Variants of Dopamine and Serotonin Candidate Genes as Predictors of Response to Risperidone Treatment in First-Episode Schizophrenia

Ikeda, Masashi; Yamanouchi, Yoshio; Kinoshita, Yoko; Kitajima, Tsuyoshi; Yoshimura, Reiji; Hashimoto, Shuji; O'Donovan, Michael Conlon; Nakamura, Jun; Ozaki, Norio; Iwata, Nakao

doi:10.2217/14622416.9.10.1437

Cited by 108 publications

(114 citation statements)

References 47 publications

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“…This indicates a possible, partial role for the Taq1A polymorphism in response to aripiprazole (70). Two other previous studies in 2008 both also had positive findings in relation to Taq1A and clinical response to aripiprazole using the PANSS scale (71 [rs3803300] and AKT1-SNP5 [rs2494732]) were significantly associated with response to risperidone, using the PANSS scale (72).…”

Section: Pharmacodynamicsmentioning

confidence: 55%

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

Changasi

Shams

Pouget

et al. 2014

Translational Developmental Psychiatry

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Background and purpose: Antipsychotics (APs) are the primary method of treatment for schizophrenia and other psychotic disorders. Unfortunately, lengthy trial-and-error approaches are typically required to find the optimal medication and dosage due to a large interindividual variability with outcome to AP treatment. The literature has shown abundant evidence for a genetic component in individuals' responses to APs. Pharmacogenetic studies analyze specific genetic markers and their association with symptom improvement and occurrence of side effects with APs. This research aims to optimize AP drug treatment by usage of predictive testing and to personalize medicine. Recent findings: This review will highlight the most consistent findings in pharmacogenetics of APs and will update the reader on the clinical implications. This will include how genetic variants modulate AP drug levels, side effects, and therapeutic symptom improvement (i.e. response) to AP treatment. Summary: Several promising findings were obtained implicating gene variants of the dopamine receptor genes in addition to gene variants of serotonin receptors for response and common side effects. Notably, effect sizes appear to be particularly high in the genetics of side effects compared to response. One example is antipsychotic-induced weight gain where the leptin, HTR2C and in particular the melanocortin-4-receptor (MC4R) genes have been implicated in weight gain in children and adolescents. Consistent findings were also obtained for genes implicated in tardive dyskinesia and agranulocytosis. However, the most clinically relevant findings pertain to genes involved in drug metabolism such as the CYP2D6 and CYP2C19 genes which have been included in the first genetic test kits such as the Amplichip †

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Section: Pharmacodynamicsmentioning

confidence: 55%

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

Changasi

Shams

Pouget

et al. 2014

Translational Developmental Psychiatry

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“…Individuals with the Ser311Cys polymorphism, the fourth polymorphism of the gene, specifically the Ser/Ser genotype, were prone to respond to Risperidone treatment in a study with 123 Chinese participants [49] and demonstrated a decrease in cAMP synthesis inhibition in a study with 50 Japanese participants [50]. For the A-241G polymorphism, Asian individuals with A allele or A/A genotype showed a positive improvement to Risperidone treatment in a study with 125 Chinese participants [51] and in study with 120 Japanese participants [30]. However, American individuals with the A allele or A/A genotype showed a delayed response to Risperidone treatment in a study with 61 Caucasian and African American participants [44].…”

Section: Drd2mentioning

confidence: 96%

“…Two studies, one with a sample composed of 99 Chinese participants [28] and one with 123 Chinese participants [29] have shown a notable association among the T/T genotype and an improved response to Clozapine and Risperidone treatment in Han Chinese participants [28,29]. However, two other studies, one with 120 Japanese participants [30] and one with 173 Caucasian and African American participants [31], did not show any association between the treatment response and genetic variance of the 5HT6 gene (Table 1).…”

Section: Ht6mentioning

confidence: 99%

“…The second polymorphism of the gene, the Taq1B polymorphism, particularly the T allele, has been linked to an increased response rate in African Americans in a study with 232 Caucasian and African American participants [46]. Carriers of the third polymorphism, Taq1A, showed a higher response to antipsychotic medications in three different studies, one with 25 Japanese participants [47], one with 57 Caucasian participants [48] and one with 120 Japanese participants [30]. Individuals with the Ser311Cys polymorphism, the fourth polymorphism of the gene, specifically the Ser/Ser genotype, were prone to respond to Risperidone treatment in a study with 123 Chinese participants [49] and demonstrated a decrease in cAMP synthesis inhibition in a study with 50 Japanese participants [50].…”

Section: Drd2mentioning

confidence: 99%

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The Impact of Drug and Gene Interaction on the Antipsychotic Medication for Schizophrenia

