scholarly journals Association of СОМТ, DRD2/ANKK1, MTHFR, MIR 137, DNMT3B polymorphisms with the clinical features of schizophrenia patients in acute stage and remission

Author(s):  
H. S. Kandratsenka ◽  
N. G. Danilenko ◽  
I. M. Haylaenka ◽  
O. A. Skugarevsky ◽  
V. Marshe ◽  
...  

Updated view of genetic features of schizophrenia based on rare SNPs/CNVs with a huge influence on a disease and common SNPs with a small effect of each allele is presented. Altogether these genetic factors are acting to create neuropathophysiological disturbances observed in schizophrenia. Association of five polymorphisms MIR137 rs1625579, DRD2/ANKK1 rs1800497, MTHFR rs1801133, DNMT3B rs2424913, СОМТ rs4680 with the risk of schizophrenia in the Belarusian population, the level of symptoms of schizophrenia patients assessed by PANSS in the acute stage and remission, cognitive impairments, and treatment trajectory of schizophrenia patients during antipsychotic treatment were analyzed. The A/A-genotype of СОМТ rs4680 (р = 0.008) and the С/С-genotype of MTHFR rs1801133 (р = 0.02) are associated with the risk of schizophrenia among Belarusians. The T-allele of MTHFR rs1801133 is a risk factor of positive symptoms (р = 0.02). Combining the C/C-genotype (DNMT3B rs2424913) and the G-allele (COMT rs4680) is associated with a significant difference in negative symptoms level between men and women. The polymorphism of СОМТ rs4680 (р < 0.05) and the combination of СОМТ rs4680 + DRD2/ANKK1 rs1800497 (р = 0.005) as well as MTHFR rs1801133 + DNMT3B rs2424913 (р = 0.006) are related to the cognitive parameters measured by the WCST and Stroop test respectively. Schizophrenia patients who are the G-allele carriers of MIR137 rs1625579 demonstrated a more favorable negative symptom trajectory in comparison to Т/Тhomozygotes (F = 2.2, p = 0.03). The trajectory of negative symptoms (F = 2.2, p = 0.03) and general psychopathological symptoms (F = 4.3, p = 0.0001) is different between men and women under antipsychotic treatment. These differences are associated with a minor amount of alleles of MIR137 rs1625579, DRD2/ANKK1 rs1800497, MTHFR rs1801133 polymorphic sites.

2021 ◽  
Vol 7 (1) ◽  
pp. e02-e02
Author(s):  
Somaieh Ashrafi ◽  
Seyyed Mohammad Ghaffari ◽  
Hatam Boostani ◽  
Somaieh Raz ◽  
Negar Ebadi ◽  
...  

Introduction: Statins such as simvastatin are recently introduced as agents that may have beneficial effects in schizophrenia regarding their prominent anti-inflammatory properties. Objectives: This study was designed to evaluate the effects of simvastatin on schizophrenia symptoms. Patients and Methods: In a double-blinded randomized clinical trial, 40 hospitalized schizophrenia patients (according to the DSM-IV-TR criteria) were studied for 6 weeks. One group of the patients (n=20) received simvastatin (with the dose of 40 mg/d) and the other group received (n=20) placebo. The patients were evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia symptoms. Data were analyzed with mixed model repeated measure ANOVA, t test, and χ2 test or Fischer’s exact test by SPSS software. The significant cutoff was considered at P<0.05. Results: The mean age of the patients was 34.05±9.74 years and 50% of them were men. There was not a significant difference between the two groups regarding negative symptoms reduction. Conclusion: Our study demonstrated that adding simvastatin on atypical antipsychotic treatment had no significant beneficial effects on the negative and positive symptoms in patients with schizophrenia disorder. Trial Registration: The trial protocol was approved by the Iranian Registry of Clinical Trials (identifier: IRCT2017052034046N1; https://en.irct.ir/trial/26134, ethical code; ETH-457).


