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Schizophrenia Epigenetics

Andrea Schmitt, Daniel Martins-de-Souza, Schahram Akbarian, Juliana S Cassoli, Hannelore Ehrenreich, Andre Fischer, Alfred Fonteh, Wagner F Gattaz, Michael Gawlik, Manfred Gerlach, Edna Grünblatt, Tobias Halene, Alkomiet Hasan, Kenij Hashimoto, Yong-Ku Kim, Sophie-Kathrin Kirchner, Johannes Kornhuber, Theo F J Kraus, Berend Malchow, Juliana M Nascimento, Moritz Rossner, Markus Schwarz, Johann Steiner, Leda Talib, Florence Thibaut, Peter Riederer, Peter Falkai
OBJECTIVES: Despite progress in identifying molecular pathophysiological processes in schizophrenia, valid biomarkers are lacking for both the disease and treatment response. METHODS: This comprehensive review summarises recent efforts to identify molecular mechanisms on the level of protein and gene expression and epigenetics, including DNA methylation, histone modifications and micro RNA expression. Furthermore, it summarises recent findings of alterations in lipid mediators and highlights inflammatory processes...
October 26, 2016: World Journal of Biological Psychiatry
Gavino Faa, Mirko Manchia, Roberta Pintus, Clara Gerosa, Maria Antonietta Marcialis, Vassilios Fanos
Starting from the Developmental Origins of Health and Disease (DOHaD) hypotheses proposed by David Barker, namely fetal programming, in the past years, there is a growing evidence of the major role played by epigenetic factors during the intrauterine life and the perinatal period. Furthermore, it has been assessed that these factors can affect the health status in infancy and even in adulthood. In this review, we focus our attention on the fetal programming of the brain, analyzing the most recent literature concerning the epigenetic factors that can influence the development of neuropsychiatric disorders such as bipolar disorders, major depressive disorders, and schizophrenia...
October 24, 2016: Birth Defects Research. Part C, Embryo Today: Reviews
Hilde de Kluiver, Jacobine E Buizer-Voskamp, Conor V Dolan, Dorret I Boomsma
We review the hypotheses concerning the association between the paternal age at childbearing and childhood psychiatric disorders (autism spectrum- and attention deficit/hyperactive disorder) and adult disorders (schizophrenia, bipolar-, obsessive-compulsive-, and major depressive disorder) based on epidemiological studies. Several hypotheses have been proposed to explain the paternal age effect. We discuss the four main-not mutually exclusive-hypotheses. These are the de novo mutation hypothesis, the hypothesis concerning epigenetic alterations, the selection into late fatherhood hypothesis, and the environmental resource hypothesis...
October 22, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Laura Whitton, Donna Cosgrove, Christopher Clarkson, Denise Harold, Kimberley Kendall, Alex Richards, Kiran Mantripragada, Michael J Owen, Michael C O'Donovan, James Walters, Annette Hartmann, Betina Konte, Dan Rujescu, Michael Gill, Aiden Corvin, Stephen Rea, Gary Donohoe, Derek W Morris
Epigenetic mechanisms are an important heritable and dynamic means of regulating various genomic functions, including gene expression, to orchestrate brain development, adult neurogenesis, and synaptic plasticity. These processes when perturbed are thought to contribute to schizophrenia pathophysiology. A core feature of schizophrenia is cognitive dysfunction. For genetic disorders where cognitive impairment is more severe such as intellectual disability, there are a disproportionally high number of genes involved in the epigenetic regulation of gene transcription...
October 20, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
J David Sweatt, Carol A Tamminga
This review concerns epigenetic mechanisms and their roles in conferring interindividual differences, especially as related to experientially acquired and genetically driven changes in central nervous system (CNS) function. In addition, the review contains commentary regarding the possible ways in which epigenomic changes may contribute to neuropsychiatric conditions and disorders and ways in which epigenotyping might be cross-correlated with clinical phenotyping in the context of precision medicine. The review begins with a basic description of epigenetic marking in the CNS and how these changes are powerful regulators of gene readout...
September 2016: Dialogues in Clinical Neuroscience
E Rizos, N Siafakas, E Skourti, C Papageorgiou, J Tsoporis, T H Parker, D I Christodoulou, D A Spandidos, E Katsantoni, V Zoumpourlis
Schizophrenia (SZ) and cancer (Ca) have a broad spectrum of clinical phenotypes and a complex biological background, implicating a large number of genetic and epigenetic factors. SZ is a chronic neurodevelopmental disorder signified by an increase in the expression of apoptotic molecular signals, whereas Ca is conversely characterized by an increase in appropriate molecular signaling that stimulates uncontrolled cell proliferation. The rather low risk of developing Ca in patients suffering from SZ is a hypothesis that is still under debate...
