Epigenetics of bipolar disorder

Author/s
Peter Pregelj
Citation
Issue 3 Summer 2013
CEPiP.2013;1:116-122
Abstract

Bipolar disorder is a common, chronic, and recurring mental disorder with a poorly understood and complex genetic basis. Epigenetic mechanisms refer to the regulation of DNA transcription without alteration of the nucleotide sequence. Epigenetic mechanisms are: DNA methylation, histone modifications and non-coding micro RNAs. Epigenetic information is not stored in the DNA nucleotide sequence; nevertheless it can be transmitted through generations. Recent studies have indicated that epigenetic mechanisms are involved in the pathophysiology of bipolar disorder and also in the mechanisms of action of current medications used for the treatment of bipolar disorder.

Keywords: bipolar disorder, epigenetics, DNA methylation, histone modulation, micro RNAs, mood stabilizers

Cite as: Cutting Edge Psychiatry in Practice 2013, 3(1):116-122; https://doi.org/10.65031/qugf9745

References

  1. Peedicayil J. Epigenetic basis of individual variability to major psychosis. Curr Pharmacogenom Person Med (2010) 8:232-239. https://doi.org/10.2174/187569210792246290
  2. Cyranoski D. Neuropsychiatric diseases: pet project. Nature (2010)466:1036-1038.          
  3. de León-Guerrero SD, Pedraza-Alva G, Pérez-Martínez L. In sickness and in health: the role of methyl- CpG binding protein 2 in the central nervous system. Eur J Neurosci. 2011 May;33 (9):1563-74. https://doi.org/10.1111/j.1460-9568.2011.07658.x
  4. Riccio A. Dynamic epigenetic regulation in neurons: enzymes, stimuli and signaling pathways. Nat Neurosci (2010)13:1330-1337. https://doi.org/10.1038/nn.2671
  5. Vaquero A, Loyola A, Reinberg D. The constantly changing face of chromatin. Sci Aging Knowledge Environ. 2003. https://doi.org/10.1126/sageke.2003.14.re4
  6. Clapier CR, Cairns BR. The biology of chromatin remodeling complexes. Annu. Rev. Biochem. 2009;78:273-304. https://doi.org/10.1146/annurev.biochem.77.062706.153223
  7. Berger SL. The complex language of chromatin regulation during transcription. Nature. 2007;447 (7143):407-12. https://doi.org/10.1038/nature05915
  8. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128:693-705.           
  9. Kamakaka RT, Biggins S. Histone variants: deviants? Genes Dev. 2005;19:295-310. https://doi.org/10.1101/gad.1272805
  10. Li E. Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev. 2002;3:662-73.             
  11. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16:6-21.       
  12. Stein R, Gruenbaum Y, Pollack Y, Razin A, Cedar H. Clonal inheritance of the pattern of DNA methylation in mouse cells. Proc Natl Acad Sci USA. 1982;79:61-5. https://doi.org/10.1073/pnas.79.1.61
  13. Yoder JA, Soman NS, Verdine GL, Bestor TH. DNA (cytosine-5)-methyltransferases in mouse cells and tissues. Studies with a mechanism-based probe. J Mol Biol. 1997;270: 385-95. https://doi.org/10.1006/jmbi.1997.1125
  14. Grayson DR, Guidotti A. The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders. Neuropsychopharmacology. 2012 Sep 5. doi: 10.1038/npp.2012.125. https://doi.org/10.1038/npp.2012.125
  15. Razin A, Szyf M.DNA methylation patterns. Formation and function. Biochim Biophys Acta. 1984;782 (4):331-42.                
  16. Comb M, Goodman HM. CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2.Nucleic Acids Res. 1990;18 (13):3975-82. https://doi.org/10.1093/nar/18.13.3975
  17. Kusenda B; Mraz M; Mayer J. Pospisilova, S. MicroRNA biogenesis, functionality and cancer relevance. Biomedical papers. 2006;150 (2): 205-15. https://doi.org/10.5507/bp.2006.029
  18. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136 (2):215-33. https://doi.org/10.1016/j.cell.2009.01.002
  19. Bentwich I, Avniel A, Karov Y, et al. Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet. 2005;37 (7):766-70. https://doi.org/10.1038/ng1590