2019 ◽  
Vol 45 (4) ◽  
pp. 622-631 ◽  
Author(s):  
Yuya Mizuno ◽  
Robert A. McCutcheon ◽  
Stefan P. Brugger ◽  
Oliver D. Howes

AbstractTwo important clinical questions are whether there is a subtype of schizophrenia which responds differently to clozapine relative to other antipsychotics, and whether greater efficacy of clozapine is dependent on the degree of treatment-resistance. The authors address this by examining both variability and magnitude of response in patients treated with clozapine and other antipsychotics for both treatment-resistant schizophrenia (TRS) and non-resistant schizophrenia. Double-blind randomised controlled trials comparing clozapine with other antipsychotics in patients with schizophrenia were identified using five databases. Standard deviations and means of change in total, positive, and negative symptoms were extracted. Variability ratio (VR) and coefficient of variation ratio (CVR) were used to quantify relative variability in symptom change. Hedges’ g was used to quantify mean differences. Ten TRS studies (n = 822) and 29 non-TRS studies (n = 2566) were meta-analysed. Relative variability in change of total symptoms did not differ significantly between clozapine and other antipsychotics in TRS studies (VR = 1.84; 95%CI, 0.85–4.02). These findings were similar with CVR, and for positive and negative symptoms. Clozapine was superior to other antipsychotics in improving total symptoms in both TRS (g = 0.34; 95%CI, 0.13–0.56) and non-TRS (g = 0.20; 95%CI, 0.08–0.32) studies. Furthermore, clozapine was superior in improving positive symptoms in both study groups, but not for negative symptoms. Pooled effect sizes showed no significant difference between TRS and non-TRS studies. These findings do not support a subtype of schizophrenia which responds specifically to clozapine. Clozapine is more effective than other antipsychotics irrespective of treatment-resistance, arguing for its use more generally in schizophrenia. PROSPERO CRD42018086507


2017 ◽  
Vol 41 (S1) ◽  
pp. s806-s806
Author(s):  
P. Conus ◽  
M. Fournier ◽  
L. Xin ◽  
P. Baumann ◽  
C. Ferrari ◽  
...  

PurposeRecent evidence points to a critical role of redox dysregulation induced oxidative stress in the pathophysiology of early phases of schizophrenia. An add-on trial with n-acetyl-cysteine (NAC) led to a reduction in negative symptoms in chronic schizophrenia patients. Aim of this study was to explore impact of addition of NAC to standard treatment in early psychosis (EP) patients.MethodsDouble-blind, randomized, placebo-controlled trial of addition of NAC, 2700 mg daily, to antipsychotic treatment over 6 months. Monthly assessment of PANSS, GAF, SOFAS and antipsychotics treatment; quantification of brain glutathione levels (GSHmPFC) by 1H-magnetic-resonance-spectroscopy and of blood cells glutathione (GSHBC) and glutathione peroxidase activity (GPxBC) as marker of oxidation status at the beginning and end of treatment.ResultsOverall, 63 patients were included. Spectroscopy data showed that GSHmPFC increased by +23% in the NAC group, while it tended to decrease by −5% in the placebo group (P = 0.005). No significant difference between NAC and placebo was observed on global changes in negative symptoms, positive symptoms or functional outcome. However, in patients with high-baseline oxidation status (GPxBC>22.3U/gHb), subgroup explorations revealed an improvement of positive symptoms over time compared to patients with low-baseline GPx (P = 0.02).ConclusionsWhile addition of NAC induced an increase of brain GSH, it had no impact on symptomatic and functional outcome in EP patients. However, in patients with high oxidation status, addition of NAC leads to significantly greater improvement in positive symptoms. Future studies on antioxidant interventions in EP should consider biomarker-guided treatment.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2016 ◽  
Vol 5 (11) ◽  
pp. 5041
Author(s):  
Farkhondeh Jamshidi ◽  
Ahmad Ghorbani ◽  
Sina Darvishi*

