Genetic susceptibility to tardive dyskinesia among schizophrenia subjects: IV. Role of dopaminergic pathway gene polymorphisms

Srivastava, Vibhuti; Varma, Panchami G.; Prasad, Shyam Baboo; Semwal, Prachi; Nimgaonkar, Vishwajit L.; Lerer, Bernard; Deshpande, Smita N.; Thelma, B.K.

doi:10.1097/01.fpc.0000184957.98150.0f

Cited by 76 publications

(63 citation statements)

References 67 publications

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“…In a somewhat surprising result, Liou et al 203 found no association between the D3 Ser9Gly polymorphism and TD in 216 Chinese schizophrenic patients (uncorrected for age), but reported association with heterozygosity for a BDNF Val66Met polymorphism. Srivastava et al 204 also failed to find association between D3 polymorphism and TD, but reported association between COMT, the enzyme that controls dopamine turnover, and TD, a finding not confirmed by other independent studies. [205][206][207]224 Similarly, MAOA and MAOB, two monoamine oxidases also involved in dopamine degradation, have been investigated and not found to contribute to TD, 207 suggesting that factors controlling dopamine metabolism are not involved.…”

Section: Prediction Of Side Effectsmentioning

confidence: 86%

“…Two recent studies have reported association between D4 polymorphisms and drug-induced TD. A gene 120 bp duplication and the long allele of the D4 LPR were reported to decrease the risk of TD, 204,224 increasing the evidence supporting the involvement of dopamine receptors in susceptibility to TD. The D3 Ser9Gly polymorphism was also associated with neuroleptic induced akathisia, 239 a common side effect which is thought to be triggered by alterations in nucleus accumbeus D3 activity.…”

Section: Prediction Of Side Effectsmentioning

confidence: 98%

“…Only one report suggested association between D2 polymorphisms and TD, 229 but no evidence was found by other groups. 204,[223][224][225][226][227][228] Similarly, no association was found when investigating D1 polymorphisms and a polymorphism in the dopamine transporter (DAT) in relation to TD, 204 and no association was found between D2 and D3 polymorphisms and tardive distonia, an uncommon druginduced movement disorder, in a pilot study on nine patient sufferers. 240 Serotonin inhibition of dopamine function may also contribute to the pathological events related to movement disorders.…”

Section: Prediction Of Side Effectsmentioning

confidence: 99%

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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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Section: Prediction Of Side Effectsmentioning

confidence: 86%

Section: Prediction Of Side Effectsmentioning

confidence: 98%

Section: Prediction Of Side Effectsmentioning

confidence: 99%

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

2007

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“…Han et al 55 included only male Korean patients and found a significant association between COMT val158met genotypes and alleles on the one hand and TD on the other with protective effect for the Met allele, Val-Met and Met-Met genotype compared to the Val and Val-Val reference groups, but not for EPS. Srivastava et al 56 studied four SNPs of COMT and TD, and found a significant genotypic association for COMT val158met with a protective effect for the Met-Met genotype, as well as significant allelic and genotypic association for genotype GG with 408 C > G (exon 4) with increased risk for the G allele, CG and GG genotype compared to the C and CC reference groups. Associated haplotypes also yielded significant results.…”

