scholarly journals Prediction of Clinical Symptoms of Schizophrenia Based on Comt Methylation Marker

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Nour El Huda Abd Rahim ◽  
Mohd Nabil Fikri Rahim ◽  
Norsidah Ku Zaifah ◽  
Hanisah Mohd Noor ◽  
Kartini Abdullah ◽  
...  

Introduction: The dopamine hypothesis of schizophrenia is based on the fact that hyperdopaminergic state is involved in causing psychosis and antipsychotic drugs block the dopamine receptor. COMT regulates the homeostatic levels of neurotransmitter dopamine in the synapses and plays a role in the neurocognitive function. The dysregulation of dopamine in the prefrontal cortex influences the cognitive function and the severity of the psychotic symptoms in schizophrenia. During epigenetic event, methylated COMT gene may cause reduction in its expression and contribute to the clinical presentation of schizophrenia. Therefore, the aim of this study was to assess the feasibility of using COMT DNA methylation for the prediction of specific psychotic presentation of schizophrenia. Materials and method: In this study, 138 schizophrenia patients were recruited from the Psychiatry Clinic, Hospital Tengku Ampuan Afzan, Kuantan Pahang. Genomic DNA from peripheral blood was subjected to the Methylight Taqman® analysis for quantitative measurement of the COMT DNA methylation. The psychopathological symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Results: The regression analysis showed that the Positive and Excited subdomains of PANSS were significant predictors of COMT hypomethylation (β= -0.288, p= -0.031; β= - 0.288, p= -0.031). The Excited subdomain of PANSS was negatively correlated with COMT DNA methylation (r 2 = -0.380, p= 0.000) as well as the Depressed subdomain (r 2 = -0.288, p= 0.001). Conclusion: The relationship between DNA methylation of COMT with the positive, excited and depressed symptoms might indicate the epigenetic role of COMT gene in the manifestation of schizophrenia.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dandan Li ◽  
Fengyan Zhang ◽  
Lu Wang ◽  
Yifan Zhang ◽  
Tingting Yang ◽  
...  

Abstract Objective Numerous studies have identified impaired decision making (DM) under both ambiguity and risk in adult patients with schizophrenia. However, the assessment of DM in patients with adolescent-onset schizophrenia (AOS) has been challenging as a result of the instability and heterogeneity of manifestations. The Iowa Gambling Task (IGT) and Game of Dice Task (GDT), which are frequently used to evaluate DM respectively under ambiguity and risk, are sensitive to adolescents and neuropsychiatric patients. Our research intended to examine the performance of DM in a relatively large sample of patients with AOS using the above-mentioned two tasks. We also aimed to take a closer look at the relationship between DM and symptom severity of schizophrenia. Methods We compared the performance of DM in 71 patients with AOS and 53 well-matched healthy controls using IGT for DM under ambiguity and GDT for DM under risk through net scores, total scores and feedback ration. Neuropsychological tests were conducted in all participants. Clinical symptoms were evaluated by using Positive and Negative Syndrome Scale (PANSS) in 71 patients with AOS. Pearson’s correlation revealed the relationship among total score of DM and clinical and neuropsychological data. Results Compared to healthy controls, patients with AOS failed to show learning effect and had a significant difference on the 5th block in IGT and conducted more disadvantageous choices as well as exhibited worse negative feedback rate in GDT. Apart from DM impairment under risk, diminished DM abilities under ambiguity were found related to poor executive function in AOS in the present study. Conclusions Our findings unveiled the abnormal pattern of DM in AOS, mainly reflected under the risky condition, extending the knowledge on the performance of DM under ambiguity and risk in AOS. Inefficient DM under risk may account for the lagging impulse control and the combined effects of developmental disease. In addition, our study demonstrated that the performance on IGT was related to executive function in AOS.


2015 ◽  
Vol 27 (4) ◽  
pp. 221-227 ◽  
Author(s):  
Li Su ◽  
Jianxiong Long ◽  
Runde Pan ◽  
Xinfeng Xie ◽  
Xixiang Mao ◽  
...  

BackgroundNRGNis one of the most promising candidate genes for schizophrenia based on function and position. Therefore, this study aimed to examine the genetic association of this polymorphism with schizophrenia in the Zhuang and Han populations of south China.Subjects and methodsA total of 282 patients (188 Han and 94 Zhuang) and 282 healthy subjects (188 Han and 94 Zhuang) were recruited. Of these, 246 schizophrenia patients underwent an assessment of psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS). A TaqMan genotyping assay method was used to determine the genotypes.ResultsWe did not find a significant association of rs12807809 polymorphism with schizophrenia in the total pooled samples, or in the separate ethnic groups. However, in Han schizophrenia patients, quantitative data analyses showed that the CC genotype of the rs12807809 polymorphism was associated with PANSS aggression subscale score and activation subscale score. Furthermore, carriers of the C allele of rs12807809 polymorphism among Han schizophrenia patients had higher scores of general, activation, depression, aggression, and global symptoms than the T allele carriers.ConclusionIn conclusion rs12807809 polymorphism may not contribute to the risk of schizophrenia but influence the clinical symptoms of schizophrenia in the Han population.