The abuse of some pesticides especially to suicide is one of the current problems of pesticides. Aluminum phosphide induced poisoning usually happens to suicide and sometimes it is due to accidental occupational exposure and in a few cases it has some criminal intensions. This study is conducted to evaluate patients poisoned with aluminum phosphide. In the present study the medical records of cases of poisoning with rice tablets (aluminum phosphide) hospitalized in Ahvaz Razi hospital is studied. Accordingly, a checklist is prepared that included demographic information of patients (age, gender) and information on patient records (information on poisoning) are completed using the patients’ medical records. The analysis of data is done by SPSS V22. 18 patients poisoned with rice tablet (aluminum phosphide) are studied. Results of the study show that 11 patients are male and seven are female. The mean patient age is 27.06 ±8.04 years that is 28 ±9 and 25 ±6.02 in men and women respectively. Statistical tests show no statistically significant difference in mean age in both genders (P> 0.05). Among patients, 11 subjects took aluminum phosphide to attempt suicide and 3 cases took it unintentionally and of course the reason is not mentioned in four cases. Among the patients who tried to commit suicide by taking aluminum phosphide, 6 cases are male and 5 cases are female that no statistically significant difference is observed between the genders in this respect (P> 0.05). In addition to the study of the complications caused by this poisoning and its mortality, it is recommended to responsible authorities to provide the necessary educations and treatments to prevent this type of poisoning.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aras Neriman ◽  
Yilmaz Hakan ◽  
Ucuncu Ozge

Abstract Background Schizophrenia is a multifactorial disease involving interactions between genetic and environmental factors. Vitamin D has recently been linked to many metabolic diseases and schizophrenia. Vitamin D plays essential roles in the brain in the context of neuroplasticity, neurotransmitter biosynthesis, neuroprotection, and neurotransmission. Vitamin D receptors are demonstrated in most brain regions that are related to schizophrenia. However, very few studies in the literature examine the effects of 25-hydroxyvitamin D (25OHD) on schizophrenia symptoms. Methods This study aimed to examine the effects of vitamin D replacement on positive, negative, and cognitive symptoms of schizophrenia. Serum 25OHD levels of 52 schizophrenia patients were measured. SANS and SAPS were used to evaluate the severity of schizophrenia symptoms, and the Wisconsin Card Sorting Test: CV4 was used for cognitive assessment. The study was completed with 40 patients for various reasons. The patients whose serum 25OHD reached optimal levels after vitamin D replacement were reevaluated with the same scales in terms of symptom severity. The SPSS 25 package program was used for statistical analysis. The Independent-Samples t-test was used to examine the relationship between the variables that may affect vitamin D levels and the vitamin D level and to examine whether vitamin D levels had an initial effect on the scale scores. Results The mean plasma 25OHD levels of the patients was 17.87 ± 5.54. A statistically significant relationship was found only between the duration of sunlight exposure and 25 OHD level (p < 0.05). The mean SANS and SAPS scores of the participants after 25OHD replacement (23.60 ± 15.51 and 7.78 ± 8.84, respectively) were statistically significantly lower than mean SANS and SAPS scores before replacement (51.45 ± 17.96 and 18.58 ± 15.59, respectively) (p < 0.001 for all). Only the total attention score was significantly improved after replacement (p < 0.05). Conclusion The data obtained from our study suggest that eliminating the 25OHD deficiency together with antipsychotic treatment can improve the total attention span and positive and negative symptoms in schizophrenia. The 25OHD levels should be regularly measured, replacement should be started when necessary, and the patients should be encouraged to get sunlight exposure to keep optimal 25OHD levels.