October 14, 2016: Molecular Medicine Reports
Raúl Alelú-Paz, Francisco J Carmona, José V Sanchez-Mut, Ariel Cariaga-Martínez, Ana González-Corpas, Nadia Ashour, Maria J Orea, Ana Escanilla, Alfonso Monje, Carmen Guerrero Márquez, Jerónimo Saiz-Ruiz, Manel Esteller, Santiago Ropero
Attempts to discover genes that are involved in the pathogenesis of major psychiatric disorders have been frustrating and often fruitless. Concern is building about the need to understand the complex ways in which nature and nurture interact to produce mental illness. We analyze the epigenome in several brain regions from schizophrenic patients with severe cognitive impairment using high-resolution (450K) DNA methylation array. We identified 139 differentially methylated CpG sites included in known and novel candidate genes sequences as well as in and intergenic sequences which functions remain unknown...
2016: Frontiers in Psychology
Sivan Subburaju, Andrew J Coleman, Miles G Cunningham, W Brad Ruzicka, Francine M Benes
GABAergic dysfunction in hippocampus, a key feature of schizophrenia (SZ), may contribute to cognitive impairment in this disorder. In stratum oriens (SO) of sector CA3/2 of the human hippocampus, a network of genes involved in the regulation of glutamic acid decarboxylase GAD67 has been identified. Several of the genes in this network including epigenetic factors histone deacetylase 1 (HDAC1) and death-associated protein 6 (DAXX), the GABAergic enzyme GAD65 as well as the kainate receptor (KAR) subunits GluR6 and 7 show significant changes in expression in this area in SZ...
October 12, 2016: Cerebral Cortex
Peilin Jia, Guangchun Han, Junfei Zhao, Pinyi Lu, Zhongming Zhao
SZGR 2.0 is a comprehensive resource of candidate variants and genes for schizophrenia, covering genetic, epigenetic, transcriptomic, translational and many other types of evidence. By systematic review and curation of multiple lines of evidence, we included almost all variants and genes that have ever been reported to be associated with schizophrenia. In particular, we collected ∼4200 common variants reported in genome-wide association studies, ∼1000 de novo mutations discovered by large-scale sequencing of family samples, 215 genes spanning rare and replication copy number variations, 99 genes overlapping with linkage regions, 240 differentially expressed genes, 4651 differentially methylated genes and 49 genes as antipsychotic drug targets...
October 12, 2016: Nucleic Acids Research
Jun Udagawa, Kodai Hino
Epidemiological studies suggest that exposure to prenatal stressors, including malnutrition, maternal immune activation (MIA), and adverse life events, is associated with increased risks of schizophrenia, autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD). However, the underlying pathophysiological mechanisms are unclear. The first trimester of pregnancy is particularly a vulnerable period. During this period, the self-renewal of neural stem cells and neurogenesis vigorously occur, and synaptic connections are partially formed in the telencephalon...
2016: Nihon Eiseigaku Zasshi. Japanese Journal of Hygiene
Luigi Attademo, Francesco Bernardini, Raffaele Garinella, Michael T Compton
Environmental pollution is a global problem with diverse and substantial public health implications. Although many environmental (i.e., non-genetic) risk factors for schizophrenia and other psychotic disorders have been identified, there has been comparatively little research on pollution as a possible risk factor. This is despite the fact that gene-by-environment interactions and epigenetic mechanisms are now recognized as likely facets of the etiology of schizophrenia, and the fact that pollution could potentially mediate the association between urban birth/upbringing and elevated risk...
October 5, 2016: Schizophrenia Research
M Hamza, S Halayem, R Mrad, S Bourgou, F Charfi, A Belhadj
BACKGROUND: The etiology of autism spectrum disorders (ASD) is complex and multifactorial, and the roles of genetic and environmental factors in its emergence have been well documented. Current research tends to indicate that these two factors act in a synergistic manner. The processes underlying this interaction are still poorly known, but epigenetic modifications could be the mediator in the gene/environment interface. The epigenetic mechanisms have been implicated in susceptibility to stress and also in the pathogenesis of psychiatric disorders including depression and schizophrenia...
September 27, 2016: L'Encéphale
Ana Popovic, Martin Bauer, Ulrich Sauerzopf, Lucie Bartova, Nicole Praschak-Rieder, Harald H Sitte, Siegfried Kasper, Matthäus Willeit
Sensitization is defined as a process whereby repeated intermittent exposure to a given stimulus results in an enhanced response at subsequent exposures. Next to robust findings of an increased dopamine synthesis capacity in schizophrenia, empirical data and neuroimaging studies support the notion that the mesolimbic dopamine system of patients with schizophrenia is more reactive compared to healthy controls. These studies led to the conceptualization of schizophrenia as a state of endogenous sensitization, as stronger behavioral response and increased dopamine release after amphetamine administration or exposure to stress have been observed in patients with schizophrenia...
September 9, 2016: International Journal of Neuropsychopharmacology
Seher Karsli-Ceppioglu
Preclinical Research Epigenetic mechanisms refer covalent modification of DNA and histone proteins that control transcriptional regulation of gene expression. Epigenetic regulation is involved in the development of the nervous system and plays an important role in the pathophysiology of psychiatric disorders, including depression, bipolar disorder, and schizophrenia. Epigenetic drugs, including histone deacetylation and DNA methylation inhibitors have received increased attention for the management of psychiatric diseases...
