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Epigenetics of Schizophrenia

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Behavioral Neurobiology of Schizophrenia and Its Treatment

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 4))

Abstract

Epigenetic regulators of gene expression including DNA cytosine methylation and posttranslational histone modifications could play a role for some of the molecular alterations associated with schizophrenia. For example, in prefrontal cortex of subjects with schizophrenia, abnormal DNA or histone methylation at sites of specific genes and promoters is associated with changes in RNA expression. These findings are of interest from a neurodevelopmental perspective because there is increasing evidence that epigenetic markings for a substantial portion of genes and loci are highly regulated during the first years of life. Furthermore, there is circumstantial evidence that a subset of antipsychotic drugs, including the atypical, Clozapine, interfere with chromatin remodeling mechanisms. Challenges for the field include (1) no clear consensus yet regarding disease-associated changes, (2) the lack of cell-specific chromatin assays which makes it difficult to ascribe epigenetic alterations to specific cell populations, and (3) lack of knowledge about the stability or turnover of epigenetic markings at specific loci in (brain) chromatin. Despite these shortcomings, the study of DNA and histone modifications in chromatin extracted from diseased and control brain tissue is likely to provide valuable insight into the genomic risk architecture of schizophrenia, particularly in the large majority of cases for which a straightforward genetic cause still remains elusive.

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References

  • Abdolmaleky HM, Cheng KH, Russo A, Smith CL, Faraone SV, Wilcox M, Shafa R, Glatt SJ, Nguyen G, Ponte JF, Thiagalingam S, Tsuang MT (2005a) Hypermethylation of the reelin (RELN) promoter in the brain of schizophrenic patients: a preliminary report. Am J Med Genet B Neuropsychiatr Genet 134:60–66

    Google Scholar 

  • Abdolmaleky HM, Thiagalingam S, Wilcox M (2005b) Genetics and epigenetics in major psychiatric disorders: dilemmas, achievements, applications, and future scope. Am J Pharmacogenomics 5:149–160

    PubMed  CAS  Google Scholar 

  • Abdolmaleky HM, Cheng KH, Faraone SV, Wilcox M, Glatt SJ, Gao F, Smith CL, Shafa R, Aeali B, Carnevale J, Pan H, Papageorgis P, Ponte JF, Sivaraman V, Tsuang MT, Thiagalingam S (2006) Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder. Hum Mol Genet 15:3132–3145

    PubMed  CAS  Google Scholar 

  • Abel T, Zukin RS (2008) Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. Curr Opin Pharmacol 8:57–64

    PubMed  CAS  Google Scholar 

  • Akbarian S, Huang HS (2009) Epigenetic regulation in human brain-focus on histone lysine methylation. Biol Psychiatry 65:198–203

    PubMed  CAS  Google Scholar 

  • Akbarian S, Ruehl MG, Bliven E, Luiz LA, Peranelli AC, Baker SP, Roberts RC, Bunney WE Jr, Conley RC, Jones EG, Tamminga CA, Guo Y (2005) Chromatin alterations associated with down-regulated metabolic gene expression in the prefrontal cortex of subjects with schizophrenia. Arch Gen Psychiatry 62:829–840

    PubMed  CAS  Google Scholar 

  • Alarcon JM, Malleret G, Touzani K, Vronskaya S, Ishii S, Kandel ER, Barco A (2004) Chromatin acetylation, memory, and LTP are impaired in CBP+/− mice: a model for the cognitive deficit in Rubinstein–Taybi syndrome and its amelioration. Neuron 42:947–959

    PubMed  CAS  Google Scholar 

  • Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K (2007) High-resolution profiling of histone methylations in the human genome. Cell 129:823–837

    PubMed  CAS  Google Scholar 

  • Benes FM, Lim B, Matzilevich D, Subburaju S, Walsh JP (2008) Circuitry-based gene expression profiles in GABA cells of the trisynaptic pathway in schizophrenics versus bipolars. Proc Natl Acad Sci USA 105:20935–20940