Author(s):  
Nadine S. Rögner ◽  
Veronika Mall ◽  
Martin Steinhaus

AbstractAn odorant screening by gas chromatography–olfactometry (GC–O) and a crude aroma extract dilution analysis (AEDA) applied to the volatiles isolated from a light and a dark liquid malt extract (LME) by solvent extraction and solvent-assisted flavour evaporation (SAFE) identified 28 odorants. Fifteen major odorants were subsequently quantitated and odour activity values (OAVs) were calculated as ratio of the concentration to the respective odour threshold value (OTV). Important odorants in the light LME included 3-(methylsulfanyl)propanal (OAV 1500), (E)-β-damascenone (OAV 430), and 4-ethenyl-2-methoxyphenol (OAV 91). In the dark LME, sotolon (OAV 780), 3-(methylsulfanyl)propanal (OAV 550), (E)-β-damascenone (OAV 410), acetic acid (OAV 160), and maltol (OAV 120) were of particular importance. To get an insight into the changes during malt extract production, the quantitations were extended to the malt used as the starting material for both LMEs. Addition of a minor amount of water to malt before volatile extraction was shown to be effective to cover the free as well as the bound malt odorants. Results showed that some LME odorants originated from the starting material whereas others were formed during processing. Important process-induced LME odorants included (E)-β-damascenone and 4-ethenyl-2-methoxyphenol in the light LME as well as maltol, sotolon, (E)-β-damascenone, and 2-methoxyphenol in the dark LME. In summary, the odorant formation during LME production was shown to be more important than the transfer of odorants from the malt.


2021 ◽  
Vol 52 (2) ◽  
pp. 792-803
Author(s):  
Marit Buhaug Folstad ◽  
Eli Ringdalen ◽  
Halvard Tveit ◽  
Merete Tangstad

AbstractThis work investigates the phase transformations in silica (SiO2) during heating to a target temperature between 1700 °C and 1900 °C and the effect of SiO2 polymorphs on the reduction reaction 2SiO2 + SiC = 3SiO + CO in silicon production. Different heating rates up to target temperature have been used to achieve the different compositions of quartz, amorphous silica and cristobalite. The different heating rates had a minor effect on the final composition, and longer time at temperatures > 1400 °C were necessary to achieve greater variations in the final composition. Heating above the melting temperature gave more amorphous silica and less cristobalite, as amorphous silica also may form from β-cristobalite. Isothermal furnace experiments were conducted to study the extent of the reduction reaction. This study did not find any significant difference in the effects of quartz, amorphous silica or cristobalite. Increased temperature from 1700 °C to 1900 °C increased the reaction rate.


Author(s):  
S. Fayyaz ◽  
N. Nkire ◽  
B. Nwosu ◽  
N. Amjad ◽  
A. Kinsella ◽  
...  

Objectives: As Ireland confronts the many challenges of broadening the introduction of early intervention services (EIS) for first episode psychosis (FEP) as national policy, this article describes Carepath for Overcoming Psychosis Early (COPE), the EIS of Cavan–Monaghan Mental Health Service, and presents prospective research findings during its first 5 years of operation. Methods: COPE was launched as a rural EIS with an embedded research protocol in early 2012, following an education programme for general practitioners (GPs). Here, operational activities are documented and research findings presented through to late 2016. Results: During this period, 115 instances of FEP were incepted into COPE, 70.4% via their GP and 29.6% via the Emergency Department. The annual rate of inception was 24.8/100,000 of population aged > 15 years and was 2.1-fold more common among men than women. Mean duration of untreated psychosis was 5.7 months and median time from first psychotic presentation to initiation of antipsychotic treatment was zero days. Assessments of psychopathology, neuropsychology, neurology, premorbid functioning, quality of life, insight, and functionality compared across 10 DSM-IV psychotic diagnoses made at six months following presentation indicated minimal differences between them, other than more prominent negative symptoms in schizophrenia and more prominent mania in bipolar disorder. Conclusions: COPE illustrates the actuality of introducing and the challenges of operating a rural EIS for FEP. Prospective follow-up studies of the 5-year COPE cohort should inform on the effectiveness of this EIS model in relation to long-term outcome in psychotic illness across what appear to be arbitrary diagnostic boundaries at FEP.


Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1800 ◽  
Author(s):  
Fabio Pagni ◽  
Umberto Malapelle ◽  
Claudio Doglioni ◽  
Gabriella Fontanini ◽  
Filippo Fraggetta ◽  
...  

A meeting among expert pathologists was held in 2019 in Rome to verify the results of the previous harmonization efforts on the PD-L1 immunohistochemical testing by scoring a representative series of non-small cell lung cancer (NSCLC) digital slides. The current paper shows the results of this digital experimental meeting and the expertise achieved by the community of Italian pathologists. PD-L1 protein expression was determined using tumor proportion score (TPS), i.e., the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. The gold standard was defined as the final PD-L1 score formulated by a panel of seven lung committed pathologists. PD-L1 status was clustered in three categories, namely negative (TPS < 1), low (TPS 1–49%), and high (TPS ≥ 50%). In 23 cases (71.9%) PD-L1 staining was performed using the companion diagnostic 22C3 pharmDx kit on Dako Autostainer, while in nine (28.1%) cases it was performed using the SP263 Ventana kit on BenchMark platform. A complete PD-L1 scoring agreement between the panel of experts and the participants was reached in 57.1% of cases, whereas a minor disagreement in 16.1% of cases was recorded. Italian pathologists performed best in strong positive cases (i.e., tumor proportion score TPS > 50%), whereas only 10.8% of disagreement with the gold standard was observed, and 55.6% regarded a single challenging case. The worst performance was achieved in the negative cases, with 32.0% disagreement. A significant difference resulted from the analysis of the data separated by the different clones used: 22.3% and 38.1% disagreement (p = 0.01) was found in the group of cases analyzed by 22C3 and SP263 antibody clones, respectively. In conclusion, this workshop record proposed the application of a digital pathology platform to share controversial cases in educational meetings as an alternative possibility for improving the interpretation and reporting of specific histological tools. Due to the crucial role of PD-L1 TPS for the selection of patients for immunotherapy, the identification of unconventional approaches as virtual slides to focus experiences and give more detailed practical verifications of the standard quality reached may be a considerable option.


1975 ◽  
Vol 55 (2) ◽  
pp. 225-233 ◽  
Author(s):  
H. KODAMA ◽  
M. D. WEBBER

Two specimens of hydroxy aluminum phosphate interlayer materials in montmorillonite clay were prepared with 7.20 meq Al and 11.29 meq H3PO4/g clay and with 14.40 meq Al and 22.58 meq H3PO4/g clay, and the resulting complexes studied by chemical and mineralogical methods. Both interlayer materials were slightly positively charged and except for different water contents their chemical compositions were almost identical. They contained Al, PO4 and H2O and a minor amount of Ca and approximated hydrous AlPO4∙nH2O. The mole ratios of Al:Ca:PO4:OH were 1.00:0.08:0.92:0.24 and 1.00:0.05:0.91:0.24, respectively. The interlayer materials appeared to be loosely packed and distributed sparsely in interspaces of the montmorillonite. The degree of packing was greater for the preparation with the larger amount of interlayer material. The materials increased the montmorillonite basal spacing to 23.3 Å under air-dry condition (30–40% relative humidity) but did not affect the lateral dimensions. The basal spacing varied somewhat with relative humidity at room temperature and decreased markedly as water was driven off by heating. Heat treatments between room temperature and 300 C sharply reduced the d001 spacings to 16.7 Å which persisted up to 700 C. It is postulated that the large basal spacings occur because the hydrated interlayer materials have a framework structure with tunnels along the c-axis. This being so, changes in the spacings with different humidities might result from the movement of water molecules among interstitial spaces existing around and between the loosely distributed molecules of interlayer material. The 16.7 Å spacing for the dehydrated phase corresponds to the sum of 7.0 Å, the edge dimension of an orthorhombic anhydrous AlPO4 and 9.7 Å, the silicate layer thickness.


Sign in / Sign up

Export Citation Format

Share Document