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Schizophrenia Epigenetics

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https://www.readbyqxmd.com/read/29463818/changed-frontal-pole-gene-expression-suggest-altered-interplay-between-neurotransmitter-developmental-and-inflammatory-pathways-in-schizophrenia
#1
Elizabeth Scarr, Madhara Udawela, Brian Dean
Schizophrenia (Sz) probably occurs after genetically susceptible individuals encounter a deleterious environmental factor that triggers epigenetic mechanisms to change CNS gene expression. To determine if omnibus changes in CNS gene expression are present in Sz, we compared mRNA levels in the frontal pole (Brodmann's area (BA) 10), the dorsolateral prefrontal cortex (BA 9) and cingulate cortex (BA 33) from 15 subjects with Sz and 15 controls using the Affymetrix™ Human Exon 1.0 ST Array. Differences in mRNA levels (±≥20%; p < 0...
February 20, 2018: NPJ Schizophrenia
https://www.readbyqxmd.com/read/29448178/modification-of-the-association-between-antipsychotic-treatment-response-and-childhood-adversity-by-mmp9-gene-variants-in-a-first-episode-schizophrenia-cohort
#2
Nathaniel McGregor, Nicole Thompson, Kevin Sean O'Connell, Robin Emsley, Lize van der Merwe, Louise Warnich
Antipsychotics remain the most effective, and wide used option for ameliorating the symptoms of schizophrenia. However, inter-individual differences in treatment outcome are vast and suggest a role for genetic and environmental factors in affording favourable outcomes. A notable epigenetic relationship which has gained considerable traction in recent literature is the way in which the severity of childhood trauma can modify associations seen between genetic variation and antipsychotic treatment response. A potential mechanism of action which may facilitate this relationship is synaptic plasticity...
February 7, 2018: Psychiatry Research
https://www.readbyqxmd.com/read/29435496/zika-virus-alters-dna-methylation-of-neural-genes-in-an-organoid-model-of-the-developing-human-brain
#3
Sylvie Janssens, Michael Schotsaert, Rahul Karnik, Vinod Balasubramaniam, Marion Dejosez, Alexander Meissner, Adolfo García-Sastre, Thomas P Zwaka
Zika virus (ZIKV) infection during early pregnancy can cause microcephaly and associated defects at birth, but whether it can induce neurologic sequelae that appear later in life remains unclear. Using a model of the developing brain based on embryonic stem cell-derived brain organoids, we studied the impact of ZIKV infection on the DNA methylation pattern across the entire genome in selected neural cell types. The virus unexpectedly alters the DNA methylome of neural progenitors, astrocytes, and differentiated neurons at genes that have been implicated in the pathogenesis of a number of brain disorders, most prominently mental retardation and schizophrenia...
January 2018: MSystems
https://www.readbyqxmd.com/read/29430824/dna-methylation-analyses-of-the-candidate-genes-identified-by-a-methylome-wide-association-study-revealed-common-epigenetic-alterations-in-schizophrenia-and-bipolar-disorder
#4
Hiroko Sugawara, Yui Murata, Tempei Ikegame, Rie Sawamura, Shota Shimanaga, Yusuke Takeoka, Takeo Saito, Masashi Ikeda, Akane Yoshikawa, Fumichika Nishimura, Yoshiya Kawamura, Chihiro Kakiuchi, Tsukasa Sasaki, Nakao Iwata, Mamoru Hashimoto, Kiyoto Kasai, Tadafumi Kato, Miki Bundo, Kazuya Iwamoto
AIM: Schizophrenia (SZ) and bipolar disorder (BD) have been known to share genetic and environmental risk factors, and complex gene-environmental interactions may contribute to their pathophysiology. In contrast to high genetic overlap between SZ and BD, as revealed by genome-wide association studies, the extent of epigenetic overlap remains largely unknown. In the present study, we explore if SZ and BD share epigenetic risk factors in the same manner as they share genetic components...
