Genetics of psychotropic medication induced side effects in two independent samples of bipolar patients

Autor: Daniel Souery, Diego Albani, Concetta Crisafulli, Alessandro Serretti, Armando Chierchia, Julien Mendlewicz, Rosalba Martines, Chiara Fabbri, Alberto Chiesa, Othman Sentissi, Gianluigi Forloni, Giovanni de Girolamo, Raffaella Calati
Přispěvatelé: Fabbri, C., Souery, D., Calati, R., Crisafulli, C., Chierchia, A., Albani, D., Forloni, G., Chiesa, A., Martines, R., Sentissi, O., Mendlewicz, J., De Girolamo, G., Serretti, A., Fabbri, C, Souery, D, Calati, R, Crisafulli, C, Chierchia, A, Albani, D, Forloni, G, Chiesa, A, Martines, R, Sentissi, O, Mendlewicz, J, De Girolamo, G, Serretti, A
Rok vydání: 2014
Předmět:
Adult
Male
medicine.medical_specialty
Bipolar Disorder
Drug-Related Side Effects and Adverse Reactions
Genotype
medicine.drug_class
Side effect Gene Pharmacogenetics Antipsychotic Antidepressant Mood stabilizer
medicine.medical_treatment
Sp4 Transcription Factor
Single-nucleotide polymorphism
Genome-wide association study
Pharmacology
Catechol O-Methyltransferase
Polymorphism
Single Nucleotide
Treatment of bipolar disorder
Glycogen Synthase Kinase 3
Internal medicine
Humans
Medicine
Genetic Predisposition to Disease
Receptor
Serotonin
5-HT2A
Bipolar disorder
Antipsychotic
Biological Psychiatry
Aged
Psychotropic Drugs
Glycogen Synthase Kinase 3 beta
business.industry
Brain-Derived Neurotrophic Factor
Psychotropic Drug
Nuclear Receptor Subfamily 1
Group F
Member 1
Mood stabilizer
Middle Aged
medicine.disease
Psychiatry and Mental health
Neurology
Antidepressant
Female
Neurology (clinical)
Drug-Related Side Effects and Adverse Reaction
business
Pharmacogenetics
Genome-Wide Association Study
Human
Signal Transduction
Zdroj: Journal of Neural Transmission. 122:43-58
ISSN: 1435-1463
0300-9564
Popis: The treatment of bipolar disorder (BD) usually requires combination therapies, with the critical issue of the emergence of adverse drug reactions (ADRs) and the possibility of low treatment adherence. Genetic polymorphisms are hypothesized to modulate the pharmacodynamics of psychotropic drugs, representing potential biological markers of ADRs. This study investigated genes involved in the regulation of neuroplasticity (BDNF, ST8SIA2), second messenger cascades (GSK3B, MAPK1, and CREB1), circadian rhythms (RORA), transcription (SP4, ZNF804A), and monoaminergic system (HTR2A and COMT) in the risk of neurological, psychic, autonomic, and other ADRs. Two independent samples of BD patients naturalistically treated were included (COPE-BD n = 147; STEP-BD n = 659). In the COPE-BD 34 SNPs were genotyped, while in the STEP-BD polymorphisms in the selected genes were extracted from the genome-wide dataset. Each ADRs group was categorized as absent-mild or moderate-severe and logistic regression with appropriate covariates was applied to identify possible risk genotypes/alleles. 58.5 and 93.5 % of patients were treated with mood stabilizers, 44.2 and 50.7 % were treated with antipsychotics, and 69.4 and 46.1 % were treated with antidepressants in the COPE-BD and STEP-BD, respectively. Our findings suggested that ST8SIA2 may be associated with psychic ADRs, as shown in the COPE-BD (rs4777989 p = 0.0017) and STEP-BD (rs56027313, rs13379489 and rs10852173). A cluster of RORA SNPs around rs2083074 showed an effect on psychic ADRs in the STEP-BD. Trends supporting the association between HTR2A and autonomic ADRs were found in both samples. Confirmations are needed particularly for ST8SIA2 and RORA since the few available data regarding their role in relation to psychotropic ADRs.
Databáze: OpenAIRE
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