Association of Risperidone Treatment Response With a Polymorphism in the 5-HT<sub>2A</sub> Receptor Gene

Lane, Hsien‐Yuan; Chang, Yue‐Cune; Chiu, Chih-Chiang; Chen, Mao-Liang; Hsieh, Min-Hua; Chang, Wei‐Cheng

doi:10.1176/appi.ajp.159.9.1593

Cited by 131 publications

(104 citation statements)

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“…These inconsistencies may be due to lack of power (modest sample size), differences in pharmacological histories, differences in time on study treatment or methods of response measurement. 26 In addition, as the aforementioned studies were done in Han Chinese 11,13,17 and Korean 14 populations, the SNPs analyzed may have less effect in African-American and white populations. In this analysis, we chose to use only data generated while the subjects received risperidone; however, as olanzapine and risperidone have some similarities in receptor activity, the additional data generated while subjects received olanzapine might have increased the power of this study.…”

Section: Discussionmentioning

confidence: 99%

“…In all, 22 SNPs were selected on the basis of prior knowledge of their involvement with response to risperidone or to other antipsychotic drugs. The selected SNPs and genes included ANKK1 (rs1800497 [4][5][6][7][8][9][10][11][12][13][14][15][16][17] Genotyping was performed by Cogenics (Newton, MA, USA) using Sequenom MassARRAY iPlex as previously described. 20 Statistical analysis African-American and white patients who had received at least one dose of risperidone between week 0 and study end (week 12) and who had consented to DNA testing were included in the analysis.…”

Section: Selection Of Snps and Genotypingmentioning

confidence: 99%

“…In the current study, we present results from an analysis of the association between antipsychotic response and 22 single-nucleotide polymorphisms (SNPs), earlier reported to be associated with antipsychotic response, [4][5][6][7][8][9][10][11][12][13][14][15][16][17] using data from a randomized, double-blind study of early response to a single drug (risperidone) in patients with schizophrenia, schizoaffective disorder or schizophreniform disorder. 18 The majority of patients in the trial were African-American and white adults, the former being a group that has been underrepresented in pharmacogenomic studies.…”

Section: Introductionmentioning

confidence: 99%

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Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia

et al. 2009

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Clinical trial data were evaluated for the association between 22 singlenucleotide polymorphisms (SNPs) and response in acutely ill patients diagnosed with schizophrenia, schizoaffective disorder or schizophreniform disorder, who were treated with oral risperidone. All patients in the exploratory (78 African Americans) and validation (65 whites) data sets received risperidone 2-6 mg per day over 2-12 weeks. Two SNPs were found to have significant associations with response to risperidone over 2-12 weeks in both African-American and white patients and had a consistent direction of effect in both cohorts. Metabotropic glutamate receptor (GRM3) SNP, rs724226, was associated with a change in the positive and negative syndrome scale (PANSS) total response. Catechol-O-methyltransferase (COMT) SNP, rs165599, was moderately associated with a change in the PANSS Negative score. The greater prevalence of poor-responder GRM3 and COMT alleles in white versus African-American patients might have a clinical significance in evaluating the ethnic-specific response to risperidone.

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Section: Discussionmentioning

confidence: 99%

Section: Selection Of Snps and Genotypingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia

et al. 2009

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“…170 A number of reports have associated a silent 5-HT 2A polymorphism, and a 102-T/C substitution, with response to clozapine and risperidone. 116,121,[123][124][125] This polymorphism is in complete LD with a À1438-G/A promoter polymorphism in Caucasian populations (the extent of linkage may vary in different ethnic groups). The G allele of this last polymorphism shows a lower promoter activity than the A allele 171 and may partly explain the associations with response.…”