February 11, 2018: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/29417943/inhibition-of-the-g9a-glp-histone-methyltransferase-complex-modulates-anxiety-related-behavior-in-mice
#5
Dong-Yao Wang, Joel Kosowan, James Samsom, Laura Leung, Kai-Lai Zhang, Ying-Xiang Li, Yan Xiong, Jian Jin, Arturas Petronis, Gabriel Oh, Albert H C Wong
Epigenetic gene-regulation abnormalities have been implicated in various neuropsychiatric disorders including schizophrenia and depression, as well as in the regulation of mood and anxiety. In addition, epigenetic mechanisms are involved in the actions of psychiatric drugs. Current anxiolytic drugs have significant shortcomings, and development of new medications is warranted. Two proteins, G9a (also known as EHMT2 or KMT1C) and GLP (G9a-like protein, also known as EHMT1 or KMT1D), which methylate lysine 9 of histone H3 (H3K9), could be promising anxiolytic targets...
February 8, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29383983/the-role-of-the-gut-microbiota-in-schizophrenia-current-and-future-perspectives
#6
Daniela Rodrigues-Amorim, Tania Rivera-Baltanás, Benito Regueiro, Carlos Spuch, María Elena de Las Heras, Raul Váquez-Noguerol Méndez, Maria Nieto-Araujo, C Barreiro-Villar, Jose M Olivares, Roberto C Agís-Balboa
OBJECTIVES: Schizophrenia is a poorly understood chronic disease. Its pathophysiology is complex, dynamic, and linked to epigenetic mechanisms and microbiota involvement. Nowadays, correlating schizophrenia with the environment makes sense owing, to its multidimensional implications: temporal and spatial variability. Microbiota involvement and epigenetic mechanisms are factors that are currently being considered to better understand another dimension of schizophrenia. METHODS: This review summarizes and discusses currently available information, focusing on the microbiota, epigenetic mechanisms, technological approaches aimed at performing exhaustive analyses of the microbiota, and psychotherapies, to establish future perspectives...
January 31, 2018: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/29382824/genetic-estimators-of-dna-methylation-provide-insights-into-the-molecular-basis-of-polygenic-traits
#7
Virginie Freytag, Vanja Vukojevic, Holger Wagner-Thelen, Annette Milnik, Christian Vogler, Markus Leber, Leonie Weinhold, Anne C Böhmer, Steffi Riedel-Heller, Wolfgang Maier, Dominique J-F de Quervain, Alfredo Ramirez, Andreas Papassotiropoulos
The large biological distance between genetic risk loci and their mechanistic consequences in the tissue of interest limits the ability to establish functionality of susceptibility variants for genetically complex traits. Such a biological gap may be reduced through the systematic study of molecular mediators of genomic action, such as epigenetic modification. Here, we report the identification of robust genetic estimators of whole-blood CpG methylation, which can serve as intermediate molecular traits amenable to association testing with other genetically complex traits...
January 31, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29364120/adaptive-sparse-multiple-canonical-correlation-analysis-with-application-to-imaging-epi-genomics-study-of-schizophrenia
#8
Wenxing Hu, Dongdong Lin, Shaolong Cao, Jingyu Liu, Jiayu Chen, Vince D Calhoun, Yu-Ping Wang
Finding correlations across multiple data sets in imaging and (epi)genomics is a common challenge. Sparse multiple canonical correlation analysis (SMCCA) is a multivariate model widely used to extract contributing features from each data while maximizing the cross-modality correlation. The model is achieved by using the combination of pairwise covariances between any two data sets. However, the scales of different pairwise covariances could be quite different and the direct combination of pairwise covariances in SMCCA is unfair...
February 2018: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/29357805/protein-c-reactive-as-biomarker-predictor-of-schizophrenia-phases-of-illness-a-systematic-review
#9
Laura Orsolini, Fabiola Sarchione, Federica Vellante, Michele Fornaro, Ilaria Matarazzo, Giovanni Martinotti, Alessandro Valchera, Marco Di Nicola, Alessandro Carano, Massimo Di Giannantonio, Giampaolo Perna, Luigi Olivieri, Domenico De Berardis
BACKGROUND: Schizophrenia is a complex illness in which genetic, environmental, and epigenetic components have been implicated. However, recently, psychiatric disorders appear to be related to a chronic inflammatory state, at the level of specific cerebral areas which have been found as well impaired and responsible of the schizophrenia symptomatology. Hence, a role of inflammatory mediators and cytokines has been as well supposed. Accordingly, it has been recently investigated the role of an acute inflammatory phase protein, the C-reactive protein (CRP)...
