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Schizophrenia Epigenetics

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https://www.readbyqxmd.com/read/28523550/histone-posttranslational-modifications-in-schizophrenia
#1
Elizabeth A Thomas
Schizophrenia is a complex neuropsychiatric disorder with high heritability; however, family and twin studies have indicated that environmental factors also play important roles in the etiology of disease. Environmental triggers exert their influence on behavior via epigenetic mechanisms. Epigenetic modifications, such as histone acetylation and methylation, as well as DNA methylation, can induce lasting changes in gene expression and have therefore been implicated in promoting the behavioral and neuronal behaviors that characterize this disorder...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523549/dna-methylation-in-schizophrenia
#2
Lotta-Katrin Pries, Sinan Gülöksüz, Gunter Kenis
Schizophrenia is a highly heritable psychiatric condition that displays a complex phenotype. A multitude of genetic susceptibility loci have now been identified, but these fail to explain the high heritability estimates of schizophrenia. In addition, epidemiologically relevant environmental risk factors for schizophrenia may lead to permanent changes in brain function. In conjunction with genetic liability, these environmental risk factors-likely through epigenetic mechanisms-may give rise to schizophrenia, a clinical syndrome characterized by florid psychotic symptoms and moderate to severe cognitive impairment...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28521044/cross-tissue-exploration-of-genetic-and-epigenetic-effects-on-brain-gray-matter-in-schizophrenia
#3
Dongdong Lin, Jiayu Chen, Stefan Ehrlich, Juan R Bustillo, Nora Perrone-Bizzozero, Esther Walton, Vincent P Clark, Yu-Ping Wang, Jing Sui, Yuhui Du, Beng C Ho, Charles S Schulz, Vince D Calhoun, Jingyu Liu
Closely linking genetics and environment factors, epigenetics has been of increasing interest in psychiatric disease studies. In this work, we integrated single nucleotide polymorphisms (SNPs), DNA methylation of blood and saliva, and brain gray matter (GM) measures to explore the role of genetic and epigenetic variation to the brain structure changes in schizophrenia (SZ). By focusing on the reported SZ genetic risk regions, we applied a multi-stage multivariate analysis to a discovery dataset (92 SZ patients and 110 controls, blood) and an independent replication dataset (93 SZ patients and 99 controls, saliva)...
May 17, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28516910/genetic-architecture-of-epigenetic-and-neuronal-ageing-rates-in-human-brain-regions
#4
Ake T Lu, Eilis Hannon, Morgan E Levine, Eileen M Crimmins, Katie Lunnon, Jonathan Mill, Daniel H Geschwind, Steve Horvath
Identifying genes regulating the pace of epigenetic ageing represents a new frontier in genome-wide association studies (GWASs). Here using 1,796 brain samples from 1,163 individuals, we carry out a GWAS of two DNA methylation-based biomarkers of brain age: the epigenetic ageing rate and estimated proportion of neurons. Locus 17q11.2 is significantly associated (P=4.5 × 10(-9)) with the ageing rate across five brain regions and harbours a cis-expression quantitative trait locus for EFCAB5 (P=3.4 × 10(-20))...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28485403/gad1-alternative-transcripts-and-dna-methylation-in-human-prefrontal-cortex-and-hippocampus-in-brain-development-schizophrenia
#5
R Tao, K N Davis, C Li, J H Shin, Y Gao, A E Jaffe, M C Gondré-Lewis, D R Weinberger, J E Kleinman, T M Hyde
Genetic variations and adverse environmental events in utero or shortly after birth can lead to abnormal brain development and increased risk of schizophrenia. γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian brain, plays a vital role in normal brain development. GABA synthesis is controlled by enzymes derived from two glutamic acid decarboxylase (GAD) genes, GAD1 and GAD2, both of which produce transcript isoforms. While the full-length GAD1 transcript (GAD67) has been implicated in the neuropathology of schizophrenia, the transcript structure of GAD1 in the human brain has not been fully characterized...