Section: Pharmacodynamic Factorsmentioning

confidence: 99%

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

2007

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The last decade of research into the pharmacogenetics of antipsychotics has seen the development of genetic tests to determine the patients' metabolic status and the first attempts at personalization of antipsychotic treatment. The most significant results are the association between drug metabolic polymorphisms, mainly in cytochrome P450 genes, with variations in drug metabolic rates and side effects. Patients with genetically determined CYP2D6 poor metabolizer (PMs) status may require lower doses of antipsychotic. Alternatively, CYP2D6 ultrarapid matabolizers (UMs) will need increased drug dosage to obtain therapeutic response. Additionally, polymorphisms in dopamine and serotonin receptor genes are repeatedly found associated with response phenotypes, probably reflecting the strong affinities that most antipsychotics display for these receptors. In particular, there is important evidence suggesting association between dopamine 2 receptor (D2) polymorphisms (Taq I and À141-C Ins/Del) and a dopamine 3 receptor (D3) polymorphism (Ser9Gly) with antipsychotic response and drug-induced tardive dyskinesia. Additionally, there is accumulating evidence indicating the influence of a 5-HT2C polymorphism (À759ÀT/C) in antipsychotic-induced weight gain. Application of this knowledge to clinical practice is slowly gathering pace, with pretreatment determination of individual's drug metabolic rates, via CYP genotyping, leading the field. Genetic determination of patients' metabolic status is expected to bring clinical benefits by helping to adjust therapeutic doses and reduce adverse reactions. Genetic tests for the pretreatment prediction of antipsychotic response, although still in its infancy, have obvious implications for the selection and improvement of antipsychotic treatment. These developments can be considered as successes, but the objectives of bringing pharmacogenetic and pharmacogenomic research in psychiatric clinical practice are far from being realized. Further development of genetic tests is required before the concept of tailored treatment can be applied to psychopharmatherapy. This review aims to summarize the key findings from the last decade of research in the field. Current knowledge on genetic prediction of drug metabolic status, general response and drug-induced side effects will be reviewed and future pharmacogenomic and epigenetic research will be discussed.

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“…These studies have consistently shown that carriers of the C-allele show greater improvement, especially in regard to negative symptoms. A number of studies reported significant associations between the linked 5-HT 2A A-1438G and T102C receptor SNPs and response to atypical antipsychotics (mostly clozapine), but there are some discrepant results with respect to the risk-alleles for non-responding Arranz et al, 1998a;Arranz et al, 1998b;Joober et al, 1999;Yu et al, 2001;Lane et al, 2002;Hamdani et al, 2005; see also Arranz and de Leon, 2007). In addition, there are several studies reporting that there is no association between the T102C substitution and the therapeutic response to clozapine and other antipsychotics (Masellis et al, 1995;Nothen et al, 1995;Jonsson et al, 1996;Malhotra et al, 1996;Lin et al, 1999).…”

Section: Tph1 = Tryptophan Hydroxylasementioning

confidence: 99%

Serotonin and Schizophrenia

Quednow

Geyer

Halberstadt

2010

Handbook of Behavioral Neuroscience

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Although the serotonin hypothesis of schizophrenia is one of the oldest neurochemical hypotheses on the pathogenesis of this disease, it is still highly topical. The concept of how the serotonin system is involved in the origin and progress of schizophrenia has considerably changed over the past decades. Therefore, the present work will give an overview about the development and the current directions of the serotonin hypothesis of schizophrenia. In this regard, we will discuss the phenomenology of hallucinogenic drug action, model psychosis and translational research, post-mortem studies on receptors and transporters, imaging studies, antipsychotic drug action, neuroendocrine challenge studies, platelet and cerebrospinal fluid data, genetic association studies, developmental aspects, and the cross-talk between the glutamate and the serotonin system. In sum, there are several lines of evidence suggesting that the serotonin system plays a major role in the pathogenesis of at least a subpopulation of schizophrenia patients. Further studies are needed to better characterize patients whose psychotic symptoms are suspected to have a serotonergic origin. Serotonin and Schizophrenia AbstractAlthough the serotonin hypothesis of schizophrenia is one of the oldest neurochemical hypotheses on the pathogenesis of this disease, it is still highly topical. The concept of how the serotonin system is involved in the origin and progress of schizophrenia has considerably changed over the past decades.Therefore, the present work will give an overview about the development and the current directions of the serotonin hypothesis of schizophrenia. In this regard, we will discuss the phenomenology of hallucinogenic drug action, model psychosis and translational research, post-mortem studies on receptors and transporters, imaging studies, antipsychotic drug action, neuroendocrine challenge studies, platelet and cerebrospinal fluid data, genetic association studies, developmental aspects, and the cross-talk between the glutamate and the serotonin system. In sum, there are several lines of evidence suggesting that the serotonin system plays a major role in the pathogenesis of at least a subpopulation of schizophrenia patients. Further studies are needed to better characterize patients whose psychotic symptoms are suspected to have a serotonergic origin.3

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Association of Risperidone Treatment Response With a Polymorphism in the 5-HT_2A Receptor Gene

Abstract: These results suggest that variations in the 5-HT(2A) receptor gene may influence individual responses to risperidone.

Cited by 131 publications

References 9 publications

Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia

Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

Serotonin and Schizophrenia

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Association of Risperidone Treatment Response With a Polymorphism in the 5-HT2A Receptor Gene

Abstract: These results suggest that variations in the 5-HT(2A) receptor gene may influence individual responses to risperidone.

Cited by 131 publications

References 9 publications

Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia

Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

Serotonin and Schizophrenia

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Association of Risperidone Treatment Response With a Polymorphism in the 5-HT_2A Receptor Gene