Şizofrenide Epigenetik Bakış Açısı: DNA Metilasyon Modelleri

Yıl 2022, Cilt: 31 Sayı: 3, 204 - 212, 30.09.2022

Ezgi Karaaslan , Şükrü Kartalcı , Ceren Acar

https://doi.org/10.17827/aktd.1096901

Cited By: 1

Öz

Şizofreni, sanrılar, halüsinasyonlar ve çeşitli davranış bozuklukları ile karakterize bir zihinsel bozukluktur. Dünya nüfusunun yaklaşık %1'ini etkileyen şizofreni sadece hastaları değil toplumun diğer üyelerini de etkilemektedir. Hastalığın etiyolojisinde genetik ve çevresel faktörler rol oynamaktadır.
Genetik, nörogelişimsel bozukluklar, ilaç kullanımı, şehir hayatı, tek başına veya birlikte hastalığa neden olan faktörler sayılabilir. Son yıllarda artan araştırmalara rağmen şizofreni oluşumuna neden olan faktörler tam olarak aydınlatılamamıştır ve daha fazla araştırmaya ihtiyaç vardır. Genetik faktörlerin şizofreni için risk faktörleri olmasına rağmen, bazı çevresel faktörlerin hastalığın ortaya çıkışını etkilediği düşünülmektedir. Epigenetik mekanizmalar, DNA'nın nükleotid dizisini değiştirmeden gen fonksiyonlarını düzenler. DNA metilasyonu şizofreni ile ilişkilidir ve birçok şizofreni aday geninde metilasyon durumu çalışmaları yapılmıştır. DNA metilasyon durumlarının incelenmesi psikiyatrik araştırmalara önemli katkı sağlayacaktır.
Bu derlemede şizofreni ile ilgili DNA metilasyon çalışmalarından elde edilen global veri tabanlarında yayınlanan veriler özetlenmiş ve şizofrenideki önemi kısaca tartışılmıştır.

Anahtar Kelimeler

şizofreni, epigenetik, çevresel faktörler, DNA metilasyonu

Destekleyen Kurum

İnönü Üniversitesi

Proje Numarası

FYL-2020-2241

Teşekkür

Yazarlar desteklerinden dolayı İnönü Üniversitesi Bilimsel Araştırma Projeleri Birimi'ne teşekkür etmektedirler.

Epigenetic Perspective in Schizophrenia: DNA Methylation Patterns

Öz

Schizophrenia is a mental disorder characterized by delusions, hallucinations and various behavioral disorders. Affecting approximately 1% of the world's population, schizophrenia not only affects patients, but also other members of the society. Genetic and environmental factors play roles in the etiology of the disorder.
Genetics, neurodevelopmental disorder, drug use, urban life, alone or together can be counted as the factors that cause the disorder. Despite increasing studies in recent years, the factors causing the formation of schizophrenia have not been fully clarified and more research is needed. Although genetic factors are risk factors for schizophrenia, it is thought that some environmental factors affect the emergence of the disorder. Epigenetic mechanisms regulate gene functions without changing the nucleotide sequence of DNA. DNA methylation is associated with schizophrenia, and methylation status studies have been conducted in many schizophrenia candidate genes. Examination of DNA methylation states will contribute significantly to psychiatric research.
In this review, data published in global databases obtained from DNA methylation studies related with schizophrenia are summarized and their importance in schizophrenia is briefly discussed.

