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Genetics and psychotropic drugs: present and future clinical applications

Published on April 27, 2021   25 min

A selection of talks on Neuroscience

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0:00
Hello. My name is Chiara Fabbri. I'm a psychiatrist, and I work as a Marie Curie Research Fellow at the Institute of Psychiatry, Psychology and Neuroscience, King's College London. During this presentation, part of the Henry Stewart Talks series on pharmacogenetics, I will walk you through the main concepts of psychiatric pharmacogenetics, which is the study of how genetic variants influence the way we respond or have side effects to psychiatric medications.
0:31
This is the table of contents of topics that I will discuss. I want to start with a very simple question. Why is genetics relevant to psychopharmacotherapy?
0:43
Each pair of individuals is estimated to differ in about five million variants in their genomes. This includes single nucleotide polymorphisms or SNPs, that are substitutions of a single DNA base pair, and copy number variations, which consists of the insertions and deletions. These differences are responsible for inter-individual variability in the way the proteins in our cells are built and function, either directly or through the changes in the activity of regulatory elements. As a result, there are differences in the way different individuals respond to internal stimuli, such as hormones or neurotransmitters, and to external stimuli such as drugs.
1:28
There are three main methodological approaches to the study of how genetic variants influence the response to drugs. The first one to be developed was a candidate gene approach, that apply selective genotyping of variants in genes which are involved in drug metabolism or pharmacokinetics, or drug mechanism of action, or pharmacodynamics. This method is limited by our previous knowledge. Thus, in the last 10 years, Genome-Wide Association Studies, or GWAS, became the most common approach. In GWAS, hundred of thousands or millions of common variants have been genotyped across the genome thanks to a cost-effective technology called a microarray. The genotyped variants are spread across the genome and they cover the known common genetic variation in humans, in order to include all these variants in GWAS, without a priori hypothesis. Common variants are usually defined as those having a frequency of at least one percent in the population. In the last few years, next-generation sequencing has become more feasible in terms of cost, and it provides the possibility to explore the role of rare and unknown variance in coding regions, namely axons, or the complete genomic sequence.
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Genetics and psychotropic drugs: present and future clinical applications

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