Epigenetic mechanisms in schizophrenia

被引:1
作者
Akbarian, Schahram [1 ]
机构
[1] Icahn Sch Med Mt Sinai, Dept Psychiat, Friedman Brain Inst, New York, NY 10029 USA
基金
美国国家卫生研究院;
关键词
epigenome; DNA methylation; epigenetic drug target; histone modification; psychosis; prefrontal cortex;
D O I
暂无
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Schizophrenia is a major psychiatric disorder that lacks a unifying neuropathology, while currently available pharmacological treatments provide only limited benefits to many patients. This review will discuss how the field of neuroepigenetics could contribute to advancements of the existing knowledge on the neurobiology and treatment of psychosis. Genome-scale mapping of DNA methylation, histone modifications and variants, and chromosomal loopings for promoter-enhancer interactions and other epigenetic determinants of genome organization and function are likely to provide important clues about mechanisms contributing to dysregulated expression of synaptic and metabolic genes in schizophrenia brain, including the potential links to the underlying genetic risk architecture and environmental exposures. In addition, studies in animal models are providing a rapidly increasing list of chromatin-regulatory mechanisms with significant effects on cognition and complex behaviors, thereby pointing to the therapeutic potential of epigenetic drug targets in the nervous system. (C) 2014, AICH - Servier Research Group
引用
收藏
页码:405 / 417
页数:13
相关论文
共 148 条
[91]   Promoter-Wide Hypermethylation of the Ribosomal RNA Gene Promoter in the Suicide Brain [J].
McGowan, Patrick O. ;
Sasaki, Aya ;
Huang, Tony C. T. ;
Unterberger, Alexander ;
Suderman, Matthew ;
Ernst, Carl ;
Meaney, Michael J. ;
Turecki, Gustavo ;
Szyf, Moshe .
PLOS ONE, 2008, 3 (05)
[92]   Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse [J].
McGowan, Patrick O. ;
Sasaki, Aya ;
D'Alessio, Ana C. ;
Dymov, Sergiy ;
Labonte, Benoit ;
Szyf, Moshe ;
Turecki, Gustavo ;
Meaney, Michael J. .
NATURE NEUROSCIENCE, 2009, 12 (03) :342-348
[93]   Glutamate receptor expression in schizophrenic brain [J].
Meador-Woodruff, JH ;
Healy, DJ .
BRAIN RESEARCH REVIEWS, 2000, 31 (2-3) :288-294
[94]   Epigenetics and the Biological Definition of Gene x Environment Interactions [J].
Meaney, Michael J. .
CHILD DEVELOPMENT, 2010, 81 (01) :41-79
[95]   Gene expression profiling reveals alterations of specific metabolic pathways in schizophrenia [J].
Middleton, FA ;
Mirnics, K ;
Pierri, JN ;
Lewis, DA ;
Levitt, P .
JOURNAL OF NEUROSCIENCE, 2002, 22 (07) :2718-2729
[96]   Epigenomic profiling reveals DNA-Methylation changes associated with major psychosis [J].
Mill, Jonathan ;
Tang, Thomas ;
Kaminsky, Zachary ;
Khare, Tarang ;
Yazdanpanah, Simin ;
Bouchard, Luigi ;
Jia, Peixin ;
Assadzadeh, Abbas ;
Flanagan, James ;
Schumacher, Axel ;
Wang, Sun-Chong ;
Petronis, Arturas .
AMERICAN JOURNAL OF HUMAN GENETICS, 2008, 82 (03) :696-711
[97]   Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex [J].
Mirnics, K ;
Middleton, FA ;
Marquez, A ;
Lewis, DA ;
Levitt, P .
NEURON, 2000, 28 (01) :53-67
[98]   The Genome in Three Dimensions: A New Frontier in Human Brain Research [J].
Mitchell, Amanda C. ;
Bharadwaj, Rahul ;
Whittle, Catheryne ;
Krueger, Winfried ;
Mirnics, Karoly ;
Hurd, Yasmin ;
Rasmussen, Theodore ;
Akbarian, Schahram .
BIOLOGICAL PSYCHIATRY, 2014, 75 (12) :961-969
[99]   Loss of Histone Deacetylase 2 Improves Working Memory and Accelerates Extinction Learning [J].
Morris, Michael J. ;
Mahgoub, Melissa ;
Na, Elisa S. ;
Pranav, Heena ;
Monteggia, Lisa M. .
JOURNAL OF NEUROSCIENCE, 2013, 33 (15) :6401-6411
[100]   Reversal of Histone Methylation: Biochemical and Molecular Mechanisms of Histone Demethylases [J].
Mosammaparast, Nima ;
Shi, Yang .
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 79, 2010, 79 :155-179