Genetic Variation of the Mu Opioid Receptor (OPRM1) and Dopamine D2 Receptor (DRD2) is Related to Smoking Differences in Patients with Schizophrenia but not Bipolar Disorder

Hirasawa-Fujita, Mika; Bly, Michael J.; Ellingrod, Vicki L.; Dalack, Gregory W.; Domino, Edward F.

doi:10.3371/csrp.mhmb.061314

Cited by 13 publications

(3 citation statements)

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“…However, its role in developing ADRs to ARI is currently unknown. Opioid receptor activation inhibits GABAergic interneurons in order to increase dopamine release (Hirasawa-Fujita et al, 2017). Therefore, higher dopamine concentration in OPRM1 rs1799971 wild-type homozygotes may increase the risk of somnolence.…”

Section: Discussionmentioning

confidence: 99%

Safety and cardiovascular effects of multiple-dose administration of aripiprazole and olanzapine in a randomised clinical trial

Koller

Almenara

Mejía

et al. 2020

Preprint

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Objective: To assess adverse events and safety of aripiprazole and olanzapine treatment. Methods: Twenty-four healthy volunteers receiving 5 daily oral doses of 10 mg aripiprazole and 5 mg olanzapine in a crossover clinical trial were genotyped for 46 polymorphisms in 14 genes by qPCR. Drug plasma concentrations were measured by HPLC-MS/MS. Blood pressure and 12-lead ECG were measured in supine position. Adverse events were also recorded. Results: Aripiprazole decreased diastolic blood pressure on the first day and decreased QTc on the third and fifth day. Olanzapine had a systolic and diastolic blood pressure, heart rate and QTc lowering effect on the first day. Polymorphisms in ADRA2A, COMT, DRD3 and HTR2A genes were significantly associated to these changes. The most frequent adverse drug reactions to aripiprazole were somnolence, headache, insomnia, dizziness, restlessness, palpitations, akathisia and nausea while were somnolence, dizziness, asthenia, constipation, dry mouth, headache and nausea to olanzapine. Additionally, HTR2A, HTR2C, DRD2, DRD3, OPRM1, UGT1A1 and CYP1A2 polymorphisms had a role in the development of adverse drug reactions. Conclusions: Olanzapine induced more cardiovascular changes; however, more adverse drug reactions were registered to aripiprazole. In addition, some polymorphisms may explain the difference in the incidence of these effects among subjects.

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Section: Discussionmentioning

confidence: 99%

Safety and cardiovascular effects of multiple-dose administration of aripiprazole and olanzapine in a randomised clinical trial

Koller

Almenara

Mejía

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…However, its role in developing ADRs to ARI is currently unknown. Opioid receptor activation inhibits GABAergic interneurons in order to increase dopamine release (Hirasawa‐Fujita, Bly, Ellingrod, Dalack, & Domino, 2017). Therefore, higher dopamine concentration in OPRM1 rs1799971 wild‐type homozygotes may increase the risk of somnolence.…”

Section: Adverse Drug Reactionsmentioning

confidence: 99%

Safety and cardiovascular effects of multiple‐dose administration of aripiprazole and olanzapine in a randomised clinical trial

Koller

Almenara

Mejía

et al. 2020

Human Psychopharmacology

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ObjectiveTo assess adverse events (AEs) and safety of aripiprazole (ARI) and olanzapine (OLA) treatment.MethodsTwenty‐four healthy volunteers receiving five daily oral doses of 10 mg ARI and 5 mg OLA in a crossover clinical trial were genotyped for 46 polymorphisms in 14 genes by qPCR. Drug plasma concentrations were measured by high‐performance liquid chromatography tandem mass spectrometry. Blood pressure (BP) and 12‐lead electrocardiogram were measured in supine position. AEs were also recorded.ResultsARI decreased diastolic BP on the first day and decreased QTc on the third and fifth day. OLA had a systolic and diastolic BP, heart rate and QTc lowering effect on the first day. Polymorphisms in ADRA2A, COMT, DRD3 and HTR2A genes were significantly associated to these changes. The most frequent adverse drug reactions (ADRs) to ARI were somnolence, headache, insomnia, dizziness, restlessness, palpitations, akathisia and nausea while were somnolence, dizziness, asthenia, constipation, dry mouth, headache and nausea to OLA. Additionally, HTR2A, HTR2C, DRD2, DRD3, OPRM1, UGT1A1 and CYP1A2 polymorphisms had a role in the development of ADRs.ConclusionsOLA induced more cardiovascular changes; however, more ADRs were registered to ARI. In addition, some polymorphisms may explain the difference in the incidence of these effects among subjects.

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“…Furthermore, recent genetic studies have identified other genes associated with increased tobacco use in those with schizophrenia. These include the functional polymorphism Val66Met in the BDNF gene (Zhang 2012; Gurillo 2015) and functional polymorphisms in the dopamine β-hydroxylase gene DBH (Zhang 2012; Hirasawa-Fujita 2017), the μ-opioid receptor gene OPRM1 and the dopamine-2 receptor gene DRD2 (Hirasawa-Fujita 2017).…”

Section: Shared Genetic Vulnerability: a Second Alternative Hypothesismentioning

confidence: 99%

Tobacco smoking and schizophrenia: re-examining the evidence

Isuru

Rajasuriya

2019

BJPsych advances

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SUMMARYTobacco smoking among people with mental illnesses can be explained by biological, psychological and social factors. The prevalence of smoking in people diagnosed with schizophrenia is higher than in people with other mental disorders and in the general population. This article explores three current hypotheses that explain this higher prevalence of smoking in schizophrenia. The first, the self-medication hypothesis, is increasingly countered by a growing body of evidence indicating that smokers experience more severe symptoms of schizophrenia. Numerous researchers have already identified smoking as a possible risk factor for the development of schizophrenia, which is the second hypothesis. The third hypothesis (shared genetic vulnerability) identifies certain genes that confer vulnerability for both schizophrenia and nicotine dependence. Understanding the reasons behind the higher prevalence of smoking among people with schizophrenia is vital in planning effective primary, secondary and tertiary smoking prevention for these individuals.LEARNING OBJECTIVESAt the end of this article, readers will be able to: •understand the self-medication hypothesis in relation to tobacco smoking by people with schizophrenia•understand the role of tobacco smoking as a possible risk factor for causation of schizophrenia•understand the role of shared genetic vulnerability in the causation of both schizophrenia and nicotine dependence.

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Genetic Variation of the Mu Opioid Receptor (OPRM1) and Dopamine D2 Receptor (DRD2) is Related to Smoking Differences in Patients with Schizophrenia but not Bipolar Disorder

Cited by 13 publications

References 84 publications

Safety and cardiovascular effects of multiple-dose administration of aripiprazole and olanzapine in a randomised clinical trial

Safety and cardiovascular effects of multiple-dose administration of aripiprazole and olanzapine in a randomised clinical trial

Safety and cardiovascular effects of multiple‐dose administration of aripiprazole and olanzapine in a randomised clinical trial

Tobacco smoking and schizophrenia: re-examining the evidence

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