Transition to psychosis: Evaluation of the first-degree relatives of patients with schizophrenia

Objective: Schizophrenia and other psychoses have devastating personal and social impacts and many efforts have been devoted to study prodromal syndromes for psychosis in order to achieve earlier detection and interventions. However, only few studies have been performed in developing countries on this subject, and there is a dearth of evidence in the Iranian population. In this study, we focused on conversion rate to psychosis and changes in prodromal symptoms in a group of first-degree relatives of patients with schizophrenia and to compare the conversion rate in those with and without prodromal symptoms as assessed by the Structured Interview for Prodromal Syndromes (SIPS) and Scale of Prodromal Symptoms (SOPS). Method: Participants were the first-degree relatives of hospitalized patients with schizophrenia at Roozbeh Hospital, Tehran, Iran. At baseline, a trained psychiatrist interviewed the participants using the SIPS and the SOPS and assigned them to high- or low-risk groups either based on the presence of prodromal criteria or seeking mental health services. After 12 months, the same examiner re-evaluated the participants in order to determine the changes in their symptoms and identify the probable transitions to psychosis. Results: One hundred participants, 50 participants within each of high- or low-risk groups, were recruited at baseline. Eight participants dropped out of the study. At the follow-up, the rate of transition to full psychosis among high-risk group was 13 (95 CI 0.029, 0.23), whereas none of the low-risk participants developed psychosis. None of the high-risk participants demonstrated attenuation in their prodromal states after a one-year follow-up. In contrast, of the 50 low-risk participants, three experienced prodromal symptoms for psychosis during this period. High-risk participant's illustrated higher severity in almost all of the SOPS items compared to the low-risk participants at both baseline and follow-up evaluations. Conclusion: Prodromal syndrome for psychosis based on the SIPS and the SOPS was a predictive factor for transition to psychosis after a 12-month period in a group of first-degree relatives of patients with schizophrenia admitted to a psychiatric hospital in Iran. Conducting further studies on this at-risk population is highly recommended in order to provide practical methods for early screening and therapeutic interventions

The effects of quercetin on the gene expression of arginine metabolism key enzymes in human embryonic kidney 293 cells

Background: Arginine metabolism is an important factor involved in tumorigenesis, progression, and survival of tumor cells. Besides, other metabolites produced in the arginine metabolism process, such as polyamines, nitric oxide, argininosuccinate, and agmatine, play key roles in different stages of tumor development. On the other hand, herbal metabolites are widely used to treat cancer. One of these herbal flavonoids is quercetin. Methods: In this study, according to MTT assay data, two concentrations of quercetin flavonoid were selected (57.5 and 115 μM) to treat human embryonic kidney 293 (HEK293) cells. Then RNA was extracted from the cells and used as a template for cDNA synthesis. Using real-time PCR, the expression of key enzymes involved in arginine metabolism was evaluated, including arginase 2 (Arg2), ornithine carbamoyl transferase (OTC), agmatinase (AGMAT), arginase 1 (Arg1), nitric oxide synthase 1 (nNOS), arginine decarboxylase (ADC), ornithine decarboxylase 1 (ODC), ornithine carbamoyl transferase (OCT), spermidine synthase (SRM), spermine synthase (SMS), argininosuccinate synthase 1 (ASS1), and argininosuccinate lyase (ASL). The Student t-test was used to analyze the data considering a P value of < 0.05 as the significance level. Results: Our results indicated significant changes in the expression of arginine metabolism enzymes after quercetin exposure, confirming a role for quercetin plant flavonoid in regulating arginine metabolism in HEK293 cells. Conclusions: Quercetin could alter the gene expression of the key enzymes involved in arginine metabolism. This was the first study investigating the effects of quercetin on arginine metabolism in HEK293 cells. © 2021 The Authors

Antipsychotic drugs attenuate aberrant DNA methylation of DTNBP1 (dysbindin) promoter in saliva and post-mortem brain of patients with schizophrenia and Psychotic bipolar disorder