January 19, 2018: Current Neuropharmacology
https://www.readbyqxmd.com/read/29343074/understanding-the-influence-of-antipsychotic-drugs-on-global-methylation-events-and-its-relevance-in-treatment-response
#10
Babu Swathy, Koramannil R Saradalekshmi, Indu V Nair, Chandrasekharan Nair, Moinak Banerjee
AIM: The present study intends to evaluate whether antipsychotic drugs can modulate the host epigenome and if so whether drug-induced epigenetic modulation can explain the heterogeneity in drug response. METHODS: Present study was conducted in in vitro cells and significance of these in vitro observations was further evaluated in a clinical setting, between drug responsive and nonresponsive schizophrenia patients. A number of DNA modifications were assessed at global level using 5-methylcytosine, 5-hydroxymethylcytosine and 5-formylcytosine followed by evaluating the expression of epigenetic modifier genes and their crosstalk with miRNAs...
January 18, 2018: Epigenomics
https://www.readbyqxmd.com/read/29330379/identification-of-shared-genetic-variants-between-schizophrenia-and-lung-cancer
#11
Verena Zuber, Erik G Jönsson, Oleksandr Frei, Aree Witoelar, Wesley K Thompson, Andrew J Schork, Francesco Bettella, Yunpeng Wang, Srdjan Djurovic, Olav B Smeland, Ingrid Dieset, Ayman H Fanous, Rahul S Desikan, Sébastien Küry, Stéphane Bézieau, Anders M Dale, Ian G Mills, Ole A Andreassen
Epidemiology studies suggest associations between schizophrenia and cancer. However, the underlying genetic mechanisms are not well understood, and difficult to identify from epidemiological data. We investigated if there is a shared genetic architecture between schizophrenia and cancer, with the aim to identify specific overlapping genetic loci. First, we performed genome-wide enrichment analysis and second, we analyzed specific loci jointly associated with schizophrenia and cancer by the conjunction false discovery rate...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29302221/genetics-of-addictive-behavior-the-example-of-nicotine-dependence
#12
Philip Gorwood, Yann Le Strat, Nicolas Ramoz
The majority of addictive disorders have a significant heritability-roughly around 50%. Surprisingly, the most convincing association (a nicotinic acetylcholine receptor CHRNA5-A3-B4 gene cluster in nicotine dependence), with a unique attributable risk of 14%, was detected through a genome-wide association study (GWAS) on lung cancer, although lung cancer has a low heritability. We propose some explanations of this finding, potentially helping to understand how a GWAS strategy can be successful. Many endophenotypes were also assessed as potentially modulating the effect of nicotine, indirectly facilitating the development of nicotine dependence...
September 2017: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/29258399/perceived-racial-discrimination-and-dna-methylation-among-african-american-women-in-the-intergen-study
#13
Veronica Barcelona de Mendoza, Yunfeng Huang, Cindy A Crusto, Yan V Sun, Jacquelyn Y Taylor
INTRODUCTION: Experiences of racial discrimination have been associated with poor health outcomes. Little is known, however, about how perceived racial discrimination influences DNA methylation (DNAm) among African Americans (AAs). We examined the association of experiences of discrimination with DNAm among AA women in the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure (InterGEN) study. METHODS: The InterGEN study examines the effects of genetic and psychological factors on blood pressure among AA women and their children...
January 1, 2017: Biological Research for Nursing
https://www.readbyqxmd.com/read/29249816/novel-schizophrenia-risk-factor-pathways-regulate-fez1-to-advance-oligodendroglia-development
#14
REVIEW
Xianjun Chen, Li Ku, Ruyi Mei, Guanglu Liu, Chongchong Xu, Zhexing Wen, Xiaofeng Zhao, Fei Wang, Lan Xiao, Yue Feng
Neuropsychiatric disorders, represented by schizophrenia, affect not only neurons but also myelinating oligodendroglia (OL), both contribute to the complex etiology. Although numerous susceptibility genes for schizophrenia have been identified, their function has been primarily studied in neurons. Whether malfunction of risk genes underlies OL defects in schizophrenia pathogenesis remains poorly understood. In this study, we investigated the function and regulation of the well-recognized schizophrenia risk factor, Fasciculation and Elongation Protein Zeta-1 (FEZ1), in OL...