Anahtar Kelimeler

schizophrenia, epigenetics, environmental factors, DNA methylation

Proje Numarası

FYL-2020-2241

Kaynakça

• REFERENCES 1. Andreasen NC. Schizophrenia: the fundamental questions. Brain Res Brain Res Rev. Mar 2000;31(2-3):106-112.
• 2. Wong AH, Van Tol HH. Schizophrenia: from phenomenology to neurobiology. Neurosci Biobehav Rev. May 2003;27(3):269-306.
• 3. Winship IR, Dursun SM, Baker GB, et al. An Overview of Animal Models Related to Schizophrenia. Can J Psychiatry. Jan 2019;64(1):5-17.
• 4. Moran P, Stokes J, Marr J, et al. Gene x Environment Interactions in Schizophrenia: Evidence from Genetic Mouse Models. Neural Plast. 2016;2016:2173748.
• 5. Modai S, Shomron N. Molecular Risk Factors for Schizophrenia. Trends Mol Med. Mar 2016;22(3):242-253.
• 6. Andreasen NC. Schizophrenia: the fundamental questions. Brain Research Reviews. Mar 2000;31(2-3):106-112.
• 7. Khavari B, Cairns MJ. Epigenomic Dysregulation in Schizophrenia: In Search of Disease Etiology and Biomarkers. Cells. Aug 5 2020;9(8).
• 8. Alelu-Paz R, Gonzalez-Corpas A, Ashour N, et al. DNA methylation pattern of gene promoters of major neurotransmitter systems in older patients with schizophrenia with severe and mild cognitive impairment. International Journal of Geriatric Psychiatry. Jun 2015;30(6):558-565.
• 9. Hoffman GE, Bendl J, Voloudakis G, et al. CommonMind Consortium provides transcriptomic and epigenomic data for Schizophrenia and Bipolar Disorder. Sci Data. Sep 24 2019;6(1):180.
• 10. Maric NP, Svrakic DM. Why schizophrenia genetics needs epigenetics: a review. Psychiatr Danub. Mar 2012;24(1):2-18.
• 11. Picchioni MM, Murray RM. Schizophrenia. BMJ. Jul 14 2007;335(7610):91-95.
• 12. Weiser M, Davidson M, Noy S. Comments on risk for schizophrenia. Schizophr Res. Nov 1 2005;79(1):15-21.
• 13. O'Connell G, Lawrie SM, McIntosh AM, Hall J. Schizophrenia risk genes: Implications for future drug development and discovery. Biochem Pharmacol. Jun 15 2011;81(12):1367-1373.
• 14. Janoutova J, Janackova P, Sery O, et al. Epidemiology and risk factors of schizophrenia. Neuro Endocrinol Lett. 2016;37(1):1-8.
• 15. Messias EL, Chen CY, Eaton WW. Epidemiology of schizophrenia: review of findings and myths. Psychiatr Clin North Am. Sep 2007;30(3):323-338.
• 16. Pries LK, Guloksuz S, Kenis G. DNA Methylation in Schizophrenia. Adv Exp Med Biol. 2017;978:211-236.
• 17. Cromby J, Chung E, Papadopoulos D, Talbot C. Reviewing the epigenetics of schizophrenia. J Ment Health. Feb 2019;28(1):71-79.
• 18. Zhang G, Pradhan S. Mammalian epigenetic mechanisms. IUBMB Life. Apr 2014;66(4):240-256.
• 19. Wei JW, Huang K, Yang C, Kang CS. Non-coding RNAs as regulators in epigenetics (Review). Oncol Rep. Jan 2017;37(1):3-9.
• 20. Teroganova N, Girshkin L, Suter CM, Green MJ. DNA methylation in peripheral tissue of schizophrenia and bipolar disorder: a systematic review. BMC Genet. Jan 25 2016;17:27.
• 21. Dahl C, Guldberg P. DNA methylation analysis techniques. Biogerontology. 2003;4(4):233-250.
• 22. Nestler EJ, Pena CJ, Kundakovic M, Mitchell A, Akbarian S. Epigenetic Basis of Mental Illness. Neuroscientist. Oct 2016;22(5):447-463.
• 23. Tajima S, Suetake I, Takeshita K, Nakagawa A, Kimura H. Domain Structure of the Dnmt1, Dnmt3a, and Dnmt3b DNA Methyltransferases. Adv Exp Med Biol. 2016;945:63-86.
• 24. Chen ZY, Zhang Y. Role of Mammalian DNA Methyltransferases in Development. In: Kornberg RD, ed. Annual Review of Biochemistry, Vol 89. Vol 892020:135-158.