Cho¹,

Contreras²,

Garza³

et al. 2017

Bipolar Disord

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Objective: Schizophrenia, a neuropsychiatric disorder, is known to be neurodevelopmentally progressive. Due to the extensive interindividual variability found in the responses of patients, management of schizophrenia has proven to be challenging. This interindividual variability to treatment could be justified by the variation of the enzymes in charge of metabolizing medications, especially those associated with cytochrome P450. Since genetic factors influence the phenotypic responses to drugs, researchers are involved in identifying schizophrenic genetic factors, which could impact responses and severe effects for commonly known neuroleptic drugs known as pharmacogenetics. In order to predict drug response at the personal level, genetic variants that determine drug effects need to be identified. Methods:We have chosen to investigate gene targets for risperidone and clozapine, two commonly administered drugs for the treatment of schizophrenia. The aim of this review is to contribute in the understanding of genetic influences on drug responses of risperidone and clozapine in schizophrenia. We reviewed original primary research articles, meta-analysis, and review publications on drug and gene interaction on the treatment of schizophrenia. Our main findings focused on schizophrenia, pharmacogenetics and cytochrome P450. Results and conclusion:After filtering our results to human species and English language, a total of 45 scientific articles were used for this review. A promising direction for future research in schizophrenia treatment lies behind the identification of the specific genetic contributors that affect drug response.

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“…Полиморфный вариант Variable Number Tandem Repeats (48-bp VNTR), состоящий из повторных участков, расположен-ный в 3-м ýкзоне, активно изучался, однако дал противоречивые данные c подавляющим боль-шинством негативных результатов [62]. VNTR считается особенно важным, так как кодирует участок рецептора, вовлеченного в стыковку с G-белком, и чем длиннее ýтот участок за счет повторений, тем меньше становится аффинность рецептора к клозипину [63].…”

Section: гены кодирующие продукты которые участвуют в фармакодинамиunclassified

Mechanisms of development of antipsychotic-induced metabolic disorders: pharmacogenetic aspect

Насырова¹,

Толмачев²,

Сычев³

et al. 2017

Bûll. sib. med.

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Основными препаратами для терапии психи-ческих расстройств шизофренического спектра являются антипсихотики, требующие длитель-ного применения. Антипсихотические препараты * Насырова Регина Фаритовна, e-mail: reginaf@bekhterev.ru. УДК 615.214.21-06:616-008.9 DOI: 10.20538/1682УДК 615.214.21-06:616-008.9 DOI: 10.20538/ -0363-2017 Для цитирования: Насырова Р.Ф., Толмачев М.Ю., Сычев Д.А., Яхин К.К., Незнанов Н.Г. Механизмы развития антипси-хотик-индуцированных метаболических нарушений: фармакогенетический аспект. РЕЗЮМЕАнтипсихотики являются основными лекарственными препаратами в терапии расстройств шизофре-нического спектра. Антипсихотические препараты требуют длительного применения, обладают узкой терапевтической широтой, большим спектром и выраженностью нежелательных лекарственных реак-ций, проявление которых во многом определяется генотипом пациента. Выраженность нежелательных лекарственных реакций у препаратов первой и второй генераций антипсихотиков различна.Применение атипичных антипсихотиков, в отличие от типичных, реже вызывает экстрапирамидные расстройства, но индуцирует, прежде всего, метаболические нарушения: изменение веса, дизрегуляцию метаболизма глюкозы, дислипидемию. Перечисленные нежелательные лекарственные реакции в значи-тельной мере снижают приверженность пациентов к терапии и могут привести к серьезным осложне-ниям в дальнейшем. Клинический опыт применения антипсихотиков показал, что выраженность неже-лательных реакций одного препарата, принимаемого различными пациентами, является вариабельным показателем в связи с полиморфизмом генов фармакокинетических и фармакодинамических факторов, задействованных в реализации фармакологического действия антипсихотиков. В связи с этим изучение влияния различных комбинаций полиморфных вариантов генов фармакокинетических и фармакодина-мических факторов на развитие антипсихотик-индуцированных метаболических нарушений является приоритетной задачей персонализированной психиатрии.Ключевые слова: фармакогенетика, антипсихотики, метаболические нарушения, набор веса, фарма-кодинамические факторы, фармакокинетические факторы.обладают узкой терапевтической широтой, боль-шим спектром и выраженностью нежелательных лекарственных реакций, проявление которых во многом определяется генотипом пациента [1]. Антипсихотики принято классифицировать на две категории: препараты первой генерации (FGAs) и препараты второй генерации (SGAs), также именуемые как типичные и атипичныеBulletin of Siberian Medicine. 2017; 16 (4): 30-41 31Обзоры и лекции антипсихотики. Данная классификация основа-на на механизме действия препаратов: способ-ностью блокировать D 2 -рецепторы к дофамину обладают как препараты первой, так и второй генерации антипсихотиков, но SGAs демонстри-руют значительно более низкую специфичность к D 2-рецептору и реализуют терапевтический ýф-фект через иные механизмы. В механизме дей-ствия атипичных антипсихотиков преобладает се-ротонин-дофаминовый антагонизм (5HT2A/D 2,3,4 ), который сочетается с выраженным аффинитетом к холинергическим, адренергическим и гистами-новы...

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Variants of Dopamine and Serotonin Candidate Genes as Predictors of Response to Risperidone Treatment in First-Episode Schizophrenia

Abstract: These data suggest that the SNPs in DRD2 and AKT1 may influence the treatment response to risperidone in schizophrenia patients.

Cited by 108 publications

References 47 publications

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

The Impact of Drug and Gene Interaction on the Antipsychotic Medication for Schizophrenia

Mechanisms of development of antipsychotic-induced metabolic disorders: pharmacogenetic aspect

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