May 9, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28480579/longitudinal-epigenetic-predictors-of-amygdala-hippocampus-volume-ratio
#6
Esther Walton, Charlotte A M Cecil, Matthew Suderman, Jingyu Liu, Jessica A Turner, Vince Calhoun, Stefan Ehrlich, Caroline L Relton, Edward D Barker
BACKGROUND: The ratio between amygdala:hippocampal (AH) volume has been associated with multiple psychiatric problems, including anxiety and aggression. Yet, little is known about its biological underpinnings. Here, we used a methylome-wide approach to test (a) whether DNA methylation in early life (birth, age 7) prospectively associates with total AH volume ratio in early adulthood, and (b) whether significant DNA methylation markers are influenced by prenatal risk factors. METHODS: Analyses were based on a subsample (n = 109 males) from the Avon Longitudinal Study of Parents and Children, which included measures of prenatal risk, DNA methylation (Infinium Illumina 450k), T1-weighted brain scans and psychopathology in early adulthood (age 18-21)...
May 8, 2017: Journal of Child Psychology and Psychiatry, and Allied Disciplines
https://www.readbyqxmd.com/read/28470099/understanding-epigenetics-of-schizophrenia-in-the-backdrop-of-its-antipsychotic-drug-therapy
#7
Babu Swathy, Moinak Banerjee
The diatheses of gene and environment interaction in schizophrenia (SCZ) are becoming increasingly evident. Genetic and epigenetic backgrounds are being considered in stratifying and addressing phenotypic variation and drug response in SCZ. But how much of these epigenetic alterations are the primary contributing factor, toward disease pathogenesis and drug response, needs further clarity. Evidence indicates that antipsychotic drugs can also alter the epigenetic homeostasis thereby inducing pharmacoepigenomic effects...
May 4, 2017: Epigenomics
https://www.readbyqxmd.com/read/28463237/epigenetic-and-transgenerational-mechanisms-in-infection-mediated-neurodevelopmental-disorders
#8
REVIEW
U Weber-Stadlbauer
Prenatal infection is an environmental risk factor for various brain disorders with neurodevelopmental components, including autism spectrum disorder and schizophrenia. Modeling this association in animals shows that maternal immune activation negatively affects fetal brain development and leads to the emergence of behavioral disturbances later in life. Recent discoveries in these preclinical models suggest that epigenetic modifications may be a critical molecular mechanism by which prenatal immune activation can mediate changes in brain development and functions, even across generations...
May 2, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28439515/endogenous-retroviruses-with-us-and-against-us
#9
REVIEW
Thomas J Meyer, Jimi L Rosenkrantz, Lucia Carbone, Shawn L Chavez
Mammalian genomes are scattered with thousands of copies of endogenous retroviruses (ERVs), mobile genetic elements that are relics of ancient retroviral infections. After inserting copies into the germ line of a host, most ERVs accumulate mutations that prevent the normal assembly of infectious viral particles, becoming trapped in host genomes and unable to leave to infect other cells. While most copies of ERVs are inactive, some are transcribed and encode the proteins needed to generate new insertions at novel loci...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/28406917/methylomic-changes-in-individuals-with-psychosis-prenatally-exposed-to-endocrine-disrupting-compounds-lessons-from-diethylstilbestrol
#10
COMPARATIVE STUDY
Fabrice Rivollier, Boris Chaumette, Narjes Bendjemaa, Mélanie Chayet, Bruno Millet, Nematollah Jaafari, Amina Barhdadi, Louis-Philippe Lemieux Perreault, Sylvie Provost, Marie-Pierre Dubé, Raphaël Gaillard, Marie-Odile Krebs, Oussama Kebir
BACKGROUND: In the Western world, between 1940 and 1970, more than 2 million people were exposed in utero to diethylstilbestrol (DES). In exposed individuals, and in their descendants, adverse outcomes have been linked to such exposure, including cancers, genital malformations, and less consistently, psychiatric disorders. We aimed to explore whether prenatal DES exposure would be associated with DNA methylation changes, and whether these epigenetic modifications would be associated with increased risk of psychosis...