Section: Catechol-o-methyltransferasementioning

confidence: 99%

Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions

Bakker¹,

Harten²,

2008

Mol Psychiatry

136

117

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Despite accumulating evidence pointing to a genetic basis for tardive dyskinesia, results to date have been inconsistent owing to limited statistical power and limitations in molecular genetic methodology. A Medline, EMBASE and PsychINFO search for literature published between 1976 and June 2007 was performed, yielding 20 studies from which data were extracted for calculation of pooled estimates using meta-analytic techniques. Evidence from pooled data for genetic association with tardive dyskinesia (TD) showed (1) in COMT val158met , using Val-Val homozygotes as reference category, a protective effect for Val-Met heterozygotes (OR = 0.63, 95% CI: 0.46-0.86, P = 0.004) and Met carriers (OR = 0.66, 95% CI: 0.49-0.88, P = 0.005); (2) in Taq1A in DRD2, using the A1 variant as reference category, a risk-increasing effect for the A2 variant (OR = 1.30, 95% CI: 1.03-1.65, P = 0.026), and A2-A2 homozygotes using A1-A1 as reference category (OR = 1.80, 95% CI: 1.03-3.15, P = 0.037); (3) in MnSOD Ala9Val, using Ala-Ala homozygotes as reference category, a protective effect for Ala-Val (OR = 0.37, 95% CI: 0.17-0.79, P = 0.009) and for Val carriers (OR = 0.49, 95% CI: 0.24-1.00, P = 0.047). These analyses suggest multiple genetic influences on TD, indicative of pharmacogenetic interactions. Although associations are small, the effects underlying them may be subject to interactions with other loci that, when identified, may have acceptable predictive power. Future genetic research will take advantage of new genomic knowledge.

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“…We previously demonstrated the contribution of some of the genes from the dopaminergic pathway in the genesis of TD (DRD4 120bp dup; COMT 408C>G and Val158Met; Srivastava et al 2006). The CYP450 family of genes modified only the severity (CYP1A2*1C and CYP2D6*4; Tiwari et al 2005aTiwari et al , 2005bTiwari et al , 2006 and genes from the serotonergic pathway are not involved in either the development or severity of TD (Deshpande et al 2005).…”

Section: Nih Public Accessmentioning

confidence: 99%

Genetic susceptibility to Tardive Dyskinesia in chronic schizophrenia subjects: Role of oxidative stress pathway genes

Thelma

Tiwari

Deshpande³

et al. 2007

Schizophrenia Research

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Keywordsnorth India; Tardive Dyskinesia; oxidative stress; NOS3; NQO1; Single nucleotide polymorphisms; association Tardive Dyskinesia (TD) is a severe debilitating movement disorder with a potentially irreversible course developing in schizophrenia patients under long term treatment with classical neuroleptics. Its development in a subset of patients (~20-25%), familial nature, and concordance amongst twins indicate a possible genetic basis (for review see Muller et al. 2004). In addition to the classical dopaminergic pathway genes, oxidative stress mediated neurotoxic damage is also an important hypothesis proposed to explain the development of TD. Considerable support to OS hypothesis comes from the observations of increased lipid peroxidation in cerebrospinal fluid in patients with TD and antioxidants such as vitamin E alleviate TD symptoms (Adler et al. 1999; for review see Lohr, 2003). Recently a novel antioxidant AD4 has been reported to reduce haloperidol induced vacuous chewing moments in rats (Sadan et al. 2005).In this study, genes involved in the maintenance of cellular redox balance namely, superoxide dismutase 2 (SOD2; MnSOD; Ala9Val), Uncoupling protein 2 (UCP2; 45bp del/ins), neuronal nitric oxide synthase (nNOS; NOS1; His902His, rs2682826), endothelial NOS (eNOS; NOS3; 27bp ins/del), glutathione S transferase (GST; GSTMI, TI; Presence/Null; GSTPI, Ile105Val) and NADPH: quinone oxidoreductase 1 (NQO1, Pro187Ser) were analysed. Schizophrenia patients with TD (n=96) and without TD (n=239) were recruited for the study. SNPs were genotyped using PCR-RFLP and allelic, genotypic and haplotypic association was tested using χ 2 test. Further, to test whether severity of TD was influenced by genotype, mean AIMS score was compared across the genotypic categories for each of the polymorphism using Kruskal Wallis H test.

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Genetic susceptibility to tardive dyskinesia among schizophrenia subjects: IV. Role of dopaminergic pathway gene polymorphisms

Abstract: Our study presents a detailed analysis of the possible role of dopaminergic genes in the genesis of TD. DRD4 and COMT genes were observed to be the most important candidates in North Indian schizophrenia subjects. These suggestive associations need to be investigated in replicate studies.

Cited by 76 publications

References 67 publications

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

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

Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions

Genetic susceptibility to Tardive Dyskinesia in chronic schizophrenia subjects: Role of oxidative stress pathway genes

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