Skip to main content
SpringerLink
Log in

Posttranslational Histone Modifications and the Neurobiology of Psychosis

  • Chapter
  • First Online:
Brain, Behavior and Epigenetics

Part of the book series: Epigenetics and Human Health ((EHH))

  • 1650 Accesses

Abstract

Schizophrenia and related major psychiatric disease is typically defined by the conspicuous absence of a defining neuropathology and a lack of straightforward identifiable genetic factors in the majority of affected individuals. On the other hand, there is increasing evidence that a distinct set of RNAs, many of which encode proteins of critical importance for myelin regulation and oligodendrocyte function, or GABAergic inhibitory and glutamatergic excitatory neurotransmission are expressed at altered levels in diseased brain. This chapter explores the mechanisms by which epigenetic regulators of gene expression, including covalent histone modifications, could contribute to dysregulation of gene expression in schizophrenia. There is also discussion on the methodological and scientific limitations of histone-focused approaches, as it pertains to the human (postmortem) brain, as well as brief remarks on the topic of epigenetic heritability of chromatin structures potentially altered in schizophrenia. The authors predict that the study of histone modifications, both at defined candidate gene loci and genome-wide, will become an important tool in the investigation of gene expression abnormalities and potential epigenetic dysregulation in the brains of subjects on the psychosis spectrum.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ATP:

Adenosine triphosphate

DRD2:

Dopamine receptor D2

ERBB4:

Receptor tyrosine kinase erb4

GABA:

Gamma-aminobutryic acid

GABRA2:

GABA-A receptor, alpha 2 subunit

GAD1:

Glutamic acid decarboxylase 1

GAD67:

67 kDa glutamic acid decarboxylase (=GAD67)

GRIN1:

Glutamate receptor, ionotropic 1

GRM3:

Glutamate receptor, metabotropic 3

H3K4me1:

Histone H3-monomethyl-lysine 4

H3K4me2:

Histone H3-dimethyl-lysine 4

H3K4me3:

Histone H3-trimethyl-lysine 4

HDAC:

Histone deacetylase

HDACi:

Histone deacetylase inhibitor

Hz:

Hertz

K:

Lysine

KDM:

Histone lysine demethylase

KTM:

Histone lysine methyltransferase

Mll1:

Mixed lineage leukemia 1 (histone methyltransferase)

mRNA:

Messenger ribonucleic acid

NMDA:

N-methyl-d-aspartate

SNP:

Single nucleotide polymorphism

SUMO:

Small ubiqutin related modifier

VPA:

Valproic acid

References

  • 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 

  • Abi-Dargham A, van de Giessen E, Slifstein M, Kegeles LS, Laruelle M (2009) Baseline and amphetamine-stimulated dopamine activity are related in drug-naive schizophrenic subjects. Biol Psychiatry 65:1091–1093

    PubMed  CAS  Google Scholar 

  • Addington AM, Gornick M, Duckworth J, Sporn A, Gogtay N, Bobb A, Greenstein D, Lenane M, Gochman P, Baker N et al (2005) GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss. Mol Psychiatry 10:581–588

    PubMed  CAS  Google Scholar 

  • Akbarian S, Huang HS (2006) Molecular and cellular mechanisms of altered GAD1/GAD67 expression in schizophrenia and related disorders. Brain Res Rev 52:293–304

    PubMed  CAS  Google Scholar 

  • Akbarian S, Kim JJ, Potkin SG, Hetrick WP, Bunney WE Jr, Jones EG (1996) Maldistribution of interstitial neurons in prefrontal white matter of the brains of schizophrenic patients. Arch Gen Psychiatry 53:425–436

    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 

  • Aston C, Jiang L, Sokolov BP (2004) Microarray analysis of postmortem temporal cortex from patients with schizophrenia. J Neurosci Res 77:858–866

    PubMed  CAS  Google Scholar 

  • Barch DM (2005) The cognitive neuroscience of schizophrenia. Annu Rev Clin Psychol 1:321–353

    PubMed  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 

  • Belforte JE, Zsiros V, Sklar ER, Jiang Z, Yu G, Li Y, Quinlan EM, Nakazawa K (2010) Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes. Nat Neurosci 13:76–83

