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Abstract 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.

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. [ABSTRACT FROM AUTHOR]

Abstract Background Schizophrenia (SCZ) is a severe and chronic psychiatric disorder with premature age-related physiological changes. However, numerous previous studies examined the epigenetic age acceleration in SCZ patients and yielded inconclusive results. In this study, we propose to explore the epigenetic age acceleration in drug-naive first-episode SCZ (FSCZ) patients and investigate whether epigenetic age acceleration is associated with antipsychotic treatment, psychotic symptoms, cognition, and subcortical volumes. Methods We assessed the epigenetic age in 38 drug-naive FSCZ patients and 38 healthy controls by using three independent clocks, including Horvath, Hannum and Levine algorithms. The epigenetic age measurements in SCZ patients were repeated after receiving 8 weeks risperidone monotherapy. Results Our findings showed significantly positive correlations between epigenetic ages assessed by three clocks and chronological age in both FSCZ patients and healthy controls. Compared with healthy controls, drug-naive FSCZ patients have a significant epigenetic age deceleration in Horvath clock (p = 0.01), but not in Hannum clock (p = 0.07) and Levine clock (p = 0.43). The epigenetic ages of Hannum clock (p = 0.002) and Levine clock (p = 0.01) were significantly accelerated in SCZ patients after 8-week risperidone treatment. However, no significant associations between epigenetic age acceleration and psychotic symptoms, cognitive function, as well as subcortical volumes were observed in FSCZ patients. Conclusion These results demonstrate that distinct epigenetic clocks are sensitive to different aspects of aging process. Further investigations with comprehensive epigenetic clock analyses and large samples are required to confirm our findings.

Background: Schizophrenia (SCZ) is a severe and chronic psychiatric disorder with premature age-related physiological changes. However, numerous previous studies examined the epigenetic age acceleration in SCZ patients and yielded inconclusive results. In this study, we propose to explore the epigenetic age acceleration in drug-naive first-episode SCZ (FSCZ) patients and investigate whether epigenetic age acceleration is associated with antipsychotic treatment, psychotic symptoms, cognition, and subcortical volumes. Methods: We assessed the epigenetic age in 38 drug-naive FSCZ patients and 38 healthy controls by using three independent clocks, including Horvath, Hannum and Levine algorithms. The epigenetic age measurements in SCZ patients were repeated after receiving 8 weeks risperidone monotherapy. Results: Our findings showed significantly positive correlations between epigenetic ages assessed by three clocks and chronological age in both FSCZ patients and healthy controls. Compared with healthy controls, drug-naive FSCZ patients have a significant epigenetic age deceleration in Horvath clock (p = 0.01), but not in Hannum clock (p = 0.07) and Levine clock (p = 0.43). The epigenetic ages of Hannum clock (p = 0.002) and Levine clock (p = 0.01) were significantly accelerated in SCZ patients after 8-week risperidone treatment. However, no significant associations between epigenetic age acceleration and psychotic symptoms, cognitive function, as well as subcortical volumes were observed in FSCZ patients. Conclusion: These results demonstrate that distinct epigenetic clocks are sensitive to different aspects of aging process. Further investigations with comprehensive epigenetic clock analyses and large samples are required to confirm our findings. [ABSTRACT FROM AUTHOR]

Abstract Background Biomarkers are now widely used in many fields of medicine, and the identification of biomarkers that predict antipsychotic efficacy and adverse reactions is a growing area of psychiatric research. Monoamine molecules of the peripheral bloodstream are possible prospective biomarkers based on a growing body of evidence indicating that they may reflect specific changes in neurotransmitters in the brain. The aim of this study was to detect peripheral biogenic amine indicators of patients with acute psychosis and to test the correlations between the biological measures studied and the psychopathological status of the patients. Methods This research included 60 patients with acute psychosis treated with olanzapine (n = 30) or haloperidol (n = 30). Here, we measured biogenic amine indicators, including mRNA levels of dopamine receptor D4 (DRD4) and the serotonin 2A receptor (5HTR2A), in peripheral blood mononuclear cells (PBMCs) using quantitative real-time polymerase chain reaction and serum dopamine concentrations by enzyme linked immunosorbent assay (ELISA). Psychopathological status was evaluated using psychometric scales. The assessments were conducted prior to and after 14 and 28 days of treatment. Results The administration of haloperidol, but not olanzapine, up-regulated 5HTR2A mRNA in a linear manner, albeit without statistical significance (p = 0.052). Both drugs had non-significant effects on DRD4 mRNA levels. Nevertheless, a positive correlation was found between DRD4 and 5HTR2A mRNA levels over a longitudinal trajectory, suggesting co-expression of the two genes. A significant positive correlation was observed between 5HTR2A mRNA levels and total Positive and Negative Syndrome Scale (PANSS) scores in both groups of patients before treatment. A significant correlation between baseline 5HTR2A mRNA levels and PANSS scores on days 14 and 28 of treatment remained for patients treated with olanzapine only. Moreover, a significant positive correlation was observed between blood serum dopamine levels and scores on extrapyramidal symptom scales in the olanzapine group. Conclusions The DRD4 and 5HTR2A genes are co-expressed in PBMCs during antipsychotic administration. Despite a correlation between the studied biogenic amine indicators and the psychopathological status of patients, reliable biomarkers of treatment response could not be determined.

