Association Between the COMT Val158Met Polymorphism and Antipsychotic Efficacy in Schizophrenia: An Updated Meta-Analysis

Ma, Jianchao; Zhao, Mingzhe; Zhou, Wei; Li, Mo; Cong, Hui; Shen, Lu; Wang, Ting; Wu, Hao; Zhang, Na; Zhang, Zhiruo; He, Lin; Qin, Shengying

doi:10.2174/1570159x18666201023154049

Cited by 14 publications

(7 citation statements)

References 57 publications

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“…First, diverse ethnicities as genetic background plays an important role in antipsychotic treatment response. Second, response phenotype is a complicated trait, differences observed in different studies may be related to heterogeneity of definitions or criteria of response phenotype [15,39]. Third, different sample sizes may result in various outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, Rajagopal VM et al observed that patients with COMT Val/Met or Met/ Met genotype who also had DRD4 120-bp allele revealed a significantly better response to clozapine [20]. Additionally, a meta-analysis reported a significantly improved response in Met-allele carrier Asian and Caucasian patients [39]. COMT is a catabolic enzyme with functional connection to dopaminergic transmission, the first target of most antipsychotics [11,39].…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, a meta-analysis reported a significantly improved response in Met-allele carrier Asian and Caucasian patients [39]. COMT is a catabolic enzyme with functional connection to dopaminergic transmission, the first target of most antipsychotics [11,39]. Protein function and structure studies indicate that COMT Val-Met substitution causes a disruption in enzyme stability and decreases enzymatic activity [11,39].…”

Section: Discussionmentioning

confidence: 99%

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Association of DRD2, DRD4 and COMT genes variants and their gene-gene interactions with antipsychotic treatment response in patients with schizophrenia

Taheri,

Pirboveiri,

Sayyah

et al. 2023

BMC Psychiatry

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Antipsychotic drugs are the first line of treatment in schizophrenia; although antipsychotic responses indicate a wide interindividual variety in patients with schizophrenia. This study aimed to investigate the association between four polymorphisms in DRD2, DRD4 and COMT genes and their gene-gene interactions with antipsychotic treatment response in patients with schizophrenia. A total of 101 patients with schizophrenia were recruited and stratified in treatment responder and treatment resistant groups based on the published criteria of resistant to treatment using PANSS. Clinical and demographic factors were analyzed. Genomic DNA was extracted from whole blood and genotyping for the four polymorphisms were done by ARMS-PCR, PCR-RFLP and gap-PCR. Gene-gene interactions were analyzed by logistic regression. In case of DRD2 A-241G, G allele was significantly associated with resistant to treatment. Regarding DRD4 120-bp duplication, 240/240 genotype was significantly associated with resistant to treatment comparing to other genotypes in a dominant model. The genotype combination of DRD4 240/240 and COMT Val/Val was significantly associated with treatment resistant. Among DRD2 AA genotype, COMT met allele carriers which also had a 120 bp allele of DRD4 had a significantly better response to antipsychotics. Moreover, analysis of clinical and demographic factors demonstrated a significantly longer duration of hospitalization and higher chlorpromazine-equivalent daily dose in resistant to treatment patients. Discovering the polymorphisms which effect treatment response to antipsychotics will provide the possibility of genetic screening before starting an antipsychotic treatment which enhances the chance of responding to antipsychotics and decreases drugs side effects and costs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Association of DRD2, DRD4 and COMT genes variants and their gene-gene interactions with antipsychotic treatment response in patients with schizophrenia

Taheri,

Pirboveiri,

Sayyah

et al. 2023

BMC Psychiatry

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“…The COMT rs4680 variant (Val158Met), associated with reduced cortical dopamine [18], has been associated with response to second-generation antipsychotics [19,20]. A recent meta-analysis confirmed the strength of this association (Z = 6.709, p = 9.8 × 10 −12 ) [21]. Variants of the BDNF gene were associated with risperidone and clozapine response [22] and with treatment resistance [23].…”

Section: Pharmacogenetic Associations With Treatment Responsementioning

confidence: 97%

Clinical Utility and Implementation of Pharmacogenomics for the Personalisation of Antipsychotic Treatments