    PubMed  CAS  Google Scholar 

  • Berger SL (2002) Histone modifications in transcriptional regulation. Curr Opin Genet Dev 12:142–148

    PubMed  CAS  Google Scholar 

  • Berger SL (2007) The complex language of chromatin regulation during transcription. Nature 447:407–412

    PubMed  CAS  Google Scholar 

  • Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A (2009) An operational definition of epigenetics. Genes Dev 23:781–783

    PubMed  CAS  Google Scholar 

  • Bertolino A, Blasi G (2009) The genetics of Schizophrenia. Neuroscience 164:288–299

    PubMed  CAS  Google Scholar 

  • Bollati V, Baccarelli A, Hou L, Bonzini M, Fustinoni S, Cavallo D, Byun HM, Jiang J, Marinelli B, Pesatori AC, Bertazzi PA, Yang AS (2007) Changes in DNA methylation patterns in subjects exposed to low-dose benzene. Cancer Res 67:876–880

    PubMed  CAS  Google Scholar 

  • Bozon B, Kelly A, Josselyn SA, Silva AJ, Davis S, Laroche S (2003) MAPK, CREB and zif268 are all required for the consolidation of recognition memory. Philos Trans R Soc Lond B Biol Sci 358:805–814

    PubMed  CAS  Google Scholar 

  • Browning JL, Patel T, Brandt PC, Young KA, Holcomb LA, Hicks PB (2005) Clozapine and the mitogen-activated protein kinase signal transduction pathway: implications for antipsychotic actions. Biol Psychiatry 57:617–623

    PubMed  CAS  Google Scholar 

  • Bullock WM, Cardon K, Bustillo J, Roberts RC, Perrone-Bizzozero NI (2008) Altered expression of genes involved in GABAergic transmission and neuromodulation of granule cell activity in the cerebellum of schizophrenia patients. Am J Psychiatry 165:1594–1603

    PubMed  Google Scholar 

  • Cheng MC, Liao DL, Hsiung CA, Chen CY, Liao YC, Chen CH (2008) Chronic treatment with aripiprazole induces differential gene expression in the rat frontal cortex. Int J Neuropsychopharmacol 11:207–216

    PubMed  CAS  Google Scholar 

  • Colvis CM, Pollock JD, Goodman RH, Impey S, Dunn J, Mandel G, Champagne FA, Mayford M, Korzus E, Kumar A, Renthal W, Theobald DE, Nestler EJ (2005) Epigenetic mechanisms and gene networks in the nervous system. J Neurosci 25:10379–10389

    PubMed  CAS  Google Scholar 

  • Connor CM, Akbarian S (2008) DNA methylation changes in schizophrenia and bipolar disorder. Epigenetics 3:55–58

    PubMed  Google Scholar 

  • Costa E, Chen Y, Dong E, Grayson DR, Kundakovic M, Maloku E, Ruzicka W, Satta R, Veldic M, Zhubi A, Guidotti A (2009) GABAergic promoter hypermethylation as a model to study the neurochemistry of schizophrenia vulnerability. Expert Rev Neurother 9:87–98

    PubMed  CAS  Google Scholar 

  • Craddock N, Owen MJ (2007) Rethinking psychosis: the disadvantages of a dichotomous classification now outweigh the advantages. World Psychiatry 6:84–91

    PubMed  Google Scholar 

  • Davis KL, Haroutunian V (2003) Global expression-profiling studies and oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet 362:758

    PubMed  Google Scholar 

  • Delisi LE (2009) Searching for the true genetic vulnerability for schizophrenia. Genome Med 1:14

    PubMed  Google Scholar 

  • Desaulniers D, Xiao GH, Leingartner K, Chu I, Musicki B, Tsang BK (2005) Comparisons of brain, uterus, and liver mRNA expression for cytochrome p450s, DNA methyltransferase-1, and catechol-o-methyltransferase in prepubertal female Sprague–Dawley rats exposed to a mixture of aryl hydrocarbon receptor agonists. Toxicol Sci 86:175–184

