Polymorphic Expression of Cyp2C19 and Cyp2D6 in the Developing and Adult Human Brain Causing Variability in Cognition, Risk for Depression and Suicide: The Search for the Endogenous Substrates

Ingelman‐Sundberg, Magnus; Persson, Anna; Jukić, Marin M.

doi:10.2217/pgs.14.151

Cited by 29 publications

(29 citation statements)

References 23 publications

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“…CYP2D6, on the other hand, is also expressed in neurons, in many brain structures, where it catalyzes the formation of dopamine and serotonin from tyramine and 5‐hydroxytryptamin, respectively, and is involved in the metabolism of many neurosteroids (Anna Haduch, Bromek, & Daniel, ; Wang, Li, Dong, & Yue, ). In the past, CYP2D6 LOF alleles have been associated with personality traits in healthy volunteers (Penas, Dorado, Pacheco, Gonzalez, & LLerena, ) and CYP2D6 gene duplications with suicidality (Ingelman‐Sundberg, Persson, & Jukic, ). Incidentally, the ABCB1 rs2032582 polymorphism has been associated with suicide attempts as well, (Blazquez et al, ; Boiso Moreno et al, ) further supporting a functional interaction between the two genes.…”

Section: Discussionmentioning

confidence: 99%

ABCB1 and CYP2D6 polymorphisms and treatment response of psychotic patients in a naturalistic setting

Papazisis

Goulas

Sarrigiannidis

et al. 2017

Human Psychopharmacology

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Objectives: The aim of our study was to examine the association between ABCB1 polymorphisms G2677T/A (rs2032582) and C3435T (rs1045642) and common CYP2D6 variants, with the response to antipsychotic treatment of psychotic patients, in a naturalistic setting, in Greece.Methods: One hundred patients suffering from schizophrenia and other psychotic disorders were included in the study. Dosages were normalized to chlorpromazine equivalents. Response following 1 month of treatment was assessed as either a continuous variable, using the distribution of the corrected Positive and Negative Syndrome Scale percent change, or as a dichotomous variable defined as the number of patients scoring ≥30% from the corrected baseline Positive and Negative Syndrome Scale score. Genotyping was achieved with established polymerase chain reaction-restriction fragment length polymorphism methods.Results: With response treated as a continuous variable, the homozygous recessive rs2032582 genotypes (TT) who were simultaneously carriers of a loss-of-function CYP2D6 allele (*4 or *5) responded significantly worse than the rest of the patients. Comparison of genotype frequencies revealed a statistically significant association of the above combination. No significant association between chlorpromazine equivalents and the tested genotypes was detected. Conclusion:We have detected a possible interaction between ABCB1 and CYP2D6 in affecting response of psychotic patients to drug treatment, in a naturalistic setting.

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Section: Discussionmentioning

confidence: 99%

ABCB1 and CYP2D6 polymorphisms and treatment response of psychotic patients in a naturalistic setting

Papazisis

Goulas

Sarrigiannidis

et al. 2017

Human Psychopharmacology

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“…Rats exposed to cypermethrin during postnatal development and re-exposed at adulthood present decreased locomotor activity and motor coordination and those are accompanied by deficits in the dopaminergic system (Singh and others 2012). Prenatal exposure to cypermethrin followed by re-exposure at adulthood elicits a more pronounced expression of xenobiotic metabolizing P450 in brain (Singh and others 2013), which may have toxic consequences, as these enzymes activity are shown to affect both dopaminergic and serotonergic systems (Ingelman-Sundberg and others 2014; Shahabi and others 2008). …”

Section: How To Improve Safetymentioning

confidence: 99%

Developmental neurotoxicity of succeeding generations of insecticides

Abreu‐Villaça

Levin

2017

Environment International

136

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Insecticides are by design toxic. They must be toxic to effectively kill target species of insects. Unfortunately, they also have off-target toxic effects that can harm other species, including humans. Developmental neurotoxicity is one of the most prominent off-target toxic risks of insecticides. Over the past seven decades several classes of insecticides have been developed, each with their own mechanisms of effect and toxic side effects. This review covers the developmental neurotoxicity of the succeeding generations of insecticides including organochlorines, organophosphates, pyrethroids, carbamates and neonicotinoids. The goal of new insecticide development is to more effectively kill target species with fewer toxic side effects on non-target species. From the experience with the developmental neurotoxicity caused by the generations of insecticides developed in the past advice is offered how to proceed with future insecticide development to decrease neurotoxic risk.

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“…However, it is not yet clear whether their endogenous role and local drug metabolism can affect treatment with psychiatric drugs. This topic however, is beyond the scope of this review; for further reading see (56) and. P-glycoprotein (P-gp) is a plasma membrane efflux pump encoded by the ABCB1 gene which acts as a drug transport mechanism, actively exporting drugs from cerebrospinal fluid to blood.…”

Section: Pharmacodynamic Pharmacogeneticsmentioning

confidence: 98%

Pharmacogenomics of Antidepressant and Antipsychotic Treatment: How Far Have We Got and Where Are We Going?

et al. 2020

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Polymorphic Expression of Cyp2C19 and Cyp2D6 in the Developing and Adult Human Brain Causing Variability in Cognition, Risk for Depression and Suicide: The Search for the Endogenous Substrates

Cited by 29 publications

References 23 publications

ABCB1 and CYP2D6 polymorphisms and treatment response of psychotic patients in a naturalistic setting

ABCB1 and CYP2D6 polymorphisms and treatment response of psychotic patients in a naturalistic setting

Developmental neurotoxicity of succeeding generations of insecticides

Pharmacogenomics of Antidepressant and Antipsychotic Treatment: How Far Have We Got and Where Are We Going?

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