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Updated: Jan 29, 2026
Optimized Analysis of DNA Methylation and Gene Expression from Small, Anatomically-defined Areas of the Brain
Published on: July 12, 2012
Brain-derived neurotrophic factor DNA methylation mediates the association between neighborhood disadvantage and
Jo Wrigglesworth1, Joanne Ryan2, Nandita Vijayakumar3
1Melbourne 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.
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.
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