    PubMed  CAS  Google Scholar 

  • Benes FM (2010) Amygdalocortical circuitry in schizophrenia: from circuits to molecules. Neuropsychopharmacology 35:239–257

    PubMed  Google Scholar 

  • Beneyto M, Kristiansen LV, Oni-Orisan A, McCullumsmith RE, Meador-Woodruff JH (2007) Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders. Neuropsychopharmacology 32:1888–1902

    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 

  • Bernstein BE, Kamal M, Lindblad-Toh K, Bekiranov S, Bailey DK, Huebert DJ, McMahon S, Karlsson EK, Kulbokas EJ 3rd, Gingeras TR et al (2005) Genomic maps and comparative analysis of histone modifications in human and mouse. Cell 120:169–181

    PubMed  CAS  Google Scholar 

  • Bertran-Gonzalez J, Bosch C, Maroteaux M, Matamales M, Herve D, Valjent E, Girault JA (2008) Opposing patterns of signaling activation in dopamine D1 and D2 receptor-expressing striatal neurons in response to cocaine and haloperidol. J Neurosci 28:5671–5685

    PubMed  CAS  Google Scholar 

  • Bertran-Gonzalez J, Hakansson K, Borgkvist A, Irinopoulou T, Brami-Cherrier K, Usiello A, Greengard P, Herve D, Girault JA, Valjent E et al (2009) Histone H3 phosphorylation is under the opposite tonic control of dopamine D2 and adenosine A2A receptors in striatopallidal neurons. Neuropsychopharmacology 34:1710–1720

    PubMed  CAS  Google Scholar 

  • Bezek S, Ujhazy E, Dubovicky M, Mach M (2008) Nongenomic memory of foetal history in chronic diseases development. Neuro Endocrinol Lett 29:620–626

    PubMed  Google Scholar 

  • Biron VL, McManus KJ, Hu N, Hendzel MJ, Underhill DA (2004) Distinct dynamics and distribution of histone methyl-lysine derivatives in mouse development. Dev Biol 276:337–351

    PubMed  CAS  Google Scholar 

  • Buckley NJ (2007) Analysis of transcription, chromatin dynamics and epigenetic changes in neural genes. Prog Neurobiol 83:195–210

    PubMed  CAS  Google Scholar 

  • Canoso RT, de Oliveira RM (1986) Characterization and antigenic specificity of chlorpromazine-induced antinuclear antibodies. J Lab Clin Med 108:213–216

    PubMed  CAS  Google Scholar 

  • Charych EI, Liu F, Moss SJ, Brandon NJ (2009) GABA(A) receptors and their associated proteins: implications in the etiology and treatment of schizophrenia and related disorders. Neuropharmacology 57:481–495

    PubMed  CAS  Google Scholar 

  • Colantuoni C, Hyde TM, Mitkus S, Joseph A, Sartorius L, Aguirre C, Creswell J, Johnson E, Deep-Soboslay A, Herman MM et al (2008) Age-related changes in the expression of schizophrenia susceptibility genes in the human prefrontal cortex. Brain Struct Funct 213:255–271

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Connor CM, Guo Y, Akbarian S (2009) Cingulate white matter neurons in schizophrenia and bipolar disorder. Biol Psychiatry 66:486–493

    PubMed  Google Scholar 

  • Doherty SP, Grabowski J, Hoffman C, Ng SP, Zelikoff JT (2009) Early life insult from cigarette smoke may be predictive of chronic diseases later in life. Biomarkers 14(Suppl 1):97–101

    PubMed  CAS  Google Scholar 

  • Dong E, Guidotti A, Grayson DR, Costa E (2007) Histone hyperacetylation induces demethylation of reelin and 67-kDa glutamic acid decarboxylase promoters. Proc Natl Acad Sci USA 104:4676–4681

    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 

  • Duman RS, Newton SS (2007) Epigenetic marking and neuronal plasticity. Biol Psychiatry 62:1–3