• 25. Numata S, Ye T, Herman M, Lipska BK. DNA methylation changes in the postmortem dorsolateral prefrontal cortex of patients with schizophrenia. Front Genet. 2014;5:280.
• 26. Gejman PV, Sanders AR, Kendler KS. Genetics of schizophrenia: new findings and challenges. Annu Rev Genomics Hum Genet. 2011;12:121-144.
• 27. Kumar A, Dalan E, Carless MA. Analysis of DNA methylation using pyrosequencing. Epigenetics Methods: Elsevier; 2020:37-62.
• 28. Feng L, Lou J. DNA Methylation Analysis. Methods Mol Biol. 2019;1894:181-227.
• 29. Shen L, Waterland RA. Methods of DNA methylation analysis. Curr Opin Clin Nutr Metab Care. Sep 2007;10(5):576-581.
• 30. Coffee B. Methylation-specific PCR. Curr Protoc Hum Genet. Apr 2009;Chapter 10:Unit 10 16.
• 31. Eads CA, Laird PW. Combined bisulfite restriction analysis (COBRA). Methods Mol Biol. 2002;200:71-85.
• 32. Moelans CB, Atanesyan L, Savola SP, van Diest PJ. Methylation-Specific Multiplex Ligation-Dependent Probe Amplification (MS-MLPA). Methods Mol Biol. 2018;1708:537-549.
• 33. Campan M, Weisenberger DJ, Trinh B, Laird PW. MethyLight. Methods Mol Biol. 2009;507:325-337.
• 34. Liu C, Jiao C, Wang K, Yuan N. DNA Methylation and Psychiatric Disorders. Prog Mol Biol Transl Sci. 2018;157:175-232.
• 35. Smigielski L, Jagannath V, Rossler W, Walitza S, Grunblatt E. Epigenetic mechanisms in schizophrenia and other psychotic disorders: a systematic review of empirical human findings. Mol Psychiatry. Aug 2020;25(8):1718-1748.
• 36. Zamanpoor M. Schizophrenia in a genomic era: a review from the pathogenesis, genetic and environmental etiology to diagnosis and treatment insights. Psychiatr Genet. Feb 2020;30(1):1-9.
• 37. Labrie V, Pai S, Petronis A. Epigenetics of major psychosis: progress, problems and perspectives. Trends Genet. Sep 2012;28(9):427-435.
• 38. Shorter KR, Miller BH. Epigenetic mechanisms in schizophrenia. Prog Biophys Mol Biol. Jul 2015;118(1-2):1-7.
• 39. Richetto J, Meyer U. Epigenetic Modifications in Schizophrenia and Related Disorders: Molecular Scars of Environmental Exposures and Source of Phenotypic Variability. Biol Psychiatry. Feb 1 2021;89(3):215-226.
• 40. Ovenden ES, McGregor NW, Emsley RA, Warnich L. DNA methylation and antipsychotic treatment mechanisms in schizophrenia: Progress and future directions. Prog Neuropsychopharmacol Biol Psychiatry. Feb 2 2018;81:38-49.
• 41. Chuan HK. Differential DNA Methylation and Network Analysis in Schizophrenia. Computational Epigenetics and Diseases: Elsevier; 2019:121-129.
• 42. Punzi G, Bharadwaj R, Ursini G. Neuroepigenetics of Schizophrenia. Prog Mol Biol Transl Sci. 2018;158:195-226.
• 43. Grayson DR, Guidotti A. The dynamics of DNA methylation in schizophrenia and related psychiatric disorders. Neuropsychopharmacology. Jan 2013;38(1):138-166.
• 44. Veldic M, Caruncho HJ, Liu WS, et al. DNA-methyltransferase 1 mRNA is selectively overexpressed in telencephalic GABAergic interneurons of schizophrenia brains. Proc Natl Acad Sci U S A. Jan 6 2004;101(1):348-353.
• 45. Iwamoto K, Bundo M, Yamada K, et al. DNA methylation status of SOX10 correlates with its downregulation and oligodendrocyte dysfunction in schizophrenia. J Neurosci. Jun 1 2005;25(22):5376-5381.
• 46. Abdolmaleky HM, Cheng KH, Faraone SV, et al. Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder. Human Molecular Genetics. Nov 2006;15(21):3132-3145.
• 47. Nohesara S, Ghadirivasfi M, Mostafavi S, et al. DNA hypomethylation of MB-COMT promoter in the DNA derived from saliva in schizophrenia and bipolar disorder. J Psychiatr Res. Nov 2011;45(11):1432-1438.
