Ethical Issues of Genetic Testing in Schizophrenia
Ethical Issues of Genetic Testing in Schizophrenia
Pharmacogenetics is the field where genetic variation can be used to predict response to medication and likelihood of side-effects to medications. The genetic pathways of neurotransmitters (dopamine, serotonin and glutamine) have been examined as targets for drug actions, as well as metabolic pathways of the drugs themselves (i.e. cytochrome P2D6 or catecholamine methyl transferase).
Although clozapine is the mainstay treatment for patients who do not respond to other neuroleptics, not all patients are responders, and others have debilitating side-effects necessitating the termination of treatment. It would be helpful to have measures to be able to predict the likelihood of treatment response or of accruing side-effects. To date, there have been several studies and meta-analyses that have attempted to find an association of response to clozapine and also risk of its side-effects with variants of several genes, such as all the dopamine receptor D receptor and some 5HT receptor genes. Yet, none have been consistently replicated in large enough populations of uniformly treated patients. Thus, currently, there is no DNA screening measure that would be appropriate for use in the clinic.
Tardive dyskinesia, a severe side-effect of the first-generation antipsychotic medications, has been found to be associated with a Ser9Gly polymorphism in the dopamine D3 receptor gene and, in another study, with the SLC18A2 vesicular monoamine transporter gene. Again, numbers of participants are small in these studies and validity is not yet refined enough for translation into the clinic.
Weight gain and the metabolic syndrome are the most prevalent side-effects of the newer second-generation antipsychotic medications. The 5HT2C receptor gene has been associated with this side-effect in several studies, but this too is not yet a finding ready for clinical use.
Use of Genetic Testing for Personalized Medicine (Pharmacogenetics)
Pharmacogenetics is the field where genetic variation can be used to predict response to medication and likelihood of side-effects to medications. The genetic pathways of neurotransmitters (dopamine, serotonin and glutamine) have been examined as targets for drug actions, as well as metabolic pathways of the drugs themselves (i.e. cytochrome P2D6 or catecholamine methyl transferase).
Response to Clozapine
Although clozapine is the mainstay treatment for patients who do not respond to other neuroleptics, not all patients are responders, and others have debilitating side-effects necessitating the termination of treatment. It would be helpful to have measures to be able to predict the likelihood of treatment response or of accruing side-effects. To date, there have been several studies and meta-analyses that have attempted to find an association of response to clozapine and also risk of its side-effects with variants of several genes, such as all the dopamine receptor D receptor and some 5HT receptor genes. Yet, none have been consistently replicated in large enough populations of uniformly treated patients. Thus, currently, there is no DNA screening measure that would be appropriate for use in the clinic.
Tardive dyskinesia, a severe side-effect of the first-generation antipsychotic medications, has been found to be associated with a Ser9Gly polymorphism in the dopamine D3 receptor gene and, in another study, with the SLC18A2 vesicular monoamine transporter gene. Again, numbers of participants are small in these studies and validity is not yet refined enough for translation into the clinic.
Weight gain and the metabolic syndrome are the most prevalent side-effects of the newer second-generation antipsychotic medications. The 5HT2C receptor gene has been associated with this side-effect in several studies, but this too is not yet a finding ready for clinical use.
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