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Schizophrenia Epigenetics

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https://www.readbyqxmd.com/read/28192769/disorganization-at-the-stage-of-schizophrenia-clinical-outcome-clinical-biological-study
#1
A Nestsiarovich, V Obyedkov, H Kandratsenka, M Siniauskaya, I Goloenko, N Waszkiewicz
BACKGROUND: According to the multidimensional model of schizophrenia, three basic psychopathological dimensions constitute its clinical structure: positive symptoms, negative symptoms and disorganization. The latter one is the newest and the least studied. Our aim was to discriminate disorganization in schizophrenia clinical picture and to identify its distinctive biological and socio-psychological particularities and associated genetic and environmental factors. METHODS: We used SAPS/SANS psychometrical scales, scales for the assessment of patient's compliance, insight, social functioning, life quality...
December 30, 2016: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28152499/contributions-of-polyunsaturated-fatty-acids-pufa-on-cerebral-neurobiology-an-integrated-omics-approach-with-epigenomic-focus
#2
Nabarun Chakraborty, Seid Muhie, Raina Kumar, Aarti Gautam, Seshamalini Srinivasan, Bintu Sowe, George Dimitrov, Stacy-Ann Miller, Marti Jett, Rasha Hammamieh
The epigenetic landscape is vulnerable to diets. Here, we investigated the influence of different polyunsaturated fatty acids (PUFA) dietary supplements on rodents' nervous system development and functions and potential consequences to neurodegenerative disorders. Our previous nutrigenomics study showed significant impact of high n-3 PUFA-enriched diet (ERD) on synaptogenesis and various neuromodulators. The present study introduced a second equicaloric diet with n-6 PUFA balanced by n-3 PUFA (BLD). The typical lab diet with high n-6 PUFA was the baseline...
January 5, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28140401/advanced-paternal-age-effects-in-neurodevelopmental-disorders-review-of-potential-underlying-mechanisms
#3
REVIEW
M Janecka, J Mill, M A Basson, A Goriely, H Spiers, A Reichenberg, L Schalkwyk, C Fernandes
Multiple epidemiological studies suggest a relationship between advanced paternal age (APA) at conception and adverse neurodevelopmental outcomes in offspring, particularly with regard to increased risk for autism and schizophrenia. Conclusive evidence about how age-related changes in paternal gametes, or age-independent behavioral traits affect neural development is still lacking. Recent evidence suggests that the origins of APA effects are likely to be multidimensional, involving both inherited predisposition and de novo events...
January 31, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28117656/epigenetic-profiling-of-human-brain-differential-dna-methylation-networks-in-schizophrenia
#4
Sheng-An Lee, Kuo-Chuan Huang
BACKGROUND: Epigenetics of schizophrenia provides important information on how the environmental factors affect the genetic architecture of the disease. DNA methylation plays a pivotal role in etiology for schizophrenia. Previous studies have focused mostly on the discovery of schizophrenia-associated SNPs or genetic variants. As postmortem brain samples became available, more and more recent studies surveyed transcriptomics of the diseases. In this study, we constructed protein-protein interaction (PPI) network using the disease associated SNP (or genetic variants), differentially expressed disease genes and differentially methylated disease genes (or promoters)...
December 5, 2016: BMC Medical Genomics
https://www.readbyqxmd.com/read/28115742/mef2c-transcription-factor-is-associated-with-the-genetic-and-epigenetic-risk-architecture-of-schizophrenia-and-improves-cognition-in-mice
#5
A C Mitchell, B Javidfar, V Pothula, D Ibi, E Y Shen, C J Peter, L K Bicks, T Fehr, Y Jiang, K J Brennand, R L Neve, J Gonzalez-Maeso, S Akbarian
Large-scale consortia mapping the genomic risk architectures of schizophrenia provide vast amounts of molecular information, with largely unexplored therapeutic potential. We harnessed publically available information from the Psychiatric Genomics Consortium, and report myocyte enhancer factor 2C (MEF2C) motif enrichment in sequences surrounding the top scoring single-nucleotide polymorphisms within risk loci contributing by individual small effect to disease heritability. Chromatin profiling at base-pair resolution in neuronal nucleosomes extracted from prefrontal cortex of 34 subjects, including 17 cases diagnosed with schizophrenia, revealed MEF2C motif enrichment within cis-regulatory sequences, including neuron-specific promoters and superenhancers, affected by histone H3K4 hypermethylation in disease cases...