    PubMed  CAS  Google Scholar 

  • Dong E, Nelson M, Grayson DR, Costa E, Guidotti A (2008) Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation. Proc Natl Acad Sci USA 105:13614–13619

    PubMed  CAS  Google Scholar 

  • Dracheva S, Elhakem SL, McGurk SR, Davis KL, Haroutunian V (2004) GAD67 and GAD65 mRNA and protein expression in cerebrocortical regions of elderly patients with schizophrenia. J Neurosci Res 76:581–592

    PubMed  CAS  Google Scholar 

  • Endres M, Meisel A, Biniszkiewicz D, Namura S, Prass K, Ruscher K, Lipski A, Jaenisch R, Moskowitz MA, Dirnagl U (2000) DNA methyltransferase contributes to delayed ischemic brain injury. J Neurosci 20:3175–3181

    PubMed  CAS  Google Scholar 

  • Fatemi SH (2005) Reelin glycoprotein in autism and schizophrenia. Int Rev Neurobiol 71:179–187

    PubMed  CAS  Google Scholar 

  • Fatemi SH, Stary JM, Earle JA, Araghi-Niknam M, Eagan E (2005) GABAergic dysfunction in schizophrenia and mood disorders as reflected by decreased levels of glutamic acid decarboxylase 65 and 67 kDa and Reelin proteins in cerebellum. Schizophr Res 72:109–122

    PubMed  Google Scholar 

  • Feinberg AP (2007) Phenotypic plasticity and the epigenetics of human disease. Nature 447:433–440

    PubMed  CAS  Google Scholar 

  • Felsenfeld G, Groudine M (2003) Controlling the double helix. Nature 421:448–453

    PubMed  Google Scholar 

  • Fischle W, Wang Y, Allis CD (2003) Histone and chromatin cross-talk. Curr Opin Cell Biol 15:172–183

    PubMed  CAS  Google Scholar 

  • Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 102:10604–10609

    PubMed  CAS  Google Scholar 

  • Fuks F (2005) DNA methylation and histone modifications: teaming up to silence genes. Curr Opin Genet Dev 15:490–495

    PubMed  CAS  Google Scholar 

  • Gavin DP, Kartan S, Chase K, Jayaraman S, Sharma RP (2009) Histone deacetylase inhibitors and candidate gene expression: an in vivo and in vitro approach to studying chromatin remodeling in a clinical population. J Psychiatr Res 43:870–876

    PubMed  Google Scholar 

  • Grayson DR, Jia X, Chen Y, Sharma RP, Mitchell CP, Guidotti A, Costa E (2005) Reelin promoter hypermethylation in schizophrenia. Proc Natl Acad Sci USA 102:9341–9346

    PubMed  CAS  Google Scholar 

  • Grayson DR, Chen Y, Dong E, Kundakovic M, Guidotti A (2009) From trans-methylation to cytosine methylation: evolution of the methylation hypothesis of schizophrenia. Epigenetics 4:144–149

    PubMed  CAS  Google Scholar 

  • Guan Z, Giustetto M, Lomvardas S, Kim JH, Miniaci MC, Schwartz JH, Thanos D, Kandel ER (2002) Integration of long-term-memory-related synaptic plasticity involves bidirectional regulation of gene expression and chromatin structure. Cell 111:483–493

    PubMed  CAS  Google Scholar 

  • Guidotti A, Auta J, Davis JM, Di-Giorgi-Gerevini V, Dwivedi Y, Grayson DR, Impagnatiello F, Pandey G, Pesold C, Sharma R, Uzunov D, Costa E (2000) Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study. Arch Gen Psychiatry 57:1061–1069

    PubMed  CAS  Google Scholar 

  • Guidotti A, Dong E, Kundakovic M, Satta R, Grayson DR, Costa E (2009) Characterization of the action of antipsychotic subtypes on valproate-induced chromatin remodeling. Trends Pharmacol Sci 30:55–60