Due to the lack of genetic association between individual genes and schizophrenia (SCZ) pathogenesis, the current consensus is to consider both genetic and epigenetic alterations. Here, we report the examination of DNA methylation status of DTNBP1 promoter region, one of the most credible candidate genes affected in SCZ, assayed in saliva and post-mortem brain samples. The Illumina DNA methylation profiling and bisulfite sequencing of representative samples were used to identify methylation status of the DTNBP1 promoter region. Quantitative methylation specific PCR (qMSP) was employed to assess methylation of DTNBP1 promoter CpGs flanking a SP1 binding site in the saliva of SCZ patients, their first-degree relatives and control subjects (30, 15, and 30/group, respectively) as well as in post-mortem brains of patients with SCZ and bipolar disorder (BD) versus controls (35/group). qRT-PCR was used to assess DTNBP1 expression. We found DNA hypermethylation of DTNBP1 promoter in the saliva of SCZ patients (�12.5, P=0.036), particularly in drug-naïve patients (�20, P=0.011), and a trend toward hypermethylation in their first-degree relatives (P=0.085) versus controls. Analysis of post-mortem brain samples revealed an inverse correlation between DTNBP1 methylation and expression, and normalization of this epigenetic change by classic antipsychotic drugs. Additionally, BD patients with psychotic depression exhibited higher degree of methylation versus other BD patients (�80, P=0.025). DTNBP1 promoter DNA methylation may become a key element in a panel of biomarkers for diagnosis, prevention, or therapy in SCZ and at risk individuals pending confirmatory studies with larger sample sizes to attain a higher degree of significance. © 2015 Wiley Periodicals, Inc

Novel PTCH1 and concurrent TP53 mutations in four patients with numerous non-syndromic basal cell carcinomas: The paradigm of oncogenic synergy

There has been a significant increase in basal cell carcinoma (BCC) incidence, the most common cancer in humans and the age of presentation with the first diagnosis of BCC has decreased in past decades. In this study, we investigated the possibility of genetic markers that can lead to earlier and closer observation of patients at high risk for development of multiple BCCs. The overall goal is to decrease the morbidity and the economic burden of diagnosis and treatment of recurring and/or advanced BCCs. Four patients with numerous BCCs, some of them exceptionally large, were included in this study. A sample of representative BCCs, normal non–sun-exposed skin and blood samples were obtained from each patient. Whole-exome sequencing of DNA was conducted on all samples, and a series of bioinformatics filtering was performed to identify potentially pathogenic sequence variants. The analysis of the data resulted in detection of oncogenic mutations in PTCH1, two of which being novel, and concurrent mutations in TP53 in BCC tumours of all four patients. Such mutations may explain the numerous and postexcision recurring nature of the BCCs of exceptionally large size observed in all these patients, and they can be suggested to serve as a genetic marker for high-risk patients for early detection, prognostication and close follow-up

Inherited non-alcoholic fatty liver disease and dyslipidemia due to monoallelic ABHD5 mutations

Background &amp; Aims: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition and the most common liver disease worldwide, affecting more than one-third of the population. So far there have been no reports on mendelian inheritance in families with NAFLD. Methods: We performed whole-exome or targeted next-generation sequencing on patients with autosomal dominant NAFLD. Results: We report a heritable form of NAFLD and/or dyslipidemia due to monoallelic ABHD5 mutations, with complete clinical expression after the fourth decade of life, in 7 unrelated multiplex families encompassing 39 affected individuals. The prevalence of ABHD5-associated NAFLD was estimated to be 1 in 1,137 individuals in a normal population. Conclusion: We associate a Mendelian form of NAFLD and/or dyslipidemia with monoallelic ABHD5 mutations. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is a common multifactorial disorder with a strong genetic component. Inherited forms of NAFLD have been suspected but, their molecular pathogenesis has not been disclosed. Here we report a heritable form of NAFLD with clinical expression after 40 years of age, associated with monoallelic ABHD5 mutations