January 24, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28095495/dna-methylation-analysis-of-brd1-promoter-regions-and-the-schizophrenia-rs138880-risk-allele
#6
Mads Dyrvig, Per Qvist, Jacek Lichota, Knud Larsen, Mette Nyegaard, Anders D Børglum, Jane H Christensen
The bromodomain containing 1 gene, BRD1 is essential for embryogenesis and CNS development. It encodes a protein that participates in histone modifying complexes and thereby regulates the expression of a large number of genes. Genetic variants in the BRD1 locus show association with schizophrenia and bipolar disorder and risk alleles in the promoter region correlate with reduced BRD1 expression. Insights into the transcriptional regulation of BRD1 and the pathogenic mechanisms associated with BRD1 risk variants, however, remain sparse...
2017: PloS One
https://www.readbyqxmd.com/read/28063323/genetic-and-epigenetic-regulation-on-the-transcription-of-gabrb2-genotype-dependent-hydroxymethylation-and-methylation-alterations-in-schizophrenia
#7
Lu Zong, Lin Zhou, Yu Hou, Lulu Zhang, Wei Jiang, Wenwei Zhang, Lijuan Wang, Xia Luo, Shiqing Wang, Cong Deng, Zhizhen Peng, Shufen Li, Jiming Hu, Hu Zhao, Cunyou Zhao
To improve our understanding of the abnormalities and non-Mendelian inheritance characteristics of schizophrenia, this study examined DNA methylation (5mC) and hydroxymethylation (5hmC) in the schizophrenia-associated GABRB2 gene encoding the type A γ-aminobutyric acid receptor β2 subunit. DNAs from the peripheral white blood cells of 279 schizophrenic patients and 256 controls from the Chinese Han population were examined to reveal that the GABRB2 promoter P1-5mC level which was correlated with olanzapine administration, P2-5mC/5hmC level, and Alu-5mC level which was correlated with administration of ziprasidone or oxcarbazepine, were increased in schizophrenic patients...
December 28, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28054990/mrna-expression-and-dna-methylation-analysis-of-serotonin-receptor-2a-htr2a-in-the-human-schizophrenic-brain
#8
Sern-Yih Cheah, Bruce R Lawford, Ross McD Young, Charles P Morris, Joanne Voisey
Serotonin receptor 2A (HTR2A) is an important signalling factor implicated in cognitive functions and known to be associated with schizophrenia. The biological significance of HTR2A in schizophrenia remains unclear as molecular analyses including genetic association, mRNA expression and methylation studies have reported inconsistent results. In this study, we examine HTR2A expression and methylation and the interaction with HTR2A polymorphisms to identify their biological significance in schizophrenia. Subjects included 25 schizophrenia and 25 control post-mortem brain samples...
January 4, 2017: Genes
https://www.readbyqxmd.com/read/28042663/all-our-sons-the-developmental-neurobiology-and-neuroendocrinology-of-boys-at-risk
#9
Allan N Schore
Why are boys at risk? To address this question, I use the perspective of regulation theory to offer a model of the deeper psychoneurobiological mechanisms that underlie the vulnerability of the developing male. The central thesis of this work dictates that significant gender differences are seen between male and female social and emotional functions in the earliest stages of development, and that these result from not only differences in sex hormones and social experiences but also in rates of male and female brain maturation, specifically in the early developing right brain...
January 2017: Infant Mental Health Journal
https://www.readbyqxmd.com/read/28011714/schizophrenia-associated-methylomic-variation-molecular-signatures-of-disease-and-polygenic-risk-burden-across-multiple-brain-regions
#10
Joana Viana, Eilis Hannon, Emma Dempster, Ruth Pidsley, Ruby Macdonald, Olivia Knox, Helen Spiers, Claire Troakes, Safa Al-Saraj, Gustavo Turecki, Leonard C Schalkwyk, Jonathan Mill
Genetic association studies provide evidence for a substantial polygenic component to schizophrenia, although the neurobiological mechanisms underlying the disorder remain largely undefined. Building on recent studies supporting a role for developmentally regulated epigenetic variation in the molecular etiology of schizophrenia, this study aimed to identify epigenetic variation associated with both a diagnosis of schizophrenia and elevated polygenic risk burden for the disease across multiple brain regions...
