Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and antipsychotic-induced metabolic disturbances in first-episode schizophrenia patients

2016 ◽  
Vol 33 (S1) ◽  
pp. S104-S104 ◽  
Author(s):  
B. Misiak ◽  
Ł. Łaczmański ◽  
K. Słoka ◽  
E. Szmida ◽  
R. Ślęzak ◽  
...  
Keyword(s):  
Weight Gain ◽  
Gene Polymorphisms ◽  
Methylenetetrahydrofolate Reductase ◽  
Serum Levels ◽  
Mthfr Gene ◽  
First Episode ◽  
Metabolic Disturbances ◽  
Competing Interest ◽  
First Episode Schizophrenia ◽  
677T Allele

IntroductionThere is a scarcity of prospective studies addressing the influence of the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms on antipsychotic-induced metabolic changes in first-episode schizophrenia (FES) patients.ObjectivesWe aimed at investigating metabolic side effects of second-generation antipsychotics (SGAs) with respect to the MTHFR gene polymorphisms in FES patients.MethodsPolymorphisms in the MTHFR gene (C677T and A1298C) were investigated with respect to changes in body mass index (BMI) and waist circumference (WC) together with serum levels of glucose, lipids, homocysteine, vitamin B12 and folate after 12 weeks of treatment with SGAs in 135 FES patients.ResultsThe 677TT genotype was associated with significantly higher BMI, WC and serum levels of triglycerides, as well as significantly lower folate levels at baseline. Additionally, the 677T allele was associated with significantly lower folate levels at baseline. The 677CC homozygotes had significantly higher increase in BMI and serum levels of triglycerides. The 677TT genotype predicted significantly higher increase in homocysteine levels and significantly higher decrease in folate levels. These associations were also significant in the allelic analysis. Only the patients with the 677T allele had significantly lower folate levels and significantly higher homocysteine levels at the follow-up. The 677T allele was also related to significantly lower increase in WC. The 1298CC homozygotes had significantly higher weight gain in the course of treatment with SGAs.ConclusionsThe MTHFR gene polymorphisms might predict antipsychotic-induced weight gain in FES patients. In addition, the MTHFR C677T polymorphism might be also predictive with respect to other metabolic adversities of SGAs.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Probiotic supplements reduce antipsychotic-induced metabolic disturbances in drug-naïve first-episode schizophrenia

2021 ◽  
Author(s):  
Dongyu Kang ◽  
Fengyu Zhang ◽  
Ye Yang ◽  
Chenchen Liu ◽  
Jingmei Xiao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Gain ◽  
Metabolic Disturbance ◽  
First Episode ◽  
Controlled Clinical Trial ◽  
Fasting Insulin ◽  
Metabolic Disturbances ◽  
Drug Naïve ◽  
Level Of Significance ◽  
First Episode Schizophrenia

ABSTRACTProbiotic supplements have demonstrated efficacy in improving metabolic abnormalities and may prevent antipsychotic-induced metabolic disturbance and weight gain. A few studies in rodents have found that antipsychotic-induced metabolic dysfunctions are associated with the altered composition of gut microbiota. Here, we conducted a randomized-controlled clinical trial to determine the effectiveness and safety of probiotic supplements on antipsychotic-induced metabolic disturbance and weight gain. Patients with drug-naïve first-episode schizophrenia were randomized to receive either olanzapine plus probiotics or olanzapine monotherapy and scheduled to evaluate with follow-ups for clinical and metabolic profiles. After a treatment of 12 weeks with addition of probiotics, the increase of mean fasting insulin was significantly lower than olanzapine monotherapy. Insulin resistance increased considerably in the olanzapine plus probiotics, but also significantly lower than olanzapine monotherapy. We noted a difference in the increase in body mass index and body weight between treatments at a nominal level of significance, but it became non-significant after adjusting for appetite increase. Probiotics concurrently used with olanzapine is effective and safe in attenuating antipsychotic-induced elevation of fasting insulin and insulin resistance, but not the weight gain in drug-naïve first-episode schizophrenia. Further study is warranted to assess the longer-term maintenance of efficacy and safety.

Combination of aripiprazole and olanzapine in first episode psychosis patient with metabolic syndrome: A case report

2017 ◽  
Vol 41 (S1) ◽  
pp. S755-S756
Author(s):  
I. Licanin ◽  
H. Senad
Keyword(s):  
Metabolic Syndrome ◽  
Complete Blood Count ◽  
Mental Health Center ◽  
First Episode ◽  
Metabolic Disturbances ◽  
The Metabolic Syndrome ◽  
Schizophrenia Spectrum ◽  
Patient Reported ◽  
Competing Interest ◽  
First Episode Schizophrenia