    PubMed  Google Scholar 

  • Duncan CE, Webster MJ, Rothmond DA, Bahn S, Elashoff M, Shannon Weickert C (2010) Prefrontal GABA(A) receptor alpha-subunit expression in normal postnatal human development and schizophrenia. J Psychiatr Res 44:673–681

    PubMed  Google Scholar 

  • Eastwood SL, Harrison PJ (2005) Interstitial white matter neuron density in the dorsolateral prefrontal cortex and parahippocampal gyrus in schizophrenia. Schizophr Res 79:181–188

    PubMed  CAS  Google Scholar 

  • Eissenberg JC, Shilatifard A (2006) Leaving a mark: the many footprints of the elongating RNA polymerase II. Curr Opin Genet Dev 16:184–190

    PubMed  CAS  Google Scholar 

  • Ernst C, Chen ES, Turecki G (2009) Histone methylation and decreased expression of TrkB.T1 in orbital frontal cortex of suicide completers. Mol Psychiatry 14:830–832

    PubMed  CAS  Google Scholar 

  • Falkai P, Schneider-Axmann T, Honer WG (2000) Entorhinal cortex pre-alpha cell clusters in schizophrenia: quantitative evidence of a developmental abnormality. Biol Psychiatry 47:937–943

    PubMed  CAS  Google Scholar 

  • Feinberg AP (2004) The epigenetics of cancer etiology. Semin Cancer Biol 14:427–432

    PubMed  CAS  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 

  • Feng J, Fouse S, Fan G (2007) Epigenetic regulation of neural gene expression and neuronal function. Pediatr Res 61:58R–63R

    PubMed  CAS  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 

  • Fuster JM (2002) Frontal lobe and cognitive development. J Neurocytol 31:373–385

    PubMed  Google Scholar 

  • Gardner DS, Bell RC, Symonds ME (2007) Fetal mechanisms that lead to later hypertension. Curr Drug Targets 8:894–905

    PubMed  CAS  Google Scholar 

  • Gavin DP, Sharma RP (2009) Histone modifications, DNA methylation, and Schizophrenia. Neurosci Biobehav Rev 34:882–888

    PubMed  Google Scholar 

  • Goff DC, Evins AE (1998) Negative symptoms in schizophrenia: neurobiological models and treatment response. Harv Rev Psychiatry 6:59–77

    PubMed  CAS  Google Scholar 

  • Graff J, Mansuy IM (2008) Epigenetic codes in cognition and behaviour. Behav Brain Res 192:70–87

    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 

  • Guenther MG, Levine SS, Boyer LA, Jaenisch R, Young RA (2007) A chromatin landmark and transcription initiation at most promoters in human cells. Cell 130:77–88

    PubMed  CAS  Google Scholar 

  • Guidotti A, Auta J, Davis JM, Dong E, Grayson DR, Veldic M, Zhang X, Costa E (2005) GABAergic dysfunction in schizophrenia: new treatment strategies on the horizon. Psychopharmacol (Berl) 180:191–205

    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 

  • Hager GL, McNally JG, Misteli T (2009) Transcription dynamics. Mol Cell 35:741–753

    PubMed  CAS  Google Scholar 

  • Hakak Y, Walker JR, Li C, Wong WH, Davis KL, Buxbaum JD, Haroutunian V, Fienberg AA (2001) Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc Natl Acad Sci USA 98:4746–4751

    PubMed  CAS  Google Scholar 

  • Hammoud SS, Nix DA, Zhang H, Purwar J, Carrell DT, Cairns BR (2009) Distinctive chromatin in human sperm packages genes for embryo development. Nature 460:473–478

    PubMed  CAS  Google Scholar 

  • Harris LW, Lockstone HE, Khaitovich P, Weickert CS, Webster MJ, Bahn S (2009) Gene expression in the prefrontal cortex during adolescence: implications for the onset of schizophrenia. BMC Med Genomics 2:28

    PubMed  Google Scholar 

  • Harrison PJ (1999) The neuropathology of schizophrenia. A critical review of the data and their interpretation. Brain 122(Pt 4):593–624

    PubMed  Google Scholar 

  • Harrison PJ, Weinberger DR (2005) Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 10:40–68