December 22, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27993603/the-neural-diathesis-stress-model-of-schizophrenia-revisited-an-update-on-recent-findings-considering-illness-stage-and-neurobiological-and-methodological-complexities
#11
REVIEW
Marita Pruessner, Alexis E Cullen, Monica Aas, Elaine F Walker
Over the past decade, our understanding of the role of stress in serious mental illness has become more sophisticated. In this paper, we revisit the neural diathesis-stress model of schizophrenia that was initially proposed in 1997 and updated in 2008. In light of cumulative research findings, we must now encompass evidence on the premorbid periods of psychosis, and our more nuanced understanding of hypothalamic-pituitary-adrenal (HPA) axis function and its association with neurodevelopmental, epigenetic, neurotransmitter, and inflammatory processes, as well as brain structure and function...
February 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27968732/genetics-of-schizophrenia-historical-insights-and-prevailing-evidence
#12
J van de Leemput, J L Hess, S J Glatt, M T Tsuang
Schizophrenia's (SZ's) heritability and familial transmission have been known for several decades; however, despite the clear evidence for a genetic component, it has been very difficult to pinpoint specific causative genes. Even so genetic studies have taught us a lot, even in the pregenomic era, about the molecular underpinnings and disease-relevant pathways. Recurring themes emerged revealing the involvement of neurodevelopmental processes, glutamate regulation, and immune system differential activation in SZ etiology...
2016: Advances in Genetics
https://www.readbyqxmd.com/read/27938391/false-data-positive-results-in-neurobiology-moving-beyond-the-epigenetics-of-blood-and-saliva-samples-in-mental-disorders
#13
EDITORIAL
A Cariaga-Martinez, R Alelú-Paz
Many psychiatric diseases are influenced by a set of several genetic and environmental factors that genetics alone cannot explain. Specifically, in schizophrenia and bipolar disorder the absence of consistently replicated genetic effects together with evidence for lasting changes in gene expression after environmental exposures suggest a role of epigenetic mechanisms in its pathophysiological mechanisms. In this field, the presence of positive results could potentially uncover molecular mechanisms of deregulated gene expression in these complex disorders...
December 12, 2016: Journal of Negative Results in Biomedicine
https://www.readbyqxmd.com/read/27931915/stratifying-empiric-risk-of-schizophrenia-among-first-degree-relatives-using-multiple-predictors-in-two-independent-indian-samples
#14
Triptish Bhatia, Elizabeth A Gettig, Irving I Gottesman, Jonathan Berliner, N N Mishra, Vishwajit L Nimgaonkar, Smita N Deshpande
BACKGROUND: Schizophrenia (SZ) has an estimated heritability of 64-88%, with the higher values based on twin studies. Conventionally, family history of psychosis is the best individual-level predictor of risk, but reliable risk estimates are unavailable for Indian populations. Genetic, environmental, and epigenetic factors are equally important and should be considered when predicting risk in 'at risk' individuals. OBJECTIVE: To estimate risk based on an Indian schizophrenia participant's family history combined with selected demographic factors...
December 2016: Asian Journal of Psychiatry
https://www.readbyqxmd.com/read/27886132/the-future-is-the-past-methylation-qtls-in-schizophrenia
#15
REVIEW
Anke Hoffmann, Michael Ziller, Dietmar Spengler
Genome-wide association studies (GWAS) have remarkably advanced insight into the genetic basis of schizophrenia (SCZ). Still, most of the functional variance in disease risk remains unexplained. Hence, there is a growing need to map genetic variability-to-genes-to-functions for understanding the pathophysiology of SCZ and the development of better treatments. Genetic variation can regulate various cellular functions including DNA methylation, an epigenetic mark with important roles in transcription and the mediation of environmental influences...