There are numerous factors that predispose patients with schizophrenia to develop metabolic syndrome and become overweight including: physical passivity, unhealthy diet and anti-psyhotic treatment. The prevalence of anti-psychotic-related metabolic disturbances has been reported to vary from 23% to 50% and clozapine and olanzapine had the most pronounced potential to cause metabolic syndrome. We present the case of 32-year-old male who has been diagnosed with first episode schizophrenia spectrum psychosis and has been treated for 3 months in the community mental health center. He was medication–compliant and was prescribed olanazapine 10 mg a day and had initial remission of symptoms. The reason behind referral to our department of psychiatry was development of metabolic syndrome. Immediately upon admission to our department basic panel blood tests (minerals, creatinin, glucose, tryglicerides and cholesterol) as well as complete blood count were done. Patient reported gaining weight of more than 5 kilograms since the initiation of the olanzapine treatment. Results of the performed metabolic tests in addition to abnormal BMI and slightly higher blood pressure have indicated presence of metabolic syndrome. In order to try to reverse metabolic syndrome aripiprazole was commenced adjunctive to olanzapine. During the first week the dosage of aripiprazole was 2.5 mg/day, second week 5 mg/day and then increased to 10 mg a day. Three weeks after adding aripiprazole to olanzapine lab values of holesterol, triglycerides, fasting glucose as well as BMI were significantly lowered and symptoms of the metabolic syndrome were mitigated. Treatment was well tolerated.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Brain Metabolic Abnormalities in Schizophrenia Patients

2017 ◽  
Vol 41 (S1) ◽  
pp. s802-s802
Author(s):  
M. Amorim ◽  
A. Moreira ◽  
A. Marques ◽  
T. Summavielle
Keyword(s):  
Glucose Metabolism ◽  
Insulin Signalling ◽  
Serum Levels ◽  
Phosphoglycerate Mutase ◽  
First Episode ◽  
Metabolic Disturbances ◽  
Elevated Glucose ◽  
Pubmed Search ◽  
Drug Naïve ◽  
Competing Interest

IntroductionMain schizophrenia symptoms result from abnormalities in brain function, such as hypofrontality and structural deficits on the prefrontal-thalamic-cerebellar circuit, as shown in brain imaging studies in first-episode SCZ patients. Whether metabolic alterations may be underlying these events is being studied thoroughly.Objectives/aimsTo assess brain metabolic disturbances in first episode and/or drug-naïve SCZ patients.MethodsWe conducted a literature review through Pubmed search for MeSH: schizophrenia, metabolism, glucose, insulin, brain. Controlled studies on first episode and/or drug-naïve SCZ patients were included.ResultsLower metabolic activity in the frontal regions of the brain is associated to an increase in norepinephrine transmission and decrease in dopaminergic transmission with reduced dopamine efflux in the frontal cortex. This seems to lead to cellular changes resulting in resulting lower blood flow and glucose demand. Molecular analysis of postmortem SCZ patients’ brains has indicated alterations in glucose metabolism and insulin signalling pathways, showing evidence for prefrontal cortex decreased expression of glucose metabolism, namely glycolytic enzymes such as glyceraldehyde 3-phosphate dehydrogenase, hexokinase, phosphoglycerate mutase, enolase and pyruvate kinase and decreased levels and phosphorylation of the insulin receptor and insulin signalling proteins AKT1 and GSK3β. Significantly elevated glucose concentrations in cerebrospinal fluid were observed in SCZ patients, but with no serum levels differences. A SCZ brain specific increased glucose could be explained by preferential utilization of lactate, predominantly produced by astrocytes, over glucose as an energy substrate.ConclusionsAbnormalities in brain glucose metabolism and insulin signalling seem to appear in early stages of SCZ, suggesting a role in SCZ onset and pathophysiology.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Correlation between Methylenetetrahydrofolate Reductase Polymorphisms and Hepatocellular Carcinoma: A Meta-Analysis

2019 ◽  
Vol 74 (3) ◽  
pp. 251-256 ◽  
Author(s):  
Hailong Su ◽  
Guo Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Polymorphisms ◽  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Random Effect ◽  
Recessive Model ◽  
Mthfr Gene ◽  
Systematic Research ◽  
The Relationship ◽  
Random Effect Models

Background: The correlation between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and hepatocellular carcinoma (HCC) remains controversial. Objectives: We performed this study to better assess the relationship between MTHFR gene polymorphisms and the likelihood of HCC. Methods: A systematic research of PubMed, Medline, and Embase was performed to retrieve relevant articles. ORs and 95% CIs were calculated. Results: A total of 15 studies with 8,378 participants were analyzed. In overall analyses, a significant association with the likelihood of HCC was detected for the rs1801131 polymorphism with fixed-effect models (FEMs) in recessive comparison (p = 0.002, OR 0.62, 95% CI 0.43–0.82). However, no positive results were detected for the rs1801133 polymorphism in any comparison. Further subgroup analyses revealed that the rs1801131 polymorphism was significantly associated with the likelihood of HCC in Asians with both FEMs (recessive model: p < 0.0001, OR 0.42, 95% CI 0.29–0.62; allele model: p = 0.004, OR 1.20, 95% CI 1.06–1.35) and random-effect models (recessive model: p = 0.002, OR 0.47, 95% CI 0.29–0.75). Nevertheless, we failed to detect any significant correlation between the rs1801133 polymorphism and HCC. Conclusions: Our findings indicated that the rs1801131 polymorphism may serve as a genetic biomarker of HCC in Asians.