September 4, 2016: Drug Development Research
Eilis Hannon, Emma Dempster, Joana Viana, Joe Burrage, Adam R Smith, Ruby Macdonald, David St Clair, Colette Mustard, Gerome Breen, Sebastian Therman, Jaakko Kaprio, Timothea Toulopoulou, Hilleke E Hulshoff Pol, Marc M Bohlken, Rene S Kahn, Igor Nenadic, Christina M Hultman, Robin M Murray, David A Collier, Nick Bass, Hugh Gurling, Andrew McQuillin, Leonard Schalkwyk, Jonathan Mill
BACKGROUND: Schizophrenia is a highly heritable, neuropsychiatric disorder characterized by episodic psychosis and altered cognitive function. Despite success in identifying genetic variants associated with schizophrenia, there remains uncertainty about the causal genes involved in disease pathogenesis and how their function is regulated. RESULTS: We performed a multi-stage epigenome-wide association study, quantifying genome-wide patterns of DNA methylation in a total of 1714 individuals from three independent sample cohorts...
2016: Genome Biology
John Cromby, Emma Chung, Dimitris Papadopoulos, Chris Talbot
BACKGROUND: Epigenetic research in mental health has grown exponentially during the last decade and holds what some claim are "revolutionary" potentials for the development of new interdisciplinary models of mental ill health. Schizophrenia is the most appropriate diagnosis against which to assess progress in this regard. METHOD: Papers on epigenetics and schizophrenia identified in a systematic literature search are subject to a conceptually-driven narrative review that assesses the relations between schizophrenia and epigenetics; considers some issues associated with empirical studies; and thereby identifies key assumptions guiding this research...
August 25, 2016: Journal of Mental Health
Hsiao-Ying Wey, Tonya M Gilbert, Nicole R Zürcher, Angela She, Anisha Bhanot, Brendan D Taillon, Fredrick A Schroeder, Changing Wang, Stephen J Haggarty, Jacob M Hooker
Epigenetic dysfunction is implicated in many neurological and psychiatric diseases, including Alzheimer's disease and schizophrenia. Consequently, histone deacetylases (HDACs) are being aggressively pursued as therapeutic targets. However, a fundamental knowledge gap exists regarding the expression and distribution of HDACs in healthy individuals for comparison to disease states. Here, we report the first-in-human evaluation of neuroepigenetic regulation in vivo. Using positron emission tomography with [(11)C]Martinostat, an imaging probe selective for class I HDACs (isoforms 1, 2, and 3), we found that HDAC expression is higher in cortical gray matter than in white matter, with conserved regional distribution patterns within and between healthy individuals...
August 10, 2016: Science Translational Medicine
Lijuan Wang, Wei Jiang, Qing Lin, Yiyue Zhang, Cunyou Zhao
Single nucleotide polymorphisms (SNPs) in the human type A gamma-aminobutyric acid (GABA) receptor β2 subunit gene (GABRB2) have been associated with schizophrenia and quantitatively correlated with mRNA expression in the postmortem brain tissue of patients with schizophrenia. L-methionine (MET) administration has been reported to cause a recrudescence of psychotic symptoms in patients with schizophrenia, and similar symptoms have been generated in MET-induced mice. In this study, a zebrafish animal model was used to evaluate the relationship between the gabrb2 mRNA expression and its promoter DNA methylation in developmental and MET-induced schizophrenia-like zebrafish...
August 10, 2016: Genes, Brain, and Behavior
Rachel K Lanning, Clement C Zai, Daniel J Müller
Tardive dyskinesia (TD) is a serious and potentially irreversible side effect of long-term exposure to antipsychotic medication characterized by involuntary trunk, limb and orofacial muscle movements. Various mechanisms have been proposed for the etiopathophysiology of antipsychotic-induced TD in schizophrenia patients with genetic factors playing a prominent role. Earlier association studies have focused on polymorphisms in CYP2D6, dopamine-, serotonin-, GABA- and glutamate genes. This review highlights recent advances in the genetic investigation of TD...
August 2016: Pharmacogenomics
Yang-An Chuang, Tsung-Ming Hu, Chia-Hsiang Chen, Shih-Hsin Hsu, Hsin-Yao Tsai, Min-Chih Cheng
Activity-regulated cytoskeleton-associated protein (ARC), which interacts with the N-methyl-d-aspartate receptor (NMDAR) complex, is a critical effector molecule downstream of multiple neuronal signaling pathways. Dysregulation of the ARC/NMDAR complex can disrupt learning, memory, and normal brain functions. This study examined the role of ARC in susceptibility to schizophrenia. We used a resequencing strategy to identify the variants of ARC in 1078 subjects, including patients with schizophrenia and normal controls...
October 2016: Schizophrenia Research
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