Hernandez,

Cullell,

Cendros

et al. 2024

Pharmaceutics

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Decades of pharmacogenetic research have revealed genetic biomarkers of clinical response to antipsychotics. Genetic variants in antipsychotic targets, dopamine and serotonin receptors in particular, and in metabolic enzymes have been associated with the efficacy and toxicity of antipsychotic treatments. However, genetic prediction of antipsychotic response based on these biomarkers is far from accurate. Despite the clinical validity of these findings, the clinical utility remains unclear. Nevertheless, genetic information on CYP metabolic enzymes responsible for the biotransformation of most commercially available antipsychotics has proven to be effective for the personalisation of clinical dosing, resulting in a reduction of induced side effects and in an increase in efficacy. However, pharmacogenetic information is rarely used in psychiatric settings as a prescription aid. Lack of studies on cost-effectiveness, absence of clinical guidelines based on pharmacogenetic biomarkers for several commonly used antipsychotics, the cost of genetic testing and the delay in results delivery hamper the implementation of pharmacogenetic interventions in clinical settings. This narrative review will comment on the existing pharmacogenetic information, the clinical utility of pharmacogenetic findings, and their current and future implementations.

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“…The Met allele is associated with reduced catabolic activity and is linked to greater tonic and reduced phasic striatal dopaminergic transmission [8]. In particular, COMT Val158Met polymorphism modifies enzymatic activity and, consequently, synaptic dopamine concentration in specific brain areas (prefrontal cortex and hippocampus) [9]. A PET study investigating D1 receptor density suggested that the Val allele was associated with lower levels activity of baseline dopamine in the cortex [10], although no associations were observed in a study on cortical D2 receptors [11].…”

Section: Introductionmentioning

confidence: 99%

Role of COMT V158M Polymorphism in the Development of Dystonia after Administration of Antipsychotic Drugs

et al. 2021

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Antipsychotics (APDs) represent the main pharmacological strategy in the treatment of schizophrenia; however, their administration often may result in severe adverse effects, such as extrapyramidal symptoms. Typically, dystonic movements are considered the result of impaired function and/or abnormalities of dopaminergic neurotransmission/signaling in the basal ganglia. The catechol O-methyltransferase (COMT) gene is located within the 22q11.2 region, and its product is an enzyme involved in transferring a methyl group from S-adenosylmethionine to catecholamines, including dopamine. Studies showed that COMT Val158Met polymorphism modifies enzymatic activity and, consequently, synaptic dopamine concentration in specific brain areas. We identified a patient with 22q11.2 deletion syndrome presenting with cervical and trunk dystonia after paliperidone administration, which persisted even after drug discontinuation. Given the patient’s genetic condition, we hypothesized that the dopaminergic dysfunction had been aggravated by COMT involvement, thus causing dystonia. In line with this hypothesis, we carried out a study on psychiatric patients in chronic treatment with APD to evaluate the distribution of the COMT Val158Met polymorphism and its role in the onset of adverse extrapyramidal symptoms. The study included four patients with dystonia after administration of APDs compared to 17 patients who never presented adverse drug reactions. Our data suggest that the Val/Val and Met/Met polymorphisms of the COMT gene are associated with a protective effect for the development of collateral extrapyramidal symptoms in patients treated with APDs, while the Val/Met genotype could be considered a risk factor for the development of dystonia after APDs administration.

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Association Between the COMT Val158Met Polymorphism and Antipsychotic Efficacy in Schizophrenia: An Updated Meta-Analysis

Cited by 14 publications

References 57 publications

Association of DRD2, DRD4 and COMT genes variants and their gene-gene interactions with antipsychotic treatment response in patients with schizophrenia

Association of DRD2, DRD4 and COMT genes variants and their gene-gene interactions with antipsychotic treatment response in patients with schizophrenia

Clinical Utility and Implementation of Pharmacogenomics for the Personalisation of Antipsychotic Treatments

Role of COMT V158M Polymorphism in the Development of Dystonia after Administration of Antipsychotic Drugs

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