    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 

  • Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD, Barrera LO, Van Calcar S, Qu C, Ching KA et al (2007) Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet 39:311–318

    PubMed  CAS  Google Scholar 

  • Hemby SE, Ginsberg SD, Brunk B, Arnold SE, Trojanowski JQ, Eberwine JH (2002) Gene expression profile for schizophrenia: discrete neuron transcription patterns in the entorhinal cortex. Arch Gen Psychiatry 59:631–640

    PubMed  CAS  Google Scholar 

  • Hof PR, Haroutunian V, Friedrich VL Jr, Byne W, Buitron C, Perl DP, Davis KL (2003) Loss and altered spatial distribution of oligodendrocytes in the superior frontal gyrus in schizophrenia. Biol Psychiatry 53:1075–1085

    PubMed  CAS  Google Scholar 

  • Hoistad M, Segal D, Takahashi N, Sakurai T, Buxbaum JD, Hof PR (2009) Linking white and grey matter in schizophrenia: oligodendrocyte and neuron pathology in the prefrontal cortex. Front Neuroanat 3:9

    PubMed  Google Scholar 

  • Homayoun H, Moghaddam B (2007) NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J Neurosci 27:11496–11500

    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 Meth 156:284–292

    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 

  • Ikeda K, Iritani S, Ueno H, Niizato K (2004) Distribution of neuropeptide Y interneurons in the dorsal prefrontal cortex of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 28:379–383

    PubMed  CAS  Google Scholar 

  • Impagnatiello F, Guidotti AR, Pesold C, Dwivedi Y, Caruncho H, Pisu MG, Uzunov DP, Smalheiser NR, Davis JM, Pandey GN et al (1998) A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Proc Natl Acad Sci USA 95:15718–15723

    PubMed  CAS  Google Scholar 

  • Iritani S (2007) Neuropathology of schizophrenia: a mini review. Neuropathology 27:604–608

    PubMed  Google Scholar 

  • Jakob H, Beckmann H (1986) Prenatal developmental disturbances in the limbic allocortex in schizophrenics. J Neural Transm 65:303–326

    PubMed  CAS  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 

  • Katsel P, Davis KL, Haroutunian V (2005) Variations in myelin and oligodendrocyte-related gene expression across multiple brain regions in schizophrenia: a gene ontology study. Schizophr Res 79:157–173

    PubMed  Google Scholar 

  • Khaitovich P, Lockstone HE, Wayland MT, Tsang TM, Jayatilaka SD, Guo AJ, Zhou J, Somel M, Harris LW, Holmes E et al (2008) Metabolic changes in schizophrenia and human brain evolution. Genome Biol 9:R124

    PubMed  Google Scholar 

  • Kirkpatrick B, Conley RC, Kakoyannis A, Reep RL, Roberts RC (1999) Interstitial cells of the white matter in the inferior parietal cortex in schizophrenia: an unbiased cell-counting study. Synapse 34:95–102

    PubMed  CAS  Google Scholar 

  • Kirov G (2010) The role of copy number variation in schizophrenia. Expert Rev Neurother 10:25–32

    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 

  • 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 

  • Kumar R, Holian O, Cook B, Roshani P (1997) Inhibition of rat brain protein kinase C by lipid soluble psychotropics. Neurochem Res 22:1–10

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Kunugi H, Nanko S, Murray RM (2001) Obstetric complications and schizophrenia: prenatal underdevelopment and subsequent neurodevelopmental impairment. Br J Psychiatry Suppl 40:s25–s29

    PubMed  CAS  Google Scholar 

  • Leng Y, Liang MH, Ren M, Marinova Z, Leeds P, Chuang DM (2008) Synergistic neuroprotective effects of lithium and valproic acid or other histone deacetylase inhibitors in neurons: roles of glycogen synthase kinase-3 inhibition. J Neurosci 28:2576–2588

    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 

  • Lewis DA, Levitt P (2002) Schizophrenia as a disorder of neurodevelopment. Annu Rev Neurosci 25:409–432

    PubMed  CAS  Google Scholar 

  • Lewis DA, Mirnics K (2006) Transcriptome alterations in schizophrenia: disturbing the functional architecture of the dorsolateral prefrontal cortex. Prog Brain Res 158:141–152