November 24, 2016: Genes
https://www.readbyqxmd.com/read/27872267/endophenotypes-epigenetics-polygenicity-and-more-irv-gottesman-s-dynamic-legacy
#16
David L Braff, Carol A Tamminga
First, we describe the hallmark contributions of Irv Gottesman's pioneering scholarship for schizophrenia research including concepts of polygenicity, gene × environment interactions, epigenetics and the endophenotype concept. Gottesman and colleagues' twin studies showed that genes, not social factors, mediate schizophrenia risk. He then showed that schizophrenia is highly polygenic. Next, he introduced the concept of epigenetics into schizophrenia research. Gottesman then introduced the quantitative endophenotype concept...
January 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/27857696/rethinking-schizophrenia-in-the-context-of-the-person-and-their-circumstances-seven-reasons
#17
Marino Pérez-Álvarez, José M García-Montes, Oscar Vallina-Fernández, Salvador Perona-Garcelán
We know a great deal about schizophrenia, but the current state of the art is one of uncertainty. Researchers are confused, and patients feel misunderstood. This situation has been identified as due largely to the fact that the dominant neurobiological perspective leaves out the person. The aim of the present article is to review and integrate a series of clinical, phenomenological, historical, cultural, epidemiological, developmental, epigenetic, and therapeutic phenomena in support of a suggestion that schizophrenia is above all a disorder of the person rather than of the brain...
2016: Frontiers in Psychology
https://www.readbyqxmd.com/read/27845777/newer-insights-into-the-role-of-mirna-a-tiny-genetic-tool-in-psychiatric-disorders-focus-on-post-traumatic-stress-disorder
#18
REVIEW
V V Giridharan, R A Thandavarayan, G R Fries, C Walss-Bass, T Barichello, N J Justice, M K Reddy, J Quevedo
Post-traumatic stress disorder (PTSD) is a mental disorder occurring in about 2-9% of individuals after their exposure to life-threatening events, such as severe accidents, sexual abuse, combat or a natural catastrophe. Because PTSD patients are exposed to trauma, it is likely that epigenetic modifications have an important role in disease development and prognosis. For the past two decades, abnormal expression of the epigenetic regulators microRNAs (miRs) and miR-mediated gene regulation have been given importance in a variety of human diseases, such as cancer, heart disease and viral infection...
November 15, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27818357/the-role-of-neuropathological-markers-in-the-interpretation-of-neuropsychiatric-disorders-focus-on-fetal-and-perinatal-programming
#19
REVIEW
Fanni Daniela, Gerosa Clara, Rais Monica, Ravarino Alberto, Van Eyken Peter, Fanos Vassilios, Faa Gavino
The study of neuropathological markers in patients affected by mental/psychiatric disorders is relevant for the comprehension of the pathogenesis and the correlation with the clinical symptomatology. The neuropathology of Alzheimer's disease (AD) recognizes intraneuronal and extracellular neurofibrillary formation responsible for neuronal degeneration. Immunohistochemical studies discovered many interesting results for a better interpretation of the AD pathogenesis, while the "metal hypothesis" supports that metal ions might differentially influence the formation of amyloid aggregates...
November 3, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27797829/genome-wide-transcriptional-profiling-and-structural-magnetic-resonance-imaging-in-the-maternal-immune-activation-model-of-neurodevelopmental-disorders
#20
Juliet Richetto, Robert Chesters, Annamaria Cattaneo, Marie A Labouesse, Ana Maria Carrillo Gutierrez, Tobias C Wood, Alessia Luoni, Urs Meyer, Anthony Vernon, Marco A Riva
Prenatal exposure to maternal infection increases the risk of neurodevelopmental disorders, including schizophrenia and autism. The molecular processes underlying this pathological association, however, are only partially understood. Here, we combined unbiased genome-wide transcriptional profiling with follow-up epigenetic analyses and structural magnetic resonance imaging to explore convergent molecular and neuromorphological alterations in corticostriatal areas of adult offspring exposed to prenatal immune activation...
October 23, 2016: Cerebral Cortex
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