    PubMed  CAS  Google Scholar 

  • Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458:223–227

    PubMed  CAS  Google Scholar 

  • Hajkova P, Erhardt S, Lane N, Haaf T, El-Maarri O, Reik W, Walter J, Surani MA (2002) Epigenetic reprogramming in mouse primordial germ cells. Mech Dev 117:15–23

    PubMed  CAS  Google Scholar 

  • Hashimoto T, Bazmi HH, Mirnics K, Wu Q, Sampson AR, Lewis DA (2008) Conserved regional patterns of GABA-related transcript expression in the neocortex of subjects with schizophrenia. Am J Psychiatry 165:479–489

    PubMed  Google Scholar 

  • Hayes JJ, Hansen JC (2001) Nucleosomes and the chromatin fiber. Curr Opin Genet Dev 11:124–129

    PubMed  CAS  Google Scholar 

  • Hof PR, Haroutunian V, Copland C, Davis KL, Buxbaum JD (2002) Molecular and cellular evidence for an oligodendrocyte abnormality in schizophrenia. Neurochem Res 27:1193–1200

    PubMed  CAS  Google Scholar 

  • Huang HS, Akbarian S (2007) GAD1 mRNA expression and DNA methylation in prefrontal cortex of subjects with schizophrenia. PLoS ONE 2:e809

    PubMed  Google Scholar 

  • Huang HS, Matevossian A, Jiang Y, Akbarian S (2006) Chromatin immunoprecipitation in postmortem brain. J Neurosci Methods 156:284–292

    PubMed  CAS  Google Scholar 

  • Huang HS, Matevossian A, Whittle C, Kim SY, Schumacher A, Baker SP, Akbarian S (2007) Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters. J Neurosci 27:11254–11262

    PubMed  CAS  Google Scholar 

  • Iizuka M, Smith MM (2003) Functional consequences of histone modifications. Curr Opin Genet Dev 13:154–160

    PubMed  CAS  Google Scholar 

  • Iwamoto K, Bundo M, Yamada K, Takao H, Iwayama-Shigeno Y, Yoshikawa T, Kato T (2005) DNA methylation status of SOX10 correlates with its downregulation and oligodendrocyte dysfunction in schizophrenia. J Neurosci 25:5376–5381

    PubMed  CAS  Google Scholar 

  • Jablonka E, Lamb MJ (2002) The changing concept of epigenetics. Ann NY Acad Sci 981:82–96

    PubMed  Google Scholar 

  • Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080

    PubMed  CAS  Google Scholar 

  • Jiang Y, Langley B, Lubin FD, Renthal W, Wood MA, Yasui DH, Kumar A, Nestler EJ, Akbarian S, Beckel-Mitchener AC (2008a) Epigenetics in the nervous system. J Neurosci 28:11753–11759

    PubMed  CAS  Google Scholar 

  • Jiang Y, Matevossian A, Huang HS, Straubhaar J, Akbarian S (2008b) Isolation of neuronal chromatin from brain tissue. BMC Neurosci 9:42

    PubMed  Google Scholar 

  • Kaminsky Z, Wang SC, Petronis A (2006) Complex disease, gender and epigenetics. Ann Med 38:530–544

    PubMed  CAS  Google Scholar 

  • Kaminsky ZA, Tang T, Wang SC, Ptak C, Oh GH, Wong AH, Feldcamp LA, Virtanen C, Halfvarson J, Tysk C, McRae AF, Visscher PM, Montgomery GW, Gottesman II, Martin NG, Petronis A (2009) DNA methylation profiles in monozygotic and dizygotic twins. Nat Genet 41:240–245

    PubMed  CAS  Google Scholar 

  • Kharchenko PV, Tolstorukov MY, Park PJ (2008) Design and analysis of ChIP-seq experiments for DNA-binding proteins. Nat Biotechnol 26:1351–1359

    PubMed  CAS  Google Scholar 

  • Klose RJ, Bird AP (2006) Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci 31:89–97