    PubMed  CAS  Google Scholar 

  • Lewis DA, Cho RY, Carter CS, Eklund K, Forster S, Kelly MA, Montrose D (2008) Subunit-selective modulation of GABA type A receptor neurotransmission and cognition in schizophrenia. Am J Psychiatry 165:1585–1593

    PubMed  Google Scholar 

  • Li E (2002) Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet 3:662–673

    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 

  • Li H, Ilin S, Wang W, Duncan EM, Wysocka J, Allis CD, Patel DJ (2006) Molecular basis for site-specific read-out of histone H3K4me3 by the BPTF PHD finger of NURF. Nature 442:91–95

    PubMed  CAS  Google Scholar 

  • Lim KO, Hedehus M, Moseley M, de Crespigny A, Sullivan EV, Pfefferbaum A (1999) Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging. Arch Gen Psychiatry 56:367–374

    PubMed  CAS  Google Scholar 

  • Lipska BK, Mitkus SN, Mathew SV, Fatula R, Hyde TM, Weinberger DR, Kleinman JE (2006) Functional genomics in postmortem human brain: abnormalities in a DISC1 molecular pathway in schizophrenia. Dialogues Clin Neurosci 8:353–357

    PubMed  Google Scholar 

  • Lisman JE, Coyle JT, Green RW, Javitt DC, Benes FM, Heckers S, Grace AA (2008) Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci 31:234–242

    PubMed  CAS  Google Scholar 

  • Loncar-Stevanovic H, Vujovic Z, Drazic A, Lazic D, Jakulic S, Jovanovic T (1998) The influence of selenium and neuroleptics on the rat brain nuclear regulatory mechanism in carcinogenesis. J Environ Pathol Toxicol Oncol 17:331–337

    PubMed  CAS  Google Scholar 

  • Maekawa M, Watanabe Y (2007) Epigenetics: relations to disease and laboratory findings. Curr Med Chem 14:2642–2653

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Martins-de-Souza D, Gattaz WF, Schmitt A, Rewerts C, Marangoni S, Novello JC, Maccarrone G, Turck CW, Dias-Neto E (2009) Alterations in oligodendrocyte proteins, calcium homeostasis and new potential markers in schizophrenia anterior temporal lobe are revealed by shotgun proteome analysis. J Neural Transm 116:275–289

    PubMed  CAS  Google Scholar 

  • Matevossian A, Akbarian S (2008) Neuronal nuclei isolation from human postmortem brain tissue. J Vis Exp (20)

    Google Scholar 

  • Meador-Woodruff JH, Healy DJ (2000) Glutamate receptor expression in schizophrenic brain. Brain Res Brain Res Rev 31:288–294

    PubMed  CAS  Google Scholar 

  • Meltzer HY (2004) What's atypical about atypical antipsychotic drugs? Curr Opin Pharmacol 4:53–57

    PubMed  CAS  Google Scholar 

  • Middleton FA, Mirnics K, Pierri JN, Lewis DA, Levitt P (2002) Gene expression profiling reveals alterations of specific metabolic pathways in schizophrenia. J Neurosci 22:2718–2729

    PubMed  CAS  Google Scholar 

  • Narayan S, Kass KE, Thomas EA (2007) Chronic haloperidol treatment results in a decrease in the expression of myelin/oligodendrocyte-related genes in the mouse brain. J Neurosci Res 85:757–765

    PubMed  CAS  Google Scholar 

  • Northcott PA, Nakahara Y, Wu X, Feuk L, Ellison DW, Croul S, Mack S, Kongkham PN, Peacock J, Dubuc A et al (2009) Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma. Nat Genet 41:465–472

    PubMed  CAS  Google Scholar 

  • Novikova SI, He F, Bai J, Cutrufello NJ, Lidow MS, Undieh AS (2008) Maternal cocaine administration in mice alters DNA methylation and gene expression in hippocampal neurons of neonatal and prepubertal offspring. PLoS ONE 3:e1919