2017: PloS One
https://www.readbyqxmd.com/read/28387726/rethinking-the-epigenetic-framework-to-unravel-the-molecular-pathology-of-schizophrenia
#11
REVIEW
Ariel Cariaga-Martinez, Raúl Alelú-Paz
Schizophrenia is a complex mental disorder whose causes are still far from being known. Although researchers have focused on genetic or environmental contributions to the disease, we still lack a scientific framework that joins molecular and clinical findings. Epigenetic can explain how environmental variables may affect gene expression without modifying the DNA sequence. In fact, neuroepigenomics represents an effort to unify the research available on the molecular pathology of mental diseases, which has been carried out through several approaches ranging from interrogating single DNA methylation events and hydroxymethylation patterns, to epigenome-wide association studies, as well as studying post-translational modifications of histones, or nucleosomal positioning...
April 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28372995/targeting-aggression-in-severe-mental-illness-the-predictive-role-of-genetic-epigenetic-and-metabolomic-markers
#12
REVIEW
Mirko Manchia, Vassilios Fanos
Human aggression is a complex and widespread social behavior that is overrepresented in individuals affected by severe mental illness (SMI), such as schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). A substantial proportion of the liability threshold for aggressive behavior is determined by genetic factors, and environmental moderators might precipitate the manifestation of this behavioral phenotype through modification of gene expression via the epigenetic machinery...
April 2, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28359301/bromodomain-protein-4-discriminates-tissue-specific-super-enhancers-containing-disease-specific-susceptibility-loci-in-prostate-and-breast-cancer
#13
Verena Zuber, Francesco Bettella, Aree Witoelar, Ole A Andreassen, Ian G Mills, Alfonso Urbanucci
BACKGROUND: Epigenetic information can be used to identify clinically relevant genomic variants single nucleotide polymorphisms (SNPs) of functional importance in cancer development. Super-enhancers are cell-specific DNA elements, acting to determine tissue or cell identity and driving tumor progression. Although previous approaches have been tried to explain risk associated with SNPs in regulatory DNA elements, so far epigenetic readers such as bromodomain containing protein 4 (BRD4) and super-enhancers have not been used to annotate SNPs...
March 31, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28358303/a-novel-bio-psychosocial-behavioral-treatment-model-in-schizophrenia
#14
REVIEW
Yong-Ku Kim, Joonho Choi, Seon-Cheol Park
Despite the substantial burden of illness in schizophrenia, there has been a discrepancy between the beneficial effects of an increased use of antipsychotic medications and achieving limited recovery or remission. Because the focus of the most common antipsychotic medications is on dopamine, which is associated with positive symptoms, there is an unmet need for patients with negative symptoms. Since cognitive and negative symptoms rather than positive symptoms are more closely associated with psychosocial impairments in patients with schizophrenia, the non-dopaminergic systems including glutamate and γ-aminobutyric acid (GABA) of the prefrontal cortex should be of concern as well...
March 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28335457/the-epigenetic-link-between-prenatal-adverse-environments-and-neurodevelopmental-disorders
#15
REVIEW
Marija Kundakovic, Ivana Jaric
Prenatal adverse environments, such as maternal stress, toxicological exposures, and viral infections, can disrupt normal brain development and contribute to neurodevelopmental disorders, including schizophrenia, depression, and autism. Increasing evidence shows that these short- and long-term effects of prenatal exposures on brain structure and function are mediated by epigenetic mechanisms. Animal studies demonstrate that prenatal exposure to stress, toxins, viral mimetics, and drugs induces lasting epigenetic changes in the brain, including genes encoding glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf)...