2012 ◽  
Vol 201 (4) ◽  
pp. 306-312 ◽  
Author(s):  
Rajeev Krishnadas ◽  
Sameer Jauhar ◽  
Susan Telfer ◽  
Somashekara Shivashankar ◽  
Robin G. McCreadie

BackgroundReasons for the increased prevalence of cigarette smoking in schizophrenia are unclear. Studies assessing clinical symptoms have sampled heterogeneous populations, with discrepant findings.AimsTo examine the relationship between clinical features, social adjustment and nicotine dependence in a geographically defined population of people with schizophrenia.MethodCross-sectional clinical study of 131 people with schizophrenia in Nithsdale, Scotland.ResultsSmokers were younger, mostly males and three times more likely to be unemployed. Those with severe nicotine dependence had greater scores on the positive subscale of the Positive and Negative Syndrome Scale (PANSS), and were prescribed higher doses of antipsychotic. Those with mild–moderate dependence had greater scores on the PANSS negative subscale. Greater symptom severity was associated with poorer social adjustment. Psychopathology and social adjustment were similar in quitters and never-smokers.ConclusionsOur findings indicate an association between nicotine dependence, clinical symptoms and social adjustment in schizophrenia. Although causal links cannot be inferred, identifying the relationship between nicotine dependence and psychopathology may have some value in the management of smoking in schizophrenia. Further longitudinal studies are required to explore this relationship.


2020 ◽  
Vol 11 ◽  
Author(s):  
Xue Yang ◽  
Hui Zhao ◽  
Xuebing Liu ◽  
Qin Xie ◽  
Xiaoliang Zhou ◽  
...  

Background: Cytokine levels can be changed in methamphetamine (METH) use disorders (MUDs) and primary psychosis. The present study assessed serum levels of some kinds of interleukins (ILs) in METH-associated psychosis (MAP) and their relationships with psychotic symptoms and cognitive dysfunction.Methods: Serum IL-2R, IL-6, IL-8, and IL-10 levels were examined by chemiluminescence assays in MAP patients (n = 119) and healthy controls (n = 108). The Positive and Negative Syndrome Scale (PANSS) and Montreal Cognitive Assessment (MOCA) were administered.Results: Serum levels of IL-6 and IL-8 were significantly increased in MAP patients (all p < 0.05). There was a negative relationship between IL-2R levels and PANSS positive (P) subscale scores (r = −0.193, p = 0.035). IL-6, IL-8 and IL-10 levels were all negatively correlated with the naming, delayed recall and orientation subscores on the MOCA (r = −0.209, p = 0.022; r = −0.245, p = 0.007; r = −0.505, p < 0.001, respectively).Conclusions: Our results indicate that immune disturbances are related to MAP and that IL-2R, IL-6, IL-8, and IL-10 are associated with the severity of psychotic symptoms and cognitive function impairment.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tarik Dahoun ◽  
Matthew M. Nour ◽  
Robert A. McCutcheon ◽  
Rick A. Adams ◽  
Michael A. P. Bloomfield ◽  
...  

Abstract Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmental risk factors sensitize the dopamine system to increase the risk of psychotic symptoms, but this remains to be tested in humans. We used [11C]-(+)-PHNO positron emission tomography to measure striatal dopamine-2/3 receptor (D2/3R) availability and ventral striatal dexamphetamine-induced dopamine release in healthy participants (n = 24). The relationships between dexamphetamine-induced dopamine release, dexamphetamine-induced positive psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS), and childhood trauma using the Childhood Trauma Questionnaire (CTQ) were assessed using linear regression and mediation analyses, with childhood trauma as the independent variable, dexamphetamine-induced dopamine release as the mediator variable, and dexamphetamine-induced symptoms as the dependent variable. There was a significant interaction between childhood trauma and ventral striatal dopamine release in predicting dexamphetamine-induced positive psychotic symptoms (standardized β = 1.83, p = 0.003), but a mediation analysis was not significant (standardized β = −0.18, p = 0.158). There were no significant effects of dopamine release and childhood trauma on change in negative (p = 0.280) or general PANSS symptoms (p = 0.061), and there was no relationship between ventral striatal baseline D2/3R availability and positive symptoms (p = 0.368). This indicates childhood trauma and dopamine release interact to influence the induction of positive psychotic symptoms. This is not consistent with a simple sensitization hypothesis, but suggests that childhood trauma moderates the cognitive response to dopamine release to make psychotic experiences more likely.


