Successful treatment with risperidone increases 5‐<scp>HT</scp> 3A receptor gene expression in patients with paranoid schizophrenia – data from a prospective study

Chen, Hongying; Fan, Yu; Zhao, Lei; Hao, Yong; Zhou, Xiajun; Guan, Yangtai; Li, Zezhi

doi:10.1002/brb3.798

Cited by 8 publications

(7 citation statements)

References 28 publications

(41 reference statements)

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“…However, Taraskina et al did not identify significant changes in the expression of 5-HT 2A or D 4 genes in PBMCs after 28 days of treatment with haloperidol or olanzapine (53). Also, successful treatment with risperidone has recently been found to increase the 5-HT3A receptor gene expression in patients with paranoid schizophrenia, indicating that the 5-HT3A receptor may be involved in the mechanism of risperidone effect (47). Our results are mixed in this regard.…”

Section: The Effect Of Antipsychotics On Dopamine and Serotonin Recepcontrasting

confidence: 75%

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Expression of Dopamine D1−4 and Serotonin 5-HT1A-3A Receptors in Blood Mononuclear Cells in Schizophrenia

et al. 2021

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Introduction: The aim of this study was to determine the mRNA expression profile of dopamine D1, D2, D3, D4 and serotonin 5-HT1A, 5-HT2A, and 5-HT3A receptors in peripheral blood mononuclear cells (PBMCs) in schizophrenia and the in vitro effect of antipsychotics on the expression of these receptors in PBMCs of healthy subjects.Materials and Methods: Twenty-seven patients with schizophrenia and 29 healthy controls were recruited for the study. All study subjects underwent thorough clinical assessment, including anthropometric and body composition measurements. The expression of mRNA for dopamine D1−4 and serotonin 5-HT1A−3A receptors was measured using quantitative RT-PCR in peripheral blood mononuclear cells. In vitro mRNA and protein expression of these receptors was measured using quantitative RT-PCR and Western Blotting in PBMCs cultured with quetiapine, haloperidol, aripiprazole, risperidone, olanzapine or clozapine at IC50, half of IC50, and one-quarter of IC50 concentrations.Results: The key finding was that the schizophrenia group demonstrated significantly higher mRNA expression of D1, D2 and D4 receptors (p < 0.001), and significantly lower mRNA expression of 5-HT3A receptors (p < 0.01). After adjusting for smoking, the mRNA expression of D1 lost its significance, while that of D3, 5-HT1A, 5-HT2A became significant (all three were lower in the schizophrenia group). These receptors also demonstrated different ratios of mRNA expression in the schizophrenia group. The in vitro experiments showed that high concentrations of antipsychotics influenced the mRNA and protein expression of all studied receptors.Conclusion: Schizophrenia patients display a distinctive pattern of dopamine and serotonin receptor mRNA expression in blood mononuclear cells. This expression is little affected by antipsychotic treatment and it may therefore serve as a useful diagnostic biomarker for schizophrenia.

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Section: The Effect Of Antipsychotics On Dopamine and Serotonin Recepcontrasting

confidence: 75%

“…Studies suggest that 5-HT 3A receptors are not involved in in the pathogenesis of schizophrenia ( 46 ). Also, their expression may change during antipsychotic treatment, but only in certain subgroups of patients: Chen et al report such changes only in responders to risperidone ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Expression of Dopamine D1−4 and Serotonin 5-HT1A-3A Receptors in Blood Mononuclear Cells in Schizophrenia

et al. 2021

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“…To elucidate the key brain areas involved in schizophrenia, we analyzed PET data acquired with schizophrenia patients. The neurotransmitter 5-HT itself can induce the release of certain other neurotransmitters in the prefrontal cortex, including dopamine [ 27 , 28 ]. In fact, as early as 1954, Wolley et al .…”

Section: Resultsmentioning

confidence: 99%

MiR-4763-3p targeting RASD2as a Potential Biomarker and Therapeutic Target for Schizophrenia

