DNA Methylation, the Early-life Social Environment and Behavioral Disorders

Overview

Journal J Neurodev Disord

Publisher Biomed Central

Specialties Neurology
Psychiatry

Date 2011 Apr 13

PMID 21484196

Citations 16

Authors

Moshe Szyf

Affiliations

Soon will be listed here.

Abstract

One of the outstanding questions in behavioral disorders is untangling the complex relationship between nurture and nature. Although epidemiological data provide evidence that there is an interaction between genetics (nature) and the social and physical environments (nurture) in a spectrum of behavioral disorders, the main open question remains the mechanism. Emerging data support the hypothesis that DNA methylation, a covalent modification of the DNA molecule that is a component of its chemical structure, serves as an interface between the dynamic environment and the fixed genome. We propose that modulation of DNA methylation in response to environmental cues early in life serves as a mechanism of life-long genome adaptation. Under certain contexts, this adaptation can turn maladaptive resulting in behavioral disorders. This hypothesis has important implications on understanding, predicting, preventing, and treating behavioral disorders including autism that will be discussed.

Citing Articles

DRDs and Brain-Derived Neurotrophic Factor Share a Common Therapeutic Ground: A Novel Bioinformatic Approach Sheds New Light Toward Pharmacological Treatment of Cognitive and Behavioral Disorders.

Papageorgiou L, Kalospyrou E, Papakonstantinou E, Diakou I, Pierouli K, Dragoumani K Adv Exp Med Biol. 2023; 1424:97-115.

PMID: 37486484 DOI: 10.1007/978-3-031-31982-2_11.

Genome-wide profiling of DNA methylome and transcriptome in peripheral blood monocytes for major depression: A Monozygotic Discordant Twin Study.

Zhu Y, Strachan E, Fowler E, Bacus T, Roy-Byrne P, Zhao J Transl Psychiatry. 2019; 9(1):215.

PMID: 31477685 PMC: 6718674. DOI: 10.1038/s41398-019-0550-2.

Associations of monoamine oxidase A gene first exon methylation with sexual abuse and current depression in women.

Checknita D, Ekstrom T, Comasco E, Nilsson K, Tiihonen J, Hodgins S J Neural Transm (Vienna). 2018; 125(7):1053-1064.

PMID: 29600412 PMC: 5999185. DOI: 10.1007/s00702-018-1875-3.

An epigenome-wide association study meta-analysis of educational attainment.

Karlsson Linner R, Marioni R, Rietveld C, Simpkin A, Davies N, Watanabe K Mol Psychiatry. 2017; 22(12):1680-1690.

PMID: 29086770 PMC: 6372242. DOI: 10.1038/mp.2017.210.

DNA methylation patterns of behavior-related gene promoter regions dissect the gray wolf from domestic dog breeds.

Banlaki Z, Cimarelli G, Viranyi Z, Kubinyi E, Sasvari-Szekely M, Ronai Z Mol Genet Genomics. 2017; 292(3):685-697.

PMID: 28321510 DOI: 10.1007/s00438-017-1305-5.

References

McGowan P, Sasaki A, DAlessio A, Dymov S, Labonte B, Szyf M . Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci. 2009; 12(3):342-8. PMC: 2944040. DOI: 10.1038/nn.2270. View

Weaver I, Cervoni N, Champagne F, DAlessio A, Sharma S, Seckl J . Epigenetic programming by maternal behavior. Nat Neurosci. 2004; 7(8):847-54. DOI: 10.1038/nn1276. View

Wade P, Gegonne A, Jones P, Ballestar E, Aubry F, Wolffe A . Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation. Nat Genet. 1999; 23(1):62-6. DOI: 10.1038/12664. View

Levitt P, Campbell D . The genetic and neurobiologic compass points toward common signaling dysfunctions in autism spectrum disorders. J Clin Invest. 2009; 119(4):747-54. PMC: 2662567. DOI: 10.1172/JCI37934. View