    PubMed  CAS  Google Scholar 

  • Klose RJ, Zhang Y (2007) Regulation of histone methylation by demethylimination and demethylation. Nat Rev Mol Cell Biol 8:307–318

    PubMed  CAS  Google Scholar 

  • Klose RJ, Gardner KE, Liang G, Erdjument-Bromage H, Tempst P, Zhang Y (2007) Demethylation of histone H3K36 and H3K9 by Rph1: a vestige of an H3K9 methylation system in Saccharomyces cerevisiae? Mol Cell Biol 27:3951–3961

    PubMed  CAS  Google Scholar 

  • Korzus E, Rosenfeld MG, Mayford M (2004) CBP histone acetyltransferase activity is a critical component of memory consolidation. Neuron 42:961–972

    PubMed  CAS  Google Scholar 

  • Kouzarides T (2002) Histone methylation in transcriptional control. Curr Opin Genet Dev 12:198–209

    PubMed  CAS  Google Scholar 

  • Kristiansen LV, Huerta I, Beneyto M, Meador-Woodruff JH (2007) NMDA receptors and schizophrenia. Curr Opin Pharmacol 7:48–55

    PubMed  CAS  Google Scholar 

  • Kumar A, Choi KH, Renthal W, Tsankova NM, Theobald DE, Truong HT, Russo SJ, Laplant Q, Sasaki TS, Whistler KN, Neve RL, Self DW, Nestler EJ (2005) Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron 48:303–314

    PubMed  CAS  Google Scholar 

  • Kundakovic M, Chen Y, Costa E, Grayson DR (2007) DNA methyltransferase inhibitors coordinately induce expression of the human reelin and glutamic acid decarboxylase 67 genes. Mol Pharmacol 71:644–653

    PubMed  CAS  Google Scholar 

  • Levenson JM, Sweatt JD (2005) Epigenetic mechanisms in memory formation. Nat Rev Neurosci 6:108–118

    PubMed  CAS  Google Scholar 

  • Levenson JM, Roth TL, Lubin FD, Miller CA, Huang IC, Desai P, Malone LM, Sweatt JD (2006) Evidence that DNA (cytosine-5) methyltransferase regulates synaptic plasticity in the hippocampus. J Biol Chem 281:15763–15773

    PubMed  CAS  Google Scholar 

  • Levine AA, Guan Z, Barco A, Xu S, Kandel ER, Schwartz JH (2005) CREB-binding protein controls response to cocaine by acetylating histones at the fosB promoter in the mouse striatum. Proc Natl Acad Sci USA 102:19186–19191

    PubMed  CAS  Google Scholar 

  • Li J, Guo Y, Schroeder FA, Youngs RM, Schmidt TW, Ferris C, Konradi C, Akbarian S (2004) Dopamine D2-like antagonists induce chromatin remodeling in striatal neurons through cyclic AMP-protein kinase A and NMDA receptor signaling. J Neurochem 90:1117–1131

    PubMed  CAS  Google Scholar 

  • Lupski JR (2008) Schizophrenia: incriminating genomic evidence. Nature 455:178–179

    PubMed  CAS  Google Scholar 

  • Ma DK, Jang MH, Guo JU, Kitabatake Y, Chang ML, Pow-Anpongkul N, Flavell RA, Lu B, Ming GL, Song H (2009) Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science 323:1074–1077

    PubMed  CAS  Google Scholar 

  • Martin KC, Sun YE (2004) To learn better, keep the HAT on. Neuron 42:879–881

    PubMed  CAS  Google Scholar 

  • Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, Fan G, Sun YE (2003) DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 302:890–893

    PubMed  CAS  Google Scholar 

  • Marutha Ravindran CR, Ticku MK (2004) Changes in methylation pattern of NMDA receptor NR2B gene in cortical neurons after chronic ethanol treatment in mice. Brain Res Mol Brain Res 121:19–27