    PubMed  Google Scholar 

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

    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 

  • Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA, Klein PS (2001) Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem 276:36734–36741

    PubMed  CAS  Google Scholar 

  • Pongrac JL, Middleton FA, Peng L, Lewis DA, Levitt P, Mirnics K (2004) Heat shock protein 12A shows reduced expression in the prefrontal cortex of subjects with schizophrenia. Biol Psychiatry 56:943–950

    PubMed  CAS  Google Scholar 

  • Potkin SG, Ford JM (2009) Widespread cortical dysfunction in schizophrenia: the FBIRN imaging consortium. Schizophr Bull 35:15–18

    PubMed  Google Scholar 

  • Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, Sullivan PF, Sklar P (2009) Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460:748–752

    PubMed  CAS  Google Scholar 

  • Regenold WT, Phatak P, Marano CM, Gearhart L, Viens CH, Hisley KC (2007) Myelin staining of deep white matter in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and unipolar major depression. Psychiatry Res 151:179–188

    PubMed  CAS  Google Scholar 

  • Renthal W, Nestler EJ (2008) Epigenetic mechanisms in drug addiction. Trends Mol Med 14:341–350

    PubMed  CAS  Google Scholar 

  • Rioux L, Nissanov J, Lauber K, Bilker WB, Arnold SE (2003) Distribution of microtubule-associated protein MAP2-immunoreactive interstitial neurons in the parahippocampal white matter in subjects with schizophrenia. Am J Psychiatry 160:149–155

    PubMed  Google Scholar 

  • Roberts CT (2010) Review: complicated interactions between genes and the environment in placentation, pregnancy outcome and long term health. Placenta 31:107

    Google Scholar 

  • Schmitt A, Steyskal C, Bernstein HG, Schneider-Axmann T, Parlapani E, Schaeffer EL, Gattaz WF, Bogerts B, Schmitz C, Falkai P (2009) Stereologic investigation of the posterior part of the hippocampus in schizophrenia. Acta Neuropathol 117:395–407

    PubMed  Google Scholar 

  • Schroeder FA, Penta KL, Matevossian A, Jones SR, Konradi C, Tapper AR, Akbarian S (2008) Drug-induced activation of dopamine D(1) receptor signaling and inhibition of class I/II histone deacetylase induce chromatin remodeling in reward circuitry and modulate cocaine-related behaviors. Neuropsychopharmacology 33:2981–2992

    PubMed  CAS  Google Scholar 

  • Segalowitz SJ, Davies PL (2004) Charting the maturation of the frontal lobe: an electrophysiological strategy. Brain Cogn 55:116–133

    PubMed  CAS  Google Scholar 

  • Sharma RP, Rosen C, Kartan S, Guidotti A, Costa E, Grayson DR, Chase K (2006) Valproic acid and chromatin remodeling in schizophrenia and bipolar disorder: preliminary results from a clinical population. Schizophr Res 88:227–231

    PubMed  Google Scholar 

  • Shi J, Levinson DF, Duan J, Sanders AR, Zheng Y, Pe'er I, Dudbridge F, Holmans PA, Whittemore AS, Mowry BJ et al (2009) Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature 460:753–757

    PubMed  CAS  Google Scholar 

  • Shilatifard A (2008) Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation. Curr Opin Cell Biol 20:341–348

    PubMed  CAS  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 

  • Simmons RA (2009) Developmental origins of adult disease. Pediatr Clin North Am 56:449–466

    PubMed  Google Scholar 

  • Simonini MV, Camargo LM, Dong E, Maloku E, Veldic M, Costa E, Guidotti A (2006) The benzamide MS-275 is a potent, long-lasting brain region-selective inhibitor of histone deacetylases. Proc Natl Acad Sci USA 103:1587–1592

    PubMed  CAS  Google Scholar 

  • Sohal VS, Zhang F, Yizhar O, Deisseroth K (2009) Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 459:698–702

    PubMed  CAS  Google Scholar 

  • Somel M, Franz H, Yan Z, Lorenc A, Guo S, Giger T, Kelso J, Nickel B, Dannemann M, Bahn S et al (2009) Transcriptional neoteny in the human brain. Proc Natl Acad Sci USA 106:5743–5748