  20. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120 (1):15-20. https://doi.org/10.1016/j.cell.2004.12.035
  21. Pratt A; MacRae I. The RNA-induced silencing complex: a versatile gene-silencing machine. J Biol Chem. 2009;284 (27):17897-901. https://doi.org/10.1074/jbc.r900012200
  22. Murgatroyd C, Spengler D. Epigenetic programming of the HPA axis: early life decides. Stress. 2011;14 (6):581-9. https://doi.org/10.3109/10253890.2011.602146
  23. Mill J, Tang T, Kaminsky Z, et al. Epigenomic profiling reveals DNAmethylation changes associated with major psychosis. Am J Hum Genet. 2008;82:696-711.
  24. Peedicayil J. Epigenetic management of major psychosis. Clin Epigenet. 2011;2:249-56.   
  25. Veldic M, Guidotti A,Maloku E, Davis JM, Costa E In psychosis, cortical interneurons overexpress DNA-methyltransferase 1. Proc Natl Acad Sci USA. 2005;102:2152-7. https://doi.org/10.1073/pnas.0409665102
  26. Abdolmaleky HM, Cheng K-H, Faraone SV, et al. Hypomethylation of MB-COMT promoter is major risk factor for schizophrenia and bipolar disorder. Hum Mol Genet. 2006;15:3132-45. https://doi.org/10.1093/hmg/ddl253
  27. Roth TL, Sweatt JD. Epigenetic marking of the BDNF gene by early-life adverse experiences. Horm Behav. 2011;59 (3):315-20.              
  28. D’Addario C, Dell’Osso B, Palazzo MC, et al. Selective DNA methylation of BDNF promoter in bipolar disorder: differences among patients with BDI and BDII. Neuropsychopharmacol. 2012;37 (7): 1647-55. https://doi.org/10.1038/npp.2012.10
  29. Rao JS, Keleshian VL, Klein S, Rapoport SI. Epigenetic modifications in frontal cortex from Alzheimer’s disease and bipolar disorder patients. Transl Psychiatry. 2012;2:e132. https://doi.org/10.1038/tp.2012.55
  30. Dong E, Chen Y, Gavin DP, Grayson DR, Guidotti A. Valproate induces DNA demethylation in nuclear extracts from adult mouse brain. Epigenetics. 2010; 5:730-5. https://doi.org/10.4161/epi.5.8.13053
  31. Guidotti A, Auta J, Chen Y, et al. Epigenetic GABAergic targets in schizophrenia and bipolar disorder. Neuropharmacology. 20011;60:1007-16. https://doi.org/10.1016/j.neuropharm.2010.10.021
  32. Zhou R, Yuan P, Wang Y, et al. Evidence for selective microRNAs and their effectors as common long-term targets for the actions of mood stabilizers. Neuropsychopharmacology. 2009;34: 1395-405. https://doi.org/10.1038/npp.2008.131
  33. Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci. 2006;9:519-25. https://doi.org/10.1038/nn1659
  34. Cassel S, Carouge D, Gensburger C, et al. Fluoxetine and cocaine induce the epigenetic factors MeCP2 and MBD1 in adult rat brain. Mol Pharmacol. 2006;70:487-92. https://doi.org/10.1124/mol.106.022301
  35. Dong E, Nelson M, Grayson DR, Costa E, Guidotti A. Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation. Proc Natl Acad Sci U S A. 2008;105 (36):13614-9. https://doi.org/10.1073/pnas.0805493105
  36. Costa E, Chen Y, Dong E, et al. GABAergic promoter hypermethylation as a model to study the neurochemistry of schizophrenia vulnerability. Expert Rev Neurother. 2009;9 (1):87-98. https://doi.org/10.1586/14737175.9.1.87
  37. Best JD, Carey N. Epigenetic therapies for non-oncology indications. Drug Discov Today. 2010;15:1008-14. https://doi.org/10.1016/j.drudis.2010.10.006
  38. Grayson DR, Kundakovic M, Sharma RP. Is there a future for histone deacetylase inhibitors in the pharmacotherapy of psychiatric disorders. Mol Pharmacol. 2010;77:126-35. https://doi.org/10.1124/mol.109.061333
  39. Simonini MV, Camargo LM, Dong E, et al. The benzamide MS-275 is a potent, longlasting brain region-selective inhibitor of histone deacetylases. Proc Natl Acad Sci USA. 2006;103:1587-92. https://doi.org/10.1073/pnas.0510341103
  40. Covington HE, Maze I, LaPlant QC, et al. Antidepressant actions of histone deacetylase inhibitors. J Neurosci. 2009;29:11451-60.         
  41. Dinan TG. MicroRNAs as a target for novel antipsychotics: a systematic review of an emerging field. Int J Neuropsychopharmacol. 2010;13:395-404.