Power C, Jefferis B, Manor O, Hertzman C . The influence of birth weight and socioeconomic position on cognitive development: Does the early home and learning environment modify their effects?. J Pediatr. 2006; 148(1):54-61. DOI: 10.1016/j.jpeds.2005.07.028. View

Fujita H, Fujii R, Aratani S, Amano T, Fukamizu A, Nakajima T . Antithetic effects of MBD2a on gene regulation. Mol Cell Biol. 2003; 23(8):2645-57. PMC: 152551. DOI: 10.1128/MCB.23.8.2645-2657.2003. View

Barreto G, Schafer A, Marhold J, Stach D, Swaminathan S, Handa V . Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature. 2007; 445(7128):671-5. DOI: 10.1038/nature05515. View

Oberlander T, Weinberg J, Papsdorf M, Grunau R, Misri S, Devlin A . Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics. 2008; 3(2):97-106. DOI: 10.4161/epi.3.2.6034. View

Fuso A, Ferraguti G, Grandoni F, Ruggeri R, Scarpa S, Strom R . Early demethylation of non-CpG, CpC-rich, elements in the myogenin 5'-flanking region: a priming effect on the spreading of active demethylation. Cell Cycle. 2010; 9(19):3965-76. PMC: 3047754. DOI: 10.4161/cc.9.19.13193. View

10.

Yoder J, Walsh C, Bestor T . Cytosine methylation and the ecology of intragenomic parasites. Trends Genet. 1997; 13(8):335-40. DOI: 10.1016/s0168-9525(97)01181-5. View

11.

Detich N, Hamm S, Just G, Knox J, Szyf M . The methyl donor S-Adenosylmethionine inhibits active demethylation of DNA: a candidate novel mechanism for the pharmacological effects of S-Adenosylmethionine. J Biol Chem. 2003; 278(23):20812-20. DOI: 10.1074/jbc.M211813200. View

12.

DAlessio A, Szyf M . Epigenetic tête-à-tête: the bilateral relationship between chromatin modifications and DNA methylation. Biochem Cell Biol. 2006; 84(4):463-76. DOI: 10.1139/o06-090. View

13.

Roth T, Lubin F, Funk A, Sweatt J . Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol Psychiatry. 2009; 65(9):760-9. PMC: 3056389. DOI: 10.1016/j.biopsych.2008.11.028. View

14.

Hamm S, Just G, Lacoste N, Moitessier N, Szyf M, Mamer O . On the mechanism of demethylation of 5-methylcytosine in DNA. Bioorg Med Chem Lett. 2007; 18(3):1046-9. DOI: 10.1016/j.bmcl.2007.12.027. View

15.

Mill J, Tang T, Kaminsky Z, Khare T, Yazdanpanah S, Bouchard L . Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. Am J Hum Genet. 2008; 82(3):696-711. PMC: 2427301. DOI: 10.1016/j.ajhg.2008.01.008. View

16.

Kriaucionis S, Heintz N . The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science. 2009; 324(5929):929-30. PMC: 3263819. DOI: 10.1126/science.1169786. View

17.

Razin A, Cedar H . Distribution of 5-methylcytosine in chromatin. Proc Natl Acad Sci U S A. 1977; 74(7):2725-8. PMC: 431263. DOI: 10.1073/pnas.74.7.2725. View

18.

Kucharski R, Maleszka J, Foret S, Maleszka R . Nutritional control of reproductive status in honeybees via DNA methylation. Science. 2008; 319(5871):1827-30. DOI: 10.1126/science.1153069. View

19.

Li E, Bestor T, Jaenisch R . Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell. 1992; 69(6):915-26. DOI: 10.1016/0092-8674(92)90611-f. View

20.

Szyf M . Towards a pharmacology of DNA methylation. Trends Pharmacol Sci. 2001; 22(7):350-4. DOI: 10.1016/s0165-6147(00)01713-2. View