up and gain ethical approvals for the study. In addition, I outline my contribution to drafting clinical guidelines for the implementation of pharmacogenetic testing in the NHS.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Pharmacogenetics of psychotropic drugs and genetic influences on adverse drug reactions |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author's request. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10146577 |
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