December 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29228394/the-psychiatric-risk-gene-transcription-factor-4-tcf4-regulates-neurodevelopmental-pathways-associated-with-schizophrenia-autism-and-intellectual-disability
#15
Marc P Forrest, Matthew J Hill, David H Kavanagh, Katherine E Tansey, Adrian J Waite, Derek J Blake
Background: Common genetic variants in and around the gene encoding transcription factor 4 (TCF4) are associated with an increased risk of schizophrenia. Conversely, rare damaging TCF4 mutations cause Pitt-Hopkins syndrome and have also been found in individuals with intellectual disability (ID) and autism spectrum disorder (ASD). Methods: Chromatin immunoprecipitation and next generation sequencing were used to identify the genomic targets of TCF4. These data were integrated with expression, epigenetic and disease gene sets using a range of computational tools...
December 8, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/29174863/adolescent-environmental-enrichment-prevents-the-emergence-of-schizophrenia-like-abnormalities-in-a-neurodevelopmental-model-of-schizophrenia
#16
Ewelina Bator, Joachim Latusz, Krzysztof Wędzony, Marzena Maćkowiak
In the present study, we investigated whether exposure to an enriched environment (EE) during adolescence might affect the behavioural dysfunction (sensorimotor gating deficit, memory and social interaction impairments) and neurochemical changes (GAD67 expression, histone methylation) induced by methylazoxymethanol (MAM) in the MAM-E17 rat model of schizophrenia. EE was introduced for 7 days in early adolescence (days 23-29), and behavioural and biochemical studies were performed on adult rats at postnatal day 70...
November 22, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29171493/-epigenetic-research-of-cognitive-deficit-in-schizophrenia-some-methodological-considerations
#17
T V Lezheiko, M V Alfimova
AIM: To highlights the problems of assessing cognitive deficits in schizophrenia, relevant to the epigenetic, as well as a wide range of other approaches to the search for biological bases of cognition. MATERIAL AND METHODS: The literature on the weaknesses in the evaluation of cognitive functions in patients with schizophrenia are summarized and discussed. The analysis is illustrated by our experience in developing a cognitive battery and a sample to examine relationships between DNA methylation in blood cells and cognitive deficits in schizophrenia...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29160620/dna-methylation-of-mb-comt-in-malaysian-schizophrenia-patients
#18
Abd Rahim Nour El Huda, Ku Zaifah Norsidah, Rahim Mohd Nabil Fikri, Mohd Noor Hanisah, Abdullah Kartini, A Talib Norlelawati
AIM: This study examined catechol-O-methyltransferase (COMT) DNA methylation in the peripheral blood of schizophrenia patients and also in healthy controls to investigate its potential use as a peripheral biomarker of schizophrenia and its relationships with the clinical variables of schizophrenia patients. METHODS: We examined the DNA methylation levels of COMT using genomic DNA from the peripheral blood of schizophrenia patients (n = 138) and healthy control participants (n = 132); all were Malaysian Malays...
November 21, 2017: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/29106556/location-matters-distinct-dna-methylation-patterns-in-gabaergic-interneuronal-populations-from-separate-microcircuits-within-the-human-hippocampus
#19
W Brad Ruzicka, Sivan Subburaju, Joseph T Coyle, Francine M Benes
Recent studies describe distinct DNA methylomes among phenotypic subclasses of neurons in the human brain, but variation in DNA methylation between common neuronal phenotypes distinguished by their function within distinct neural circuits remains an unexplored concept. Studies able to resolve epigenetic profiles at the level of microcircuits are needed to illuminate chromatin dynamics in the regulation of specific neuronal populations and circuits mediating normal and abnormal behaviors.The Illumina HumanMethylation450 BeadChip was used to assess genome-wide DNA methylation in stratum oriens GABAergic interneurons sampled by laser-microdissection from two discrete microcircuits along the trisynaptic pathway in postmortem human hippocampus from eight control, eight schizophrenia, and eight bipolar disorder subjects...
November 2, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29070826/genetic-insights-into-the-neurodevelopmental-origins-of-schizophrenia
#20
REVIEW
Rebecca Birnbaum, Daniel R Weinberger
Schizophrenia is a severe neuropsychiatric disorder with a longstanding history of neurobiological investigation. Although the underlying causal mechanisms remain unknown, early neurodevelopmental events have been implicated in pathogenesis, initially by epidemiological and circumstantial data but more recently by brain-specific molecular and genetic findings. Notably, genomic research has recently uncovered discrete risk variants and risk loci associated with schizophrenia, with the potential to elucidate disease mechanisms...
December 2017: Nature Reviews. Neuroscience
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