March 18, 2017: Genes
https://www.readbyqxmd.com/read/28300292/hdac1-and-hdac3-underlie-dynamic-h3k9-acetylation-during-embryonic-neurogenesis-and-in-schizophrenia-like-animals
#16
Josef Večeřa, Eva Bártová, Jana Krejčí, Soňa Legartová, Denisa Komůrková, Jana Rudá-Kučerová, Tibor Štark, Eva Dražanová, Tomáš Kašpárek, Alexandra Šulcová, Frank J Dekker, Wiktor Szymanski, Christian Seiser, Georg Weitzer, Raphael Mechoulam, Vincenzo Micale, Stanislav Kozubek
Although histone acetylation is one of the most widely studied epigenetic modifications, there is still a lack of information regarding how the acetylome is regulated during brain development and pathophysiological processes. We demonstrate that the embryonic brain (E15) is characterized by an increase in H3K9 acetylation as well as decreases in the levels of HDAC1 and HDAC3. Moreover, experimental induction of H3K9 hyperacetylation led to the overexpression of NCAM in the embryonic cortex and depletion of Sox2 in the subventricular ependyma, which mimicked the differentiation processes...
March 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28298276/early-life-nutritional-programming-of-cognition-the-fundamental-role-of-epigenetic-mechanisms-in-mediating-the-relation-between-early-life-environment-and-learning-and-memory-process
#17
REVIEW
Laura Moody, Hong Chen, Yuan-Xiang Pan
The perinatal period is a window of heightened plasticity that lays the groundwork for future anatomic, physiologic, and behavioral outcomes. During this time, maternal diet plays a pivotal role in the maturation of vital organs and the establishment of neuronal connections. However, when perinatal nutrition is either lacking in specific micro- and macronutrients or overloaded with excess calories, the consequences can be devastating and long lasting. The brain is particularly sensitive to perinatal insults, with several neurologic and psychiatric disorders having been linked to a poor in utero environment...
March 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28282074/-epigenetics-2-0-the-multiple-faces-of-the-genome
#18
Marcelo Rubinstein
Epigenetics is the branch of genetics that studies the dynamic relationship between stable genotypes and varying phenotypes. To this end, epigenetics aims to discover the molecular mechanisms that explain how different nutrients and hormones, environmental changes, and emotional, social and cognitive experiences modify gene expression and behaviors, even permanently so. Psychiatry has learned that diseases with strong genetic predisposition, such as schizophrenia, show a concordance of around 50% between monozygotic twins, thus evidencing the importance of the genetic background and the presence of environmental variables that stimulate or block phenotypic development...
September 2016: Vertex: Revista Argentina de Psiquiatriá
https://www.readbyqxmd.com/read/28269013/integration-of-snps-fmri-methylation-data-with-sparse-multi-cca-for-schizophrenia-study
#19
Wenxing Hu, Dongdong Lin, Vince D Calhoun, Yu-Ping Wang
Schizophrenia (SZ) is a complex mental disorder associated with genetic variations, brain development and activities, and environmental factors. There is an increasing interest in combining genetic, epigenetic and neuroimaging datasets to explore different level of biomarkers for the correlation and interaction between these diverse factors. Sparse Multi-Canonical Correlation Analysis (sMCCA) is a powerful tool that can analyze the correlation of three or more datasets. In this paper, we propose the sMCCA model for imaging genomics study...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28268598/predicting-schizophrenia-by-fusing-networks-from-snps-dna-methylation-and-fmri-data
#20
Su-Ping Deng, Dongdong Lin, Vince D Calhoun, Yu-Ping Wang
In order to comprehensively utilize complementary information from multiple types of data for better disease diagnosis, in this study, we applied a network fusion based approach to integrating three types of data including genetic, epigenetic and neuroimaging data from a study of schizophrenia patients (SCZ). A network is a map of interactions, which contributes to investigating the connectivity of components or links between sub-units. We exploited the potential of using networks as features for discriminating SCZ from healthy controls...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
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