Annual Research Review: DNA methylation as a mediator in the association between risk exposure and child and adolescent psychopathology

Edward D. Barker1, Esther Walton1,2, Charlotte A. M. Cecil1
1Department of Psychology, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK
2Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK

Tóm tắt

Background

DNA methylation (DNAm) is a potential mechanism for propagating the effects of environmental exposures on child and adolescent mental health. In recent years, this field has experienced steady growth.

Methods

We provide a strategic review of the current child and adolescent literature to evaluate evidence for a mediating role of DNAm in the link between environmental risks and psychopathological outcomes, with a focus on internalising and externalising difficulties.

Results

Based on the studies presented, we conclude that there is preliminary evidence to support that (a) environmental factors, such as diet, neurotoxic exposures and stress, influence offspring DNAm, and that (b) variability in DNAm, in turn, is associated with child and adolescent psychopathology. Overall, very few studies have examined DNAm in relation to both exposures and outcomes, and almost all analyses have been correlational in nature.

Conclusions

DNAm holds potential as a biomarker indexing both environmental risk exposure and vulnerability for child psychopathology. However, the extent to which it may represent a causal mediator is not clear. In future, collection of prospective risk exposure, DNAm and outcomes – as well as functional characterisation of epigenetic findings – will assist in determining the role of DNAm in the link between risk exposure and psychopathology.

Từ khóa


Tài liệu tham khảo

10.1186/1471-2164-15-487

10.1126/science.1108190

10.1017/S0033291712002450

Barker E.D., A methylome‐wide association study of trajectories of oppositional defiant behaviors and biological overlap with attention deficit hyperactivity disorder, Child Development

Barker E.D., The Wiley handbook of disruptive and impulse‐control disorders

10.1192/bjp.bp.113.129486

10.1176/appi.ajp.2009.08121770

10.1002/ajmg.b.31028

10.1186/1471-2105-14-353

10.1093/ije/dyr147

10.1038/npp.2015.247

10.1164/rccm.200901-0135OC

10.1371/journal.pone.0107653

10.1080/15592294.2015.1046026

10.1038/mp.2014.95

10.1016/j.jpsychires.2016.09.010

10.1111/jcpp.12213

10.1017/S095457941700092X

10.1038/tp.2016.247

10.1007/s40429-015-0072-9

10.3945/an.110.1004

10.1017/S0954579400007318

10.1017/S0954579413000497

10.1111/cdev.12391

10.1007/s00787-016-0828-3

10.1186/gb-2012-13-6-r43

10.1016/j.biopsych.2014.04.013

10.1080/15622975.2016.1224928

10.1017/S0954579416000055

10.1111/j.1467-8624.2011.01641.x

10.1186/s13059-016-0926-z

10.2337/db10-0979

10.1371/journal.pone.0086822

10.1038/nn.4182

10.1093/hmg/ddm010

10.1073/pnas.0806560105

10.1007/s10519-015-9721-y

10.1016/S0168-9525(97)01219-5

10.1016/j.jpsychires.2013.03.009

10.1186/1471-2458-11-46

10.1038/ng1089

10.1289/ehp.1205412

10.1038/ng.286

10.1016/j.psyneuen.2015.04.012

10.1016/j.neubiorev.2013.03.020

10.1038/tp.2016.95

10.2217/epi.15.102

10.1093/aje/kwk030

Lawlor D.A., 2017, Triangulation in aetiological epidemiology, International Journal of Epidemiology, 45, 1866

10.1093/hmg/ddu284

10.1016/j.neuroscience.2013.07.069

10.1038/nn.2270

10.1371/journal.pone.0033290

10.1186/gb-2014-15-5-r73

10.1111/j.1467-8624.2009.01381.x

Meehan A.J. Cecil C.A.M. Maughan B. Relton C.L. Gaunt T.R. McArdle W. &Barker E.D.Epigenetic correlates of low prosocial behavior: A prospective genome‐wide study unpublished data.

10.1016/j.jpsychires.2013.10.017

10.1038/nrg3405

10.1176/appi.ajp.2015.15091171

10.1111/jcpp.12000

10.1016/j.ymeth.2014.08.011

10.1371/journal.pone.0126903

10.1038/tp.2014.140

10.1017/S0954579411000605

10.1002/ajhb.22679

10.4161/epi.3.2.6034

10.1038/pr.2013.95

10.1192/bjp.180.6.502

10.1017/S0033291712002784

10.1111/cdev.12484

10.1017/S003329171500094X

10.1016/j.biopsych.2016.03.2100

10.1002/ajmg.b.30778

10.1186/s13059-016-1066-1

10.1016/j.beem.2012.03.010

10.1371/journal.pone.0089839

10.1371/journal.pone.0069481

10.1093/ije/dyr233

10.1093/ije/dyv072

10.1016/j.earlhumdev.2014.08.023

10.1093/hmg/ddu739

10.1111/jcpp.12589

10.1080/15592294.2016.1145329

10.1038/tp.2014.83

10.1176/appi.ajp.2014.14030382

10.2217/epi.15.2

10.4161/epi.21493

10.1093/ije/dyv042

10.1016/j.biopsych.2016.08.032

10.1038/nrd4580

10.1038/mp.2015.224

10.1038/nrg.2016.45

10.1101/gr.171439.113

10.1038/ncomms6592

10.1016/j.biopsych.2014.11.022

10.1111/gbb.12147

1957 Allen & Unwin London C.H. Waddington The strategy of the genes: A discussion of some aspects of theoretical biology

10.1111/jcpp.12740

10.1093/schbul/sbv074

10.1038/mp.2016.85

10.1371/journal.pone.0039501

10.1038/nn1276

10.1016/j.jaac.2013.12.025

10.1111/jcpp.12457

10.1016/j.jpsychires.2015.03.006

10.1016/j.amepre.2012.10.012

10.1016/j.biopsych.2015.08.005

10.1016/S0006-3223(98)00276-5

10.1017/S0007114514002827