    PubMed  CAS  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 

  • Stefanis CN, Issidorides MR (1976) Histochemical changes in the blood cells of schizophrenic patients under pimozide treatment. Biol Psychiatry 11:53–68

    PubMed  CAS  Google Scholar 

  • Straub RE, Lipska BK, Egan MF, Goldberg TE, Kleinman JE, Weinberger DR (2007) Allelic variation in GAD1 (GAD67) is associated with schizophrenia and influences cortical function and gene expression. Mol Psychiatry 12:854–869

    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 

  • Tandon R, Keshavan MS, Nasrallah HA (2008) Schizophrenia, “just the facts” what we know in 2008. 2. Epidemiology and etiology. Schizophr Res 102:1–18

    PubMed  Google Scholar 

  • Tkachev D, Mimmack ML, Ryan MM, Wayland M, Freeman T, Jones PB, Starkey M, Webster MJ, Yolken RH, Bahn S (2003) Oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet 362:798–805

    PubMed  CAS  Google Scholar 

  • Torrey EF, Barci BM, Webster MJ, Bartko JJ, Meador-Woodruff JH, Knable MB (2005) Neurochemical markers for schizophrenia, bipolar disorder, and major depression in postmortem brains. Biol Psychiatry 57:252–260

    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 

  • Uhlhaas PJ, Singer W (2010) Abnormal neural oscillations and synchrony in schizophrenia. Nat Rev Neurosci 11:100–113

    PubMed  CAS  Google Scholar 

  • Uranova NA, Vostrikov VM, Orlovskaya DD, Rachmanova VI (2004) Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium. Schizophr Res 67:269–275

    PubMed  Google Scholar 

  • Vawter MP, Tomita H, Meng F, Bolstad B, Li J, Evans S, Choudary P, Atz M, Shao L, Neal C et al (2006) Mitochondrial-related gene expression changes are sensitive to agonal-pH state: implications for brain disorders. Mol Psychiatry 11(615):663–679

    CAS  Google Scholar 

  • Volk DW, Austin MC, Pierri JN, Sampson AR, Lewis DA (2000) Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyric acid neurons in subjects with schizophrenia. Arch Gen Psychiatry 57:237–245

    PubMed  CAS  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 

  • White T, Magnotta VA, Bockholt HJ, Williams S, Wallace S, Ehrlich S, Mueller BA, Ho BC, Jung RE, Clark VP et al (2009) Global white matter abnormalities in schizophrenia: a multisite diffusion tensor imaging study. Schizophr Bull 37:222–232

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Woo TU, Kim AM, Viscidi E (2008) Disease-specific alterations in glutamatergic neurotransmission on inhibitory interneurons in the prefrontal cortex in schizophrenia. Brain Res 1218:267–277

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Work in the authors’ laboratory is supported by grants from the National Institute of Health, the Deutsche Forschungsgemeinschaft, and the International Mental Health Research Organization (IMHRO).

Author information

Authors and Affiliations

  1. Department of Psychiatry, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, 303 Belmont Street, Worcester, MA, 01604, USA

    Schahram Akbarian, Iris Cheung, Caroline Connor, Mira Jakovcevski & Yan Jiang

Authors
  1. Schahram Akbarian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Iris Cheung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Caroline Connor
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mira Jakovcevski
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yan Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Schahram Akbarian .

Editor information

Editors and Affiliations

  1. , The Krembil Family Epigenetics Laborator, Centre for Addiction and Mental Health, College Street 250, Toronto, M5T 1R8, Ontario, Canada

    Arturas Petronis

  2. , Institute of Psychiatry, King's College London, De Crispigny Park, London, SE5 8AF, United Kingdom

    Jonathan Mill

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Akbarian, S., Cheung, I., Connor, C., Jakovcevski, M., Jiang, Y. (2011). Posttranslational Histone Modifications and the Neurobiology of Psychosis. In: Petronis, A., Mill, J. (eds) Brain, Behavior and Epigenetics. Epigenetics and Human Health. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-17426-1_1

Download citation

Publish with us

Policies and ethics

Search

Navigation