• 48. Dempster EL, Mill J, Craig IW, Collier DA. The quantification of COMT mRNA in post mortem cerebellum tissue: diagnosis, genotype, methylation and expression. BMC Med Genet. Feb 16 2006;7:10.
• 49. Huang HS, Akbarian S. GAD1 mRNA expression and DNA methylation in prefrontal cortex of subjects with schizophrenia. PLoS One. Aug 29 2007;2(8):e809.
• 50. Hu TM, Chen SJ, Hsu SH, Cheng MC. Functional analyses and effect of DNA methylation on the EGR1 gene in patients with schizophrenia. Psychiatry Res. May 2019;275:276-282.
• 51. Hu TM, Hsu SH, Tsai SM, Cheng MC. DNA methylation analysis of the EGR3 gene in patients of schizophrenia. Psychiatry Res. May 2017;251:115-117.
• 52. Wang L, Jiang W, Lin Q, Zhang Y, Zhao C. DNA methylation regulates gabrb2 mRNA expression: developmental variations and disruptions in l-methionine-induced zebrafish with schizophrenia-like symptoms. Genes Brain Behav. Nov 2016;15(8):702-710.
• 53. Ikegame T, Bundo M, Sunaga F, et al. DNA methylation analysis of BDNF gene promoters in peripheral blood cells of schizophrenia patients. Neurosci Res. Dec 2013;77(4):208-214.
• 54. Copoglu US, Igci M, Bozgeyik E, et al. DNA Methylation of BDNF Gene in Schizophrenia. Medical Science Monitor. Feb 2016;22:397-402.
• 55. Carrard A, Salzmann A, Malafosse A, Karege F. Increased DNA methylation status of the serotonin receptor 5HTR1A gene promoter in schizophrenia and bipolar disorder. Journal of Affective Disorders. Aug 2011;132(3):450-453.
• 56. Nishioka M, Bundo M, Koike S, et al. Comprehensive DNA methylation analysis of peripheral blood cells derived from patients with first-episode schizophrenia. J Hum Genet. Feb 2013;58(2):91-97.
• 57. Mill J, Tang T, Kaminsky Z, et al. Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. Am J Hum Genet. Mar 2008;82(3):696-711.
• 58. Ikegame T, Bundo M, Okada N, et al. Promoter Activity-Based Case-Control Association Study on SLC6A4 Highlighting Hypermethylation and Altered Amygdala Volume in Male Patients With Schizophrenia. Schizophr Bull. Dec 1 2020;46(6):1577-1586.
• 59. Gao J, Yi H, Tang X, et al. DNA Methylation and Gene Expression of Matrix Metalloproteinase 9 Gene in Deficit and Non-deficit Schizophrenia. Front Genet. 2018;9:646.
• 60. Sugawara H, Murata Y, Ikegame T, et al. DNA methylation analyses of the candidate genes identified by a methylome-wide association study revealed common epigenetic alterations in schizophrenia and bipolar disorder. Psychiatry Clin Neurosci. Apr 2018;72(4):245-254.
• 61. Dyrvig M, Qvist P, Lichota J, et al. DNA Methylation Analysis of BRD1 Promoter Regions and the Schizophrenia rs138880 Risk Allele. PLoS One. 2017;12(1):e0170121.
• 62. Zhang AP, Yu J, Liu JX, et al. The DNA methylation profile within the 5'-regulatory region of DRD2 in discordant sib pairs with schizophrenia. Schizophr Res. Feb 2007;90(1-3):97-103.
• 63. Kordi-Tamandani DM, Dahmardeh N, Torkamanzehi A. Evaluation of hypermethylation and expression pattern of GMR2, GMR5, GMR8, and GRIA3 in patients with schizophrenia. Gene. Feb 15 2013;515(1):163-166.
• 64. Kordi-Tamandani DM, Sahranavard R, Torkamanzehi A. DNA methylation and expression profiles of the brain-derived neurotrophic factor (BDNF) and dopamine transporter (DAT1) genes in patients with schizophrenia. Mol Biol Rep. Dec 2012;39(12):10889-10893.
• 65. Snijders C, Bassil KC, de Nijs L. Methodologies of Neuroepigenetic Research: Background, Challenges and Future Perspectives. Prog Mol Biol Transl Sci. 2018;158:15-27.