Dataset Information

DRD2, DRD3, and HTR2A Single-Nucleotide Polymorphisms Involvement in High Treatment Resistance to Atypical Antipsychotic Drugs.

ABSTRACT:

Background

The objective of this study was to investigate the DRD2 rs1800497, rs1799732, rs1801028, DRD3 rs6280, and HTR2A rs6314, rs7997012, and rs6311 single-nucleotide polymorphism (SNP) correlations with resistance to second-generation antipsychotics (SGAs) in a real-world sample of patients with treatment-resistant mental disorders.

Methods

We divided 129 participants into a high treatment resistance (HTR) group (current treatment with two SGAs, or clozapine, or classic neuroleptics for a failure of previous SGAs trials) and a low treatment resistance (LTR) group (current treatment with one atypical antipsychotic). We used Next-Generation Sequencing on DNA isolated from peripheral blood samples to analyze the polymorphisms. We performed logistic regression to search for predictors of HTR membership.

Results

Conclusions

A diagnosis of schizophrenia and the DRD2 rs1799732, DRD3 rs6280, and HTR2A rs7997012 genotypes can predict high treatment resistance to SGAs.

SUBMITTER: Del Casale A

PROVIDER: S-EPMC10377184 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

DRD2, DRD3, and HTR2A Single-Nucleotide Polymorphisms Involvement in High Treatment Resistance to Atypical Antipsychotic Drugs.

Del Casale Antonio A Simmaco Maurizio M Modesti Martina Nicole MN Zocchi Clarissa C Arena Jan Francesco JF Bilotta Irene I Alcibiade Alessandro A Sarli Giuseppe G Cutillo Lorenzo L Antonelli Giulia G La Spina Enrico E De Luca Ottavia O Preissner Robert R Borro Marina M Gentile Giovanna G Girardi Paolo P Pompili Maurizio M

Biomedicines 20230724 7

<h4>Background</h4>The objective of this study was to investigate the <i>DRD2</i> rs1800497, rs1799732, rs1801028, <i>DRD3</i> rs6280, and <i>HTR2A</i> rs6314, rs7997012, and rs6311 single-nucleotide polymorphism (SNP) correlations with resistance to second-generation antipsychotics (SGAs) in a real-world sample of patients with treatment-resistant mental disorders.<h4>Methods</h4>We divided 129 participants into a high treatment resistance (HTR) group (current treatment with two SGAs, or clozap ...[more]

PMID: 37509727

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Project description:The beliefs that antipsychotic drugs (APDs) are 1) effective only to treat delusions and hallucinations (positive symptoms), 2) that typical and atypical APDs differ only in ability to cause extrapyramidal side effects, and 3) that their efficacy as antipsychotics is due solely to their dopamine D2 receptor blockade are outmoded concepts that prevent clinicians from achieving optimal clinical results when prescribing an APD. Atypical APDs are often more effective than typical APDs in treating negative symptoms, cognitive impairment, and mood symptoms as well as reducing the risk for suicide and decreasing aggression. This applies not only to those diagnosed with schizophrenia or schizoaffective disorder but also to bipolar disorder, major depression, and other psychiatric diagnoses. The greater advantage of an atypical APD is not evident in all patients for every atypical APD due, in part, to individual differences in genetic and epigenetic endowment and differences in the pharmacology of the atypical APDs, their mode of action being far more complex than that of the typical APDs. A common misconception is that among the atypical APDs, only clozapine is effective for reducing psychosis in treatment-resistant schizophrenia. Aripiprazole, lurasidone, olanzapine, and risperidone also can be more effective than typical APDs for treatment-resistant schizophrenia; clozapine is uniquely indicated for reducing the risk for suicide. The ability of the atypical APDs to improve cognition and negative symptoms in some patients together with lower propensity to cause tardive dyskinesia (an underappreciated advantage) leads to better overall outcomes. These advantages of the atypical APDs in efficacy and safety are due, in part, to initiation of synaptic plasticity via direct and indirect effects of the atypical APDs on a variety of proteins, especially G proteins, and release of neurotrophins (e.g., brain-derived neurotrophic factor). The typical APDs beneficial effects on psychosis are mainly the result of D2 receptor blockade, which can be associated with serious side effects and lack of tolerability.