Wang¹,

Qi²,

Shi³

et al. 2022

Aging and disease

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Existing diagnostic methods are limited to observing appearance and demeanor, even though genetic factors play important roles in the pathology of schizophrenia. Indeed, no molecular-level test exists to assist diagnosis, which has limited treatment strategies. To address this serious shortcoming, we used a bioinformatics approach to identify 61 genes that are differentially expressed in schizophrenia patients compared with healthy controls. In particular, competing endogenous RNA network revealed the important role of the gene RASD2 , which is regulated by miR-4763-3p. Indeed, analysis of blood samples confirmed that RASD2 is downregulated in schizophrenia patients. Moreover, positron emission tomography data collected for 44 human samples identified the prefrontal and temporal lobes as potential key brain regions in schizophrenia patients. Mechanistic studies indicated that miR-4763-3p inhibits RASD2 by base-pairing with the 3’ untranslated region of RASD2 mRNA. Importantly, RASD2 has been shown to interact with β-arrestin2 , which contributes to the regulation of the DRD2-dependent CREB response element-binding protein pathway in the dopamine system. Finally, results obtained with a mouse model of schizophrenia revealed that inhibition of miR-4763-3p function alleviated anxiety symptoms and improved memory. The dopamine transporters in the striatal regions were significantly reduced in schizophrenia model mice as compared with wild-type mice, suggesting that inhibition of miR-4763-3p can lessen the symptoms of schizophrenia. Our findings demonstrate that miR-4763-3p may target RASD2 mRNA and thus may serve as a potential biomarker and therapeutic target for schizophrenia, providing a theoretical foundation for further studies of the molecular basis of this disease.

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“…The treatment response was determined by a reduction of more than 25% in the PANSS total score [31,32] . The PANSS reduction rate was calculated using the following formula: (baseline PANSS total score -follow-up PANSS total score)/(baseline PANSS total score − 30) [33] .…”

Section: Intervention Proceduresmentioning

confidence: 99%

Amisulpride Augmentation Therapy Improves Cognitive Performance and Psychopathology in Clozapine-resistant Treatment-refractory Schizophrenia (CTRS): a 12-week Randomized, Double-blind, Placebo-controlled Trial

Zhu

Liu

et al. 2022

Preprint

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BackgroundAlthough clozapine is an effective option for treatment-resistant schizophrenia (TRS), there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine. The main purposes of this randomized, double-blind, placebo-controlled trial was to explore the amisulpride augmentation efficacy on the psychopathological symptoms and cognitive function of CTRS patients. MethodsA total of 80 patients were recruited and randomly assigned to receive an initial clozapine plus amisulpride or clozapine plus placebo. Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Clinical Global Impression (CGI) scale scores, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Treatment Emergent Symptom Scale (TESS), laboratory measurements and electrocardiograms (ECG) were performed at baseline, week 6, and week 12. ResultsCompared with clozapine plus placebo group, clozapine plus amisulpride had lower PANSS total score, positive subscore and general psychopathology subscore at week 6 and week 12 (all p Bonferroni< 0.01). Furthermore, compared with clozapine plus placebo group, clozapine plus amisulpride showed improved RBANS language score at week 12 (p Bonferroni< 0.001). Clozapine plus amisulpride group had a higher treatment response rate (p = 0.04), lower scores of CGI severity (CGI-S) and CGI efficacy (CGI-E) at week 6 and week 12 than clozapine plus placebo (all p Bonferroni< 0.05). There were no differences in BMI, QT intervals or laboratory measurements between the groups. Our results demonstrate that amisulpride augmentation therapy can safely improve the psychiatric symptoms and cognitive performance of CTRS patients. ConclusionsOur study indicates that amisulpride augmentation therapy has important clinical significance for the treatment of CTRS to improve clinical symptoms and cognitive function with tolerability and safety.Trial registrationClinicaltrials.gov identifier- NCT03652974. Registered 31 August 2018, https://clinicaltrials.gov/ct2/show/NCT03652974

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Successful treatment with risperidone increases 5‐HT 3A receptor gene expression in patients with paranoid schizophrenia – data from a prospective study

Cited by 8 publications

References 28 publications

Expression of Dopamine D1−4 and Serotonin 5-HT1A-3A Receptors in Blood Mononuclear Cells in Schizophrenia

Expression of Dopamine D1−4 and Serotonin 5-HT1A-3A Receptors in Blood Mononuclear Cells in Schizophrenia

MiR-4763-3p targeting RASD2as a Potential Biomarker and Therapeutic Target for Schizophrenia

Amisulpride Augmentation Therapy Improves Cognitive Performance and Psychopathology in Clozapine-resistant Treatment-refractory Schizophrenia (CTRS): a 12-week Randomized, Double-blind, Placebo-controlled Trial

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