2020 ◽  
Author(s):  
Maitane Oscoz Irurozqui ◽  
◽  
Maria Guardiola-Ripoll ◽  
Carmen Almodóvar-Payà ◽  
Salavador Sarró ◽  
...  

Objectives. To evaluate the association of cannabis use, genes of the endocannabinoid system and their interaction on clinical symptoms and cognitive performance in patients with a first-episode of pyschosis. Background. The role of both cannabis use and individual genetic background has been shown in the risk for psychosis. However, the influence of cannabis and variability at endocannabinoid genes on the psychosis outcome still remains inconclusive. Materials and Methods. The sample comprised 43 Caucasian individuals with a first-episode of psychosis (mean age(sd)=25.80(6.39) years, 76.7% males, 51.2% cannabis users).There were no differences in age and sex between cannabis users and non-users. Genetic variability was assessed by genotyping one Single Nucleotide Polymorphism (SNP) in each gene (CNR1-rs1049353 and CNR2-rs2501431). Clinical (PANSS, GAF) and neuropsychological (WAIS, WMS, BADS) scales were administered. Results and conclusions. Genotypic frequencies did not differ between cannabis users and non-users. Cannabis use was associated with better manipulative abilities (IQ-M-WAIS, p=0.029) and better executive function (BADS, p=0.036). CNR1-T allele carriers presented higher disorganized and negative syndrome scores (p=0.001 and p=0.044, respectively). The interaction models evidenced a combined effect of CNR1 and cannabis use on the negative syndrome-PANSS (p=0.037). These results suggest the role of cannabis use and genetic background on cognitive and psychopathological outcomes in first-episode psychosis. However, evidence is still scant, and further investigation in larger samples is needed.


2021 ◽  
Vol 12 (2) ◽  
pp. 204380872110199
Author(s):  
Si-Sheng Huang ◽  
Cheng-Chen Chang

Impaired insight in patients with schizophrenia results in less satisfactory clinical outcomes. This study was conducted to investigate the relationship between insight and individual psychopathological dimensions in inpatients with schizophrenia using a self-report questionnaire. In this study, 90 patients with schizophrenia aged 18–75 years admitted in the acute psychiatric ward of a medical center in Taiwan were enrolled. Patient insight was measured using the Self-Appraisal of Illness Questionnaire (SAIQ), and psychopathological dimensions were measured using the Positive and Negative Syndrome Scale (PANSS) and its five-factor structure model. A higher SAIQ score indicates greater insight. In bivariate correlation analyses, statistically significant correlations were observed between age, single marital status, educational level, and positive, excited, and depressed symptom factor of the PANSS and SAIQ score. In regression analyses, age and excited and depressed symptom factors were significantly associated with SAIQ score. No significant association was observed between insight and neurocognitive functions. Considering demographic characteristics, psychopathology, and neurocognition, in the acute phase of schizophrenia, younger patients with less severe excited symptoms and more severe depressive symptoms had greater insight.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cristian Carmeli ◽  
Zoltán Kutalik ◽  
Pashupati P. Mishra ◽  
Eleonora Porcu ◽  
Cyrille Delpierre ◽  
...  

AbstractIndividuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.


2021 ◽  
Author(s):  
Tianyu Dong ◽  
Xiaoyan Wei ◽  
Qianting Qi ◽  
Peilei Chen ◽  
Yanqing Zhou ◽  
...  

Abstract Background: Epigenetic regulation plays a significant role in the accumulation of plant secondary metabolites. The terpenoids are the most abundant in the secondary metabolites of plants, iridoid glycosides belong to monoterpenoids which is one of the main medicinal components of R.glutinosa. At present, study on iridoid glycosides mainly focuses on its pharmacology, accumulation and distribution, while the mechanism of its biosynthesis and the relationship between DNA methylation and plant terpene biosynthesis are seldom reports. Results: The research showed that the expression of DXS, DXR, 10HGO, G10H, GPPS and accumulation of iridoid glycosides increased at first and then decreased with the maturity of R.glutinosa, and under different concentrations of 5-azaC, the expression of DXS, DXR, 10HGO, G10H, GPPS and the accumulation of total iridoid glycosides were promoted, the promotion effect of low concentration (15μM-50μM) was more significant, the content of genomic DNA 5mC decreased significantly, the DNA methylation status of R.glutinosa genomes was also changed. DNA demethylation promoted gene expression and increased the accumulation of iridoid glycosides, but excessive demethylation inhibited gene expression and decreased the accumulation of iridoid glycosides. Conclusion: The analysis of DNA methylation, gene expression, and accumulation of iridoid glycoside provides insights into accumulation of terpenoids in R.glutinosa and lays a foundation for future studies on the effects of epigenetics on the synthesis of secondary metabolites.


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