    PubMed  CAS  Google Scholar 

  • Matevossian A, Akbarian S (2008) Neuronal nuclei isolation from human postmortem brain tissue. J Vis Exp 20:pii: 914. doi: 10.3791/914

    Google Scholar 

  • Mattick JS, Makunin IV (2006) Non-coding RNA. Hum Mol Genet 15(Spec No. 1):R17–R29

    PubMed  CAS  Google Scholar 

  • McGowan PO, Sasaki A, Huang TC, Unterberger A, Suderman M, Ernst C, Meaney MJ, Turecki G, Szyf M (2008) Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS ONE 3:e2085

    PubMed  Google Scholar 

  • McGowan PO, Sasaki A, D’Alessio AC, Dymov S, Labonte B, Szyf M, Turecki G, Meaney MJ (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 12:342–348

    PubMed  CAS  Google Scholar 

  • Mellios N, Huang HS, Baker SP, Galdzicka M, Ginns E, Akbarian S (2008) Molecular determinants of dysregulated GABAergic gene expression in the prefrontal cortex of subjects with schizophrenia. Biol Psychiatry 65:1006–1014

    Google Scholar 

  • Mill J, Tang T, Kaminsky Z, Khare T, Yazdanpanah S, Bouchard L, Jia P, Assadzadeh A, Flanagan J, Schumacher A, Wang SC, Petronis A (2008) Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. Am J Hum Genet 82:696–711

    PubMed  CAS  Google Scholar 

  • Monteggia LM, Kavalali ET (2009) Rett syndrome and the impact of MeCP2 associated transcriptional mechanisms on neurotransmission. Biol Psychiatry 65:204–210

    PubMed  CAS  Google Scholar 

  • Morgan HD, Santos F, Green K, Dean W, Reik W (2005) Epigenetic reprogramming in mammals. Hum Mol Genet 14(Spec No 1):R47–R58

    PubMed  CAS  Google Scholar 

  • Nelson ED, Kavalali ET, Monteggia LM (2008) Activity-dependent suppression of miniature neurotransmission through the regulation of DNA methylation. J Neurosci 28:395–406

    PubMed  CAS  Google Scholar 

  • Numachi Y, Yoshida S, Yamashita M, Fujiyama K, Naka M, Matsuoka H, Sato M, Sora I (2004) Psychostimulant alters expression of DNA methyltransferase mRNA in the rat brain. Ann NY Acad Sci 1025:102–109

    PubMed  CAS  Google Scholar 

  • Numachi Y, Shen H, Yoshida S, Fujiyama K, Toda S, Matsuoka H, Sora I, Sato M (2007) Methamphetamine alters expression of DNA methyltransferase 1 mRNA in rat brain. Neurosci Lett 414:213–217

    PubMed  CAS  Google Scholar 

  • Ooi SK, Bestor TH (2008) The colorful history of active DNA demethylation. Cell 133:1145–1148

    PubMed  CAS  Google Scholar 

  • Pae CU, Serretti A, Mandelli L, Yu HS, Patkar AA, Lee CU, Lee SJ, Jun TY, Lee C, Paik IH, Kim JJ (2007) Effect of 5-haplotype of dysbindin gene (DTNBP1) polymorphisms for the susceptibility to bipolar I disorder. Am J Med Genet B Neuropsychiatr Genet 144:701–703

    Google Scholar 

  • Payer B, Lee JT (2008) X chromosome dosage compensation: how mammals keep the balance. Annu Rev Genet 42:733–732

    PubMed  CAS  Google Scholar 

  • Peterson CL (2002) Chromatin remodeling: nucleosomes bulging at the seams. Curr Biol 12:R245–R247

    PubMed  CAS  Google Scholar 

  • Peterson CL, Laniel MA (2004) Histones and histone modifications. Curr Biol 14:R546–R551

    PubMed  CAS  Google Scholar 

  • Polesskaya OO, Aston C, Sokolov BP (2006) Allele C-specific methylation of the 5-HT2A receptor gene: evidence for correlation with its expression and expression of DNA methylase DNMT1. J Neurosci Res 83:362–373

