Genetic Testing For Mental Health Conditions – University of Alberta researcher Catherine Aitchison and her team are using DNA testing to predict response to prescription drugs.
While prescription drugs and antipsychotics have helped millions of people live happier, more productive lives, many don’t.
Genetic Testing For Mental Health Conditions
Catherine Aitchison, a researcher and professor of psychiatry and associate director of mental health at the Institute of Neuroscience and Mental Health at the University of Alberta, is part of a team studying how our genetic makeup affects our response to psychoactive drugs.
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“Just as our genes determine our hair and eye color, they can also determine how our bodies respond to drugs,” said Atchison, a member of the Women’s and Children’s Health Research Institute.
“Pharmaceuticals are the study of how a person’s unique genetic makeup affects their response to drugs. Our goal is to guide prescribing and help doctors choose the right drug and dose for each individual.”
Certain enzymes in the liver cause chemical changes in drugs. Sometimes chemical changes make drugs more or less active in the body. Even small differences in the genes for these liver enzymes can significantly affect the safety or effectiveness of a drug.
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Atchison’s group performed a robust genetic test for the four enzymes most commonly associated with psychoactive drugs. People with mutations in these enzymes may experience adverse drug reactions, but doctors can prescribe different medications if these mutations are detected.
His team is currently testing these genes in a trial of Albertans with treatment-resistant mood disorders.
“For most patients, taking an antioxidant means working with a doctor to choose a drug, then using a long trial and error process, and potentially serious side effects along the way. The first anti-oxidant has about a 50 percent chance of it working — not much better than a dime,” Atchison said.
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“If medication can be used before and after drug selection, we can help shorten the time to find effective drugs and medications.”
Randomized trials have shown that pharmacological testing is accurate and cost-effective. Comprehensive and reliable testing of a wide range of genes is necessary before public exposure. Physicians, pharmacists, and other health care professionals must be taught best practices and guidelines.
“For populations that previously had no genetic data, such as indigenous peoples, it was necessary to sequence the DNA,” Aitchison said. This is time consuming and expensive. “So we’re trying to develop more efficient DNA sequencing methods.” said.
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“Our long-term goal is to provide cost-effective testing through Alberta Health Services and leave no one behind.”
Funding for this research was provided by the Canada Innovation Foundation, Institute of Neuroscience and Mental Health, University of Alberta Faculty of Medicine and Dentistry, Office of the Provost and Office of the Vice-President (Academic), Alberta Innovation Corporation. ) provided by the University of Alberta and Munnar University. Alberta Undergraduate Research Program, Natural Sciences and Engineering Research Council of Canada, Government of Alberta and European Commission. In psychiatry, the selection of antipsychotics and antidepressants is often based on trial and error. The prescription of these drugs is complicated by poor efficacy and adverse drug reactions (ADR). These lead to poor compatibility. Pharmacology (PGx) looks at how genetic variation affects an individual’s response to drugs. Pharmacology testing is a tool that can help clinicians select psychotropic medications as part of a more personalized prescribing approach. This may improve the use and compliance of these medications. Yet the implementation of PGx in UK mental health settings has been slow. This review aims to identify barriers and facilitators to the implementation of PGx in psychiatric wards and to determine how these apply to uptake of PGx by NHS mental health providers. A systematic search strategy was developed and PsychInfo, EmBase, and PubMed databases were searched to retrieve 11 eligible articles. Common barriers to implementing PGx include cost, concerns about integration into current workflows, and lack of understanding of PGx; However, general drivers include optimism that PGx will lead to precise dosing, reduce adverse effects, and become a promising clinical treatment option for psychiatric disorders. general section. NHS psychiatric settings should consider and overcome these barriers to the uptake of PGx, whilst taking advantage of the enablers identified in this review.
Prior to the COVID-19 outbreak, the annual social and economic cost of mental health disorders in the UK was estimated at £119 billion (Oshe and Bell, 2020). Mental health (MH) disorders are a major cause of global health burden (Vos et al., 2015). Medications can treat mental illness; Antioxidants and antipsychotics are often prescribed. However, in some patients, the benefits of such drug interventions are hampered by treatment response and significant adverse drug reactions (ADRs) (Senior et al., 2010; Huchen et al., 2010). Approximately 30% of patients with schizophrenia are treatment-resistant, and similarly, 50% of patients on antidepressants are initially unresponsive (Meltzer, 1997; Fava, 2003; Lally et al., 2016). It is estimated that 40% of people taking antidepressants experience side effects (Bull et al., 2002). Antipsychotic medications can cause a variety of adverse effects (Huhn et al., 2019). Limited efficacy and adverse effects, coupled with the relapsing-remitting nature of many psychiatric disorders, may lead to inappropriate use of this drug class (Semahegn et al., 2020). Furthermore, medication nonadherence is a predictor of poor health and risk of relapse in a cohort of MH patients (Leucht et al., 2012; Kato et al., 2021).
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Research on how genetic variation affects drug response (Roden, 2006). These mutations are usually single-nucleotide polymorphisms (SNPs), where a single base in a gene is replaced, resulting in a different genetic sequence (Butler, 2012). Previous studies have shown that over 90% of the population has at least one mutation that alters drug response (Van Drest et al. 2014; Bush et al. 2019). PGx has great potential for impact in the field of psychiatry. Prescriptions of antipsychotics to the NHS have increased in recent years (Wilson, 2020). Approximately 10% of adults in the UK take an antioxidant (Taylor et al., 2019). During the COVID-19 pandemic, there was a 4 million increase in NHS prescriptions for antidepressants and a £140 million increase in spending compared to the previous year (Rabia et al. 2021). Antipsychotics are the mainstay of treatment for schizophrenia. The selection of these drugs is often determined by trial and error. Implementation of PGx in psychiatry has the potential to improve this by shifting current practice to a more personalized approach to prescribing, taking into account patients’ genetic characteristics. This is expected to improve efficacy and reduce adverse drug reactions (ADRs) associated with antipsychotics (Manchia et al., 2020).
Pharmacological agents affect drug response, i.e. alter the pharmacokinetics or dynamics of the drug (Roden, 2006). Until now, the focus of psychiatric PGx has been on drug development. The cytochrome P450 family is well studied (Bosman et al., 2021). 2018). In psychiatric PGx, the genes encoding the CYP2D6 and CYP2C19 isozymes have been most extensively studied (van Westrenen et al. It is estimated that 36% and 62% of people worldwide have enzyme variants affecting the function of these two enzymes, respectively (Koopmans et al. , 2021). Most psychotropic drugs are metabolized by these enzymes; genetic variation of these enzymes can affect the pharmacokinetics of psychotropic drugs (Hiemke et al., 2018). If the active compound is cleared too rapidly, or if the clearance of the drug from plasma is reduced, the risk of ADR may increase. To date, the evidence base for gene-based dynamics of pharmacodynamics is limited.Genetic interactions with common antipsychotics are shown in Figure 1.
Figure 1. Adapted from Bosman C. et al. . CYP2D6 and CYP2C19 are common metabolic pathways for a number of antioxidants and antipsychotics. Of note is the well-documented drug-drug interaction between HLA-B and phenytoin/carbazamepine.
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Drug-gene interactions that lead to genetic changes in the drug-drug gene (Peters et al., 2021)). Basic knowledge of pharmacology
The database provides information related to DGI, such as the evidence base supporting DGI and recommended actions for implementation. Recommendations are graded by strength of evidence. There are currently several types of drug use tests, but only a limited number are related to mental illness. Busman
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