Project description:BACKGROUND: Ghrelin (GHRL) is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG) is a common side effect of the atypical antipsychotics (AAPs) used to treat schizophrenia (SZ). Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI). However, it is unclear whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there is no evidence of an association between GHRL polymorphisms and SZ or the therapeutic response to AAPs. We explored these potential associations by genotyping GHRL alleles in SZ patients and controls. We also examined the relation between these SNPs and changes in metabolic indices during AAP treatment in SZ subgroups distinguished by high or low therapeutic response. METHODS: Four SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C) were genotyped in 634 schizophrenia patients and 606 control subjects. RESULTS: There were no significant differences in allele frequencies, genotype distributions, or the distributions of two SNP haplotypes between SZ patients and healthy controls (P > 0.05). There was also no significant difference in symptom reduction between genotypes after 8 weeks of AAP treatment as measured by positive and negative symptom scale scores (PANSS). However, the -604 G/A polymorphism was associated with a greater BMI increase in response to AAP administration in both APP responders and non-responders as distinguished by PANSS score reduction (P < 0.001). There were also significant differences in WG when the responder group was further subdivided according to the specific AAP prescribed (P < 0.05). CONCLUSIONS: These four GHRL gene SNPs were not associated with SZ in this Chinese Han population. The -604 G/A polymorphism was associated with significant BW and BMI increases during AAP treatment. Patients exhibiting higher WG showed greater improvements in positive and negative symptoms than patients exhibiting lower weight gain or weight loss.

Project description:BackgroundPrescribing the optimal antipsychotic treatment to schizophrenia is very important as it is well established that patients have different sensitivity to the available antipsychotic drugs. The genotype of the HTR2A T102C (rs6313) polymorphism has been suggested to affect the efficacy of antipsychotic drugs, but the results of different studies have been inconsistent METHODS: In this study, a meta-analysis was used to ascertain the association between allele and genotype polymorphism of rs6313 and the efficacy of antipsychotic drugs. Related studies publicated from January 1995 to December 2021 were retrieved from PubMed, Embase, ScienceDirect, and Web of Science databases. The correlations between allele and genotype polymorphism of rs6313 and the responder rate and scale score reduction rate of antipsychotics were analyzed. In addition, subgroup analyses were performed on time, drug, and ethnicity.ResultsA total of 18 studies were included. The meta-analysis showed that allele and genotype polymorphisms at the rs6313 locus overall were not associated with antipsychotic drug responder rate or scale score reduction rate. Ethnicity subgroup analysis showed that antipsychotic drugs were more effective in patients with allele T in the Caucasian population. Indian patients with the TT genotype had the lowest scale score reduction rate and poor drug treatment effect. East Asian patients with the TC genotype had better treatment effect, whereas in patients with the CC genotype, the treatment was less effective. Drug subgroup analysis showed that patients with the TC genotype treated with clozapine had the highest responder rate and score reduction rate.ConclusionsThe association between rs6313 polymorphism and the efficacy of antipsychotic drugs is mainly influenced by drug and ethnicity. Caucasian patients with the T allele respond better to drug therapy, and Asian patients with TC genotype. The TC genotype was also a good predictor of the efficacy of clozapine treatment.

Dataset Information

DRD2, DRD3, and HTR2A Single-Nucleotide Polymorphisms Involvement in High Treatment Resistance to Atypical Antipsychotic Drugs.

Background

Methods

Results

Conclusions

Publications

DRD2, DRD3, and HTR2A Single-Nucleotide Polymorphisms Involvement in High Treatment Resistance to Atypical Antipsychotic Drugs.

Similar Datasets

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