    PubMed  CAS  Google Scholar 

  • Rampon C, Jiang CH, Dong H, Tang YP, Lockhart DJ, Schultz PG, Tsien JZ, Hu Y (2000) Effects of environmental enrichment on gene expression in the brain. Proc Natl Acad Sci USA 97:12880–12884

    PubMed  CAS  Google Scholar 

  • Raybould R, Green EK, MacGregor S, Gordon-Smith K, Heron J, Hyde S, Caesar S, Nikolov I, Williams N, Jones L, O’Donovan MC, Owen MJ, Jones I, Kirov G, Craddock N (2005) Bipolar disorder and polymorphisms in the dysbindin gene (DTNBP1). Biol Psychiatry 57:696–701

    PubMed  CAS  Google Scholar 

  • Rosen LB, Ginty DD, Weber MJ, Greenberg ME (1994) Membrane depolarization and calcium influx stimulate MEK and MAP kinase via activation of Ras. Neuron 12:1207–1221

    PubMed  CAS  Google Scholar 

  • Salnikow K, Zhitkovich A (2008) Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic, and chromium. Chem Res Toxicol 21:28–44

    PubMed  Google Scholar 

  • Satta R, Maloku E, Costa E, Guidotti A (2007) Stimulation of brain nicotinic acetylcholine receptors (nAChRs) decreases DNA methyltransferase 1 (DNMT1) expression in cortical and hippocampal GABAergic neurons of Swiss albino mice. Soc Neurosci Abstr no. 60.7

    Google Scholar 

  • Satta R, Maloku E, Zhubi A, Pibiri F, Hajos M, Costa E, Guidotti A (2008) Nicotine decreases DNA methyltransferase 1 expression and glutamic acid decarboxylase 67 promoter methylation in GABAergic interneurons. Proc Natl Acad Sci USA 105:16356–16361

    PubMed  CAS  Google Scholar 

  • Seila AC, Calabrese JM, Levine SS, Yeo GW, Rahl PB, Flynn RA, Young RA, Sharp PA (2008) Divergent transcription from active promoters. Science 322:1849–1851

    PubMed  CAS  Google Scholar 

  • Sessa L, Breiling A, Lavorgna G, Silvestri L, Casari G, Orlando V (2007) Noncoding RNA synthesis and loss of polycomb group repression accompanies the colinear activation of the human HOXA cluster. RNA 13:223–239

    PubMed  CAS  Google Scholar 

  • Shimabukuro M, Jinno Y, Fuke C, Okazaki Y (2006) Haloperidol treatment induces tissue- and sex-specific changes in DNA methylation: a control study using rats. Behav Brain Funct 2:37

    PubMed  Google Scholar 

  • Siegmund KD, Connor CM, Campan M, Long TI, Weisenberger DJ, Biniszkiewicz D, Jaenisch R, Laird PW, Akbarian S (2007) DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons. PLoS ONE 2:e895

    PubMed  Google Scholar 

  • Smith M (2009) The year in human and medical genetics. Highlights of 2007–2008. Ann NY Acad Sci 1151:1–21

    PubMed  Google Scholar 

  • Stadler F, Kolb G, Rubusch L, Baker SP, Jones EG, Akbarian S (2005) Histone methylation at gene promoters is associated with developmental regulation and region-specific expression of ionotropic and metabotropic glutamate receptors in human brain. J Neurochem 94:324–336

    PubMed  CAS  Google Scholar 

  • Straub RE, Jiang Y, MacLean CJ, Ma Y, Webb BT, Myakishev MV, Harris-Kerr C, Wormley B, Sadek H, Kadambi B, Cesare AJ, Gibberman A, Wang X, O’Neill FA, Walsh D, Kendler KS (2002) Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia. Am J Hum Genet 71:337–348

    PubMed  CAS  Google Scholar 

  • Suzuki MM, Bird A (2008) DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 9:465–476