Background: Biomarkers are now widely used in many fields of medicine, and the identification of biomarkers that predict antipsychotic efficacy and adverse reactions is a growing area of psychiatric research. Monoamine molecules of the peripheral bloodstream are possible prospective biomarkers based on a growing body of evidence indicating that they may reflect specific changes in neurotransmitters in the brain. The aim of this study was to detect peripheral biogenic amine indicators of patients with acute psychosis and to test the correlations between the biological measures studied and the psychopathological status of the patients. Methods: This research included 60 patients with acute psychosis treated with olanzapine (n=30) or haloperidol (n=30). Here, we measured biogenic amine indicators, including mRNA levels of dopamine receptor D4 (DRD4) and the serotonin 2A receptor (5HTR2A), in peripheral blood mononuclear cells (PBMCs) using quantitative real-time polymerase chain reaction and serum dopamine concentrations by enzyme linked immunosorbent assay (ELISA). Psychopathological status was evaluated using psychometric scales. The assessments were conducted prior to and after 14 and 28 days of treatment. Results: The administration of haloperidol, but not olanzapine, up-regulated 5HTR2A mRNA in a linear manner, albeit without statistical significance (p = 0.052). Both drugs had non-significant effects on DRD4 mRNA levels. Nevertheless, a positive correlation was found between DRD4 and 5HTR2A mRNA levels over a longitudinal trajectory, suggesting co-expression of the two genes. A significant positive correlation was observed between 5HTR2A mRNA levels and total Positive and Negative Syndrome Scale (PANSS) scores in both groups of patients before treatment. A significant correlation between baseline 5HTR2A mRNA levels and PANSS scores on days 14 and 28 of treatment remained for patients treated with olanzapine only. Moreover, a significant positive correlation was observed between blood serum dopamine levels and scores on extrapyramidal symptom scales in the olanzapine group. Conclusions: The DRD4 and 5HTR2A genes are co-expressed in PBMCs during antipsychotic administration. Despite a correlation between the studied biogenic amine indicators and the psychopathological status of patients, reliable biomarkers of treatment response could not be determined. [ABSTRACT FROM AUTHOR]

Background: Antipsychotic therapy can reduce severe symptoms of psychiatric disorders, however, data on school performance among children on such treatment are lacking. The objective was to explore school performance among children using antipsychotic drugs at the end of primary education. Methods: A cross-sectional study was conducted using the University Groningen pharmacy database linked to academic achievement scores at the end of primary school (Dutch Cito-test) obtained from Statistics Netherlands. Mean Cito-test scores and standard deviations were obtained for children on antipsychotic therapy and reference children, and statistically compared using analyses of covariance. In addition, differences in subgroups as boys versus girls, ethnicity, household income, and late starters (start date within 12 months of the Cito-test) versus early starters (start date > 12 months before the Cito-test) were tested. Results: In all, data from 7994 children could be linked to Cito-test scores. At the time of the Cito-test, 45 (0.6%) were on treatment with antipsychotics. Children using antipsychotics scored on average 3.6 points lower than the reference peer group (534.5 ± 9.5). Scores were different across gender and levels of household income (p < 0.05). Scores of early starters were significantly higher than starters within 12 months (533.7 ± 1.7 vs. 524.1 ± 2.6). Conclusion: This first exploration showed that children on antipsychotic treatment have lower school performance compared to the reference peer group at the end of primary school. This was most noticeable for girls, but early starters were less affected than later starters. Due to the observational cross-sectional nature of this study, no causality can be inferred, but the results indicate that school performance should be closely monitored and causes of underperformance despite treatment warrants more research. [ABSTRACT FROM AUTHOR]