scholarly journals Serum Levels of HCY, MIF, and hs-CRP Correlate with Glycolipid Metabolism in Adults with Never-Medicated First-Episode Schizophrenia

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xiao Zhong ◽  
Qin Ao ◽  
Fei Xing
Keyword(s):  
Waist Circumference ◽  
Rating Scale ◽  
Serum Levels ◽  
First Episode ◽  
Healthy Controls ◽  
Glycolipid Metabolism ◽  
Hs Crp ◽  
Positive Correlations ◽  
First Episode Schizophrenia ◽  
Negative Syndrome

Objective. It has been reported that the prevalence of metabolic syndrome (MS) in multiepisode patients with schizophrenia is 35.3%, which is 2- to 4-fold higher than in the general population. The study is designed to compare the glycolipid metabolism in patients with first-episode schizophrenia (FES) with sex- and age-matched healthy controls to investigate changes in serum levels of homocysteine (Hcy), macrophage migration inhibitory factor (MIF), and high-sensitive C-reactive protein (hs-CRP) and their relationships with the glycolipid metabolism in patients with FES. Methods. His case-control study included 88 patients diagnosed with FES and 88 sex- and age-matched healthy controls. Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS), and 17-item Hamilton Rating Scale for Depression (HAMD-17). Patients with FES were classified into MS and non-MS groups. Results. There were significant differences in the education level, body mass index (BMI), and waist circumference between the patients with FES and healthy controls (all p > 0.05 ). The patients with FES had higher levels of FPG and blood glucose at the oral glucose tolerance test (OGTT) (2 h glucose) concomitant with higher proportion of impaired glucose tolerance (IGT) and homeostasis model assessment of insulin resistance (HOMA2-IR) than healthy controls (all p < 0.001 ). It was revealed that the patients with FES showed higher serum levels of Hcy, MIF, and hs-CRP than healthy controls (all p < 0.001 ). The serum level of Hcy shared positive correlations with the score of PANSS totals (r = 0.551) and the negative syndrome of the PANSS scale (r = 0.494). The serum levels of MIF and hs-CRP was only positively correlated with the negative syndrome of the PANSS scale (r = 0.320 and r = 0.446). The level of Hcy shared positive correlations with the levels of FPG, 2 h glucose, and HOMA2-IR; the level of MIF was only positively correlated with the level of HOMA2-IR; the level of hs-CRP had a positive correlation with both levels of FPG and 2 h glucose (all p < 0.001 ). The levels of Hcy, MIF, and hs-CRP all shared positive correlations with the TG level and negative correlations with the HDL-C level (all p < 0.001 ). There were remarkable differences between the MS and non-MS groups with regard to BMI, waist circumference, negative subscale of the PANSS scale, FPG, TG, and HDL-C (all p < 0.05 ). Elevated levels of Hcy, MIF, and hs-CRP were detected in the MS group compared to the non-MS group (all p < 0.05 ). Conclusion. These findings suggest that increased concentrations of HCY, MIF, and hs-CRP may contribute to the abnormal glycolipid metabolism in the context of schizophrenia.

scholarly journals The Role of Butyric Acid in Treatment Response in Drug-Naïve First Episode Schizophrenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Xue Li ◽  
Xiaoduo Fan ◽  
Xiuxia Yuan ◽  
Lijuan Pang ◽  
Shaohua Hu ◽  
...  
Keyword(s):  
Treatment Response ◽  
Butyric Acid ◽  
Serum Levels ◽  
First Episode ◽  
Healthy Controls ◽  
Significant Difference ◽  
Drug Naïve ◽  
First Episode Schizophrenia ◽  
Risperidone Treatment

Background: Butyric acid, a major short-chain fatty acid (SCFA), has an important role in the microbiota–gut–brain axis and brain function. This study investigated the role of butyric acid in treatment response in drug-naïve first episode schizophrenia.Methods: The study recruited 56 Chinese Han schizophrenia inpatients with normal body weight and 35 healthy controls. Serum levels of butyric acid were measured using Gas Chromatography-Mass Spectrometer (GC-MS) analysis at baseline (for all participants) and 24 weeks after risperidone treatment (for patients). Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) for patients at both time points.Results: At baseline, there was no significant difference in serum levels of butyric acid between patients and healthy controls (p = 0.206). However, there was a significant increase in serum levels of butyric acid in schizophrenia patients after 24-week risperidone treatment (p = 0.030). The PANSS total and subscale scores were decreased significantly after 24-week risperidone treatment (p's &lt; 0.001). There were positive associations between baseline serum levels of butyric acid and the reduction ratio of the PANSS total and subscale scores after controlling for age, sex, education, and duration of illness (p's &lt; 0.05). Further, there was a positive association between the increase in serum levels of butyric acid and the reduction of the PANSS positive symptoms subscale scores (r = 0.38, p = 0.019) after controlling for potential confounding factors.Conclusions: Increased serum levels of butyric acid might be associated with a favorable treatment response in drug-naïve, first episode schizophrenia. The clinical implications of our findings were discussed.

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