    PubMed  CAS  Google Scholar 

  • Swank MW, Sweatt JD (2001) Increased histone acetyltransferase and lysine acetyltransferase activity and biphasic activation of the ERK/RSK cascade in insular cortex during novel taste learning. J Neurosci 21:3383–3391

    PubMed  CAS  Google Scholar 

  • Sweatt JD (2001) The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. J Neurochem 76:1–10

    PubMed  CAS  Google Scholar 

  • Sweatt JD (2009) Experience-dependent epigenetic modifications in the central nervous system. Biol Psychiatry 65:191–197

    PubMed  Google Scholar 

  • Szyf M (2009) Epigenetics, DNA methylation, and chromatin modifying drugs. Annu Rev Pharmacol Toxicol 49:243–263

    PubMed  CAS  Google Scholar 

  • Tamura Y, Kunugi H, Ohashi J, Hohjoh H (2007) Epigenetic aberration of the human REELIN gene in psychiatric disorders. Mol Psychiatry 12:593–600

    CAS  Google Scholar 

  • The International Schizophrenia Consortium (2008) Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455:237–241

    Google Scholar 

  • Tochigi M, Iwamoto K, Bundo M, Komori A, Sasaki T, Kato N, Kato T (2008) Methylation status of the reelin promoter region in the brain of schizophrenic patients. Biol Psychiatry 63:530–533

    PubMed  CAS  Google Scholar 

  • Tsankova NM, Kumar A, Nestler EJ (2004) Histone modifications at gene promoter regions in rat hippocampus after acute and chronic electroconvulsive seizures. J Neurosci 24:5603–5610

    PubMed  CAS  Google Scholar 

  • Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ (2006) Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci 9:519–525

    PubMed  CAS  Google Scholar 

  • Tsankova N, Renthal W, Kumar A, Nestler EJ (2007) Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci 8:355–367

    PubMed  CAS  Google Scholar 

  • Veldic M, Caruncho HJ, Liu WS, Davis J, Satta R, Grayson DR, Guidotti A, Costa E (2004) DNA-methyltransferase 1 mRNA is selectively overexpressed in telencephalic GABAergic interneurons of schizophrenia brains. Proc Natl Acad Sci USA 101:348–353

    PubMed  CAS  Google Scholar 

  • Veldic M, Guidotti A, Maloku E, Davis JM, Costa E (2005) In psychosis, cortical interneurons overexpress DNA-methyltransferase 1. Proc Natl Acad Sci USA 102:2152–2157

    PubMed  CAS  Google Scholar 

  • Waggoner D (2007) Mechanisms of disease: epigenesis. Semin Pediatr Neurol 14:7–14

    PubMed  Google Scholar 

  • Wang Y, Fischle W, Cheung W, Jacobs S, Khorasanizadeh S, Allis CD (2004) Beyond the double helix: writing and reading the histone code. Novartis Found Symp 259:3–17, discussion 17–21, 163–169

    PubMed  CAS  Google Scholar 

  • Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7:847–854

    PubMed  CAS  Google Scholar 

  • Wolffe AP (1992) New insights into chromatin function in transcriptional control. FASEB J 6:3354–3361

    PubMed  CAS  Google Scholar 

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Acknowledgments

Research conducted by the author is supported by grants from the National Institutes of Health and the Staglin Family Music Festival Schizophrenia Research Award/NARSAD. The author reports no conflicts of interest.

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  1. Department of Psychiatry, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, MA, 01604, USA

    Schahram Akbarian

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  1. Schahram Akbarian
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Correspondence to Schahram Akbarian .

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  1. , Dept. of Psychiatry - MC 0804, University of San Diego, Gilman Drive 9500, La Jolla, 92093, USA

    Neal R. Swerdlow

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Akbarian, S. (2010). Epigenetics of Schizophrenia. In: Swerdlow, N. (eds) Behavioral Neurobiology of Schizophrenia and Its Treatment. Current Topics in Behavioral Neurosciences, vol 4. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2010_38

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