Genetics and Epigenetics of Schizophrenia

Schizophrenia (SCZ) is a complex mental disorder, with a longstanding history of neurobiological investigation. It is more common in those persons who are genetically predisposed to the disorder. Since Kraepelin, psychiatrists were aware that the SCZ tended to run in families. Its heritability is up to 85%. Although the etiology of SCZ is unknown, it is now thought to be multifactorial, with multiple susceptibility genes interacting with environmental and developmental factors. There is a huge amount of genetic studies, including polymorphisms, expression, methylation, microRNAs, and epigenomics. However, identifying genes for SCZ using traditional genetic approaches has thus far proven quite difficult. Reasons for this include the complexity, heterogeneity, and comorbidity of this disorder, and also the poor definition of the clinical phenotype. Important approaches to find the relation between genotype and phenotype and may be causal genetic factors are endophenotypes and pathway analysis. However, genetic researchers need to consider carefully the models of causality they choose. There is a pathophysiological pathway that extends from genes, through proteins, neurons, neural circuits, neural regions, mental functions, external behaviors, and symptoms of SCZ. In this chapter, the genetics and epigenetics of SCZ are briefly discussed

The Role of Epigenetics in Psychosis

Epigenetics (genome - environment interaction) is the study of mitotically heritable, but reversible changes in gene expression without any change in DNA modifications and the chromatin structure. Transition to psychosis is a complex and longitudinal process during which epigenetic changes have been hypothesized and investigated. This process is especially important in individuals at high/ultrahigh risk for psychosis, before the development of full-blown psychosis. Psychoses is a range of complex disorders, where genetic variants explain only a portion of risk. Neuro-epigenetic mechanisms may explain the remaining share of risk, as well as the transition from susceptibility to the actual disease. There is a need for computational model of psychosis integrating genetic risk with environmental factors (epigenetic) associated with the disorder to discover its pathophysiological pathways. Epigenetic dysregulation of many genes has been widely speculated that are important factors involved in etiology, pathophysiology, and course of the psychoses, such as schizophrenia, and mood disorders with psychotic features. In addition, the role of epigenetic changes, including histone and DNA modifications and also targeting microRNAs in the treatment of psychoses is a new field of investigations

Evaluation of RANKL/OPG Serum Concentration Ratio as a New Biomarker for Coronary Artery Calcification: A Pilot Study

Objective. There is a strong need for biomarkers to identify patients at risk for future cardiovascular events related with progressive atherosclerotic disease. Osteoprotegerin (OPG) protects the skeleton from excessive bone resorption by binding to receptor activator of nuclear factor-κB ligand (RANKL) and preventing it from binding to its receptor, receptor activator of nuclear factor-κB. However, conflicting results have been obtained about association of serum level of OPG or RANKL with coronary artery disease (CAD). Based on their role in inflammation and matrix degradation and the fact that atherosclerotic plaque formation is an inflammatory process, we hypothesized that RANKL : OPG ratio could be a better biomarker for CAD. Methods. In this cross-sectional study, the correlation between RANKL : OPG ratio serum concentration and coronary artery calcification (CAC) in 50 patients with ischemic coronary disease has been investigated. We used ELISA method for measuring RANKL and OPG serum concentrations. Results. There was a significant correlation between RANKL : OPG serum concentration ratio and CAC in our study population (P = 0.01). Conclusion. Our results suggested that RANKL : OPG ratio concentration has a potential of being used as a marker for coronary artery disease

Raw driving data of passenger cars considering traffic conditions in Semnan city

This article analyzes raw driving data of passenger cars in the city of Semnan in Iran, with the objective of understanding the impact of traffic conditions at different times of day (morning, noon, evening, and night). For this study, two cars, the Toyota Prius and the Peugeot Pars (or the IKCO Persia), were used, and the data of speed, longitude, latitude, and altitude of the vehicles were acquired. This data was collected over a week (July 21–28, 2022) for a distance of 670 km (13 hr), with the help of the Global Positioning System application, and were presented for both cars. In addition to this, the data on fuel consumption and average speed, based on the Electronic Control Unit in the Prius, was also collected. Finally, a sensitivity analysis was done on the features of the raw data, based on the Principal Component Analysis method

Longitudinal Effects of Bumetanide on Neuro-Cognitive Functioning in Drug-Resistant Epilepsy

Antiepileptic drugs (AEDs) have repeatedly shown inconsistent and almost contradictory effects on the neurocognitive system, from substantial impairments in processing speed to the noticeable improvement in working memory and executive functioning. Previous studies have provided a novel insight into the cognitive improvement by bumetanide as a potential antiepileptic drug. Through the current investigation, we evaluated the longitudinal effects of bumetanide, an NKCC1 co-transporter antagonist, on the brain microstructural organization as a probable underlying component for cognitive performance. Microstructure assessment was completed using SPM for the whole brain assay and Freesurfer/TRACULA for the automatic probabilistic tractography analysis. Primary cognitive operations including selective attention and processing speed, working memory capacity and spatial memory were evaluated in 12 patients with a confirmed diagnosis of refractory epilepsy. Participants treated with bumetanide (2 mg/ day) in two divided doses as an adjuvant therapy to their regular AEDs for 6 months, which followed by the re-assessment of their cognitive functions and microstructural organizations. Seizure frequency reduced in eight patients which accompanied by white matter reconstruction; fractional anisotropy (FA) increased in the cingulum-cingulate gyrus (CCG), anterior thalamic radiation (ATR), and temporal part of the superior longitudinal fasciculus (SLFt) in correlation with the clinical response. The voxel-based analysis in responder patients revealed increased FA in the left hippocampus, right cerebellum, and right medial temporal lobe, while mean diffusivity (MD) values reduced in the right occipital lobe and cerebellum. Microstructural changes in SLFt and ATR accompanied by a reduction in the error rate in the spatial memory test. These primary results have provided preliminary evidence for the effect of bumetanide on cognitive functioning through microstructural changes in patients with drug-resistant epilepsy

Iranian joint registry (iranian national hip and knee arthroplasty registry)

Periodic evaluation and monitoring the health and economic outcome of joint replacement surgery is a common and popular process under the territory of joint registries in many countries. In this article we introduce the methodology used for the foundation of the National Iranian Joint Registry (IJR) with a joint collaboration of the Social Security Organization (SSO) and academic research departments considering the requirements of the Iran's Ministry of Health and Education. ©BY THE ARCHIVES OF BONE AND JOINT SURGERY

Iranian joint registry (iranian national hip and knee arthroplasty registry)

Periodic evaluation and monitoring the health and economic outcome of joint replacement surgery is a common and popular process under the territory of joint registries in many countries. In this article we introduce the methodology used for the foundation of the National Iranian Joint Registry (IJR) with a joint collaboration of the Social Security Organization (SSO) and academic research departments considering the requirements of the Iran's Ministry of Health and Education. ©BY THE ARCHIVES OF BONE AND JOINT SURGERY