Brain-derived neurotrophic factor DNA methylation mediates the association between neighborhood disadvantage and adolescent brain structure

Jo Wrigglesworth; Joanne Ryan; Nandita Vijayakumar; Sarah Whittle

doi:10.1016/j.pscychresns.2018.12.012

Brain-derived neurotrophic factor DNA methylation mediates the association between neighborhood disadvantage and adolescent brain structure

Psychiatry Res Neuroimaging. 2019 Mar 30:285:51-57. doi: 10.1016/j.pscychresns.2018.12.012. Epub 2018 Dec 24.

Authors

Jo Wrigglesworth¹, Joanne Ryan², Nandita Vijayakumar³, Sarah Whittle⁴

Affiliations

¹ Melbourne Neuropsychiatry Center, Department of Psychiatry, The University of Melbourne and Melbourne Health, Parkville, Victoria, Australia; Disease Epigenetics, Murdoch Children's Research Institute, The University of Melbourne, Parkville, Victoria, Australia.
² Disease Epigenetics, Murdoch Children's Research Institute, The University of Melbourne, Parkville, Victoria, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
³ Department of Psychology, University of Oregon, Eugene, OR, USA.
⁴ Melbourne Neuropsychiatry Center, Department of Psychiatry, The University of Melbourne and Melbourne Health, Parkville, Victoria, Australia; Melbourne School of Psychological Sciences, The University of Melbourne, Melbourne, Victoria, Australia. Electronic address: swhittle@unimelb.edu.au.

PMID: 30771753
DOI: 10.1016/j.pscychresns.2018.12.012

Abstract

Prior research indicates that socioeconomic disadvantage is associated with prefrontal cortical (PFC) development in childhood and adolescence, however the mechanisms of this link are unclear. This study investigated whether DNA methylation of the brain-derived neurotrophic factor (BDNF, which plays a key role in synaptic plasticity), mediated the association between neighborhood disadvantage and thickness of the PFC in adolescents. Neighborhood disadvantage was measured in 33 adolescents aged 12-13 years using the Socio-Economic Indexes for Areas. Buccal swabs, collected during mid-adolescence (aged 16-18 years), enabled BDNF DNA methylation of the widely studied exon IV promoter region to be measured. Cortical thickness was assessed during late-adolescence (aged 18-20 years) via T1-weighted magnetic resonance imaging (MRI). A significant negative association between disadvantage and BDNF DNA methylation at a specific site of the exon IV promoter was identified. Lower levels of methylation were also significantly associated with greater thickness of the lateral orbitofrontal cortex (lOFC), and right medial OFC. Lower levels of DNA methylation at this site also mediated associations between higher disadvantage and thinner bilateral lOFC thickness. These novel findings give insight into a potential biological mechanism that could further our understanding as to why brain development is affected by varying environmental exposures.

Keywords: Brain derived neurotrophic factor; Cortical thickness; DNA methylation; Epigenetics; Prefrontal cortex; Socioeconomic disadvantage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Brain-Derived Neurotrophic Factor / genetics
Brain-Derived Neurotrophic Factor / metabolism*
Child
DNA Methylation / physiology*
Female
Humans
Longitudinal Studies
Magnetic Resonance Imaging / methods
Male
Prefrontal Cortex / diagnostic imaging*
Prefrontal Cortex / metabolism*
Promoter Regions, Genetic / genetics
Residence Characteristics*
Vulnerable Populations* / psychology
Young Adult

Substances

Brain-Derived Neurotrophic Factor
BDNF protein, human