A systematic review of neuroimaging epigenetic research: Calling for an increased focus on development
Year: 2020
Type: preprint
Study design: Systematic Review
Abstract: Epigenetic mechanisms, such as DNA methylation (DNAm), have gained increasing attention as potential biomarkers and mechanisms underlying risk for neurodevelopmental, psychiatric and other brain-based disorders. Yet, surprisingly little is known about the extent to which DNAm is linked to individual differences in the brain itself, and how these associations may unfold across development – a time of life when many of these disorders emerge. Here, we systematically review evidence from the nascent field of Neuroimaging Epigenetics, combining structural or functional neuroimaging measures with DNAm, and the extent to which the developmental period (birth to adolescence) is represented in these studies. We identified 111 articles published between 2011–2021, out of which only a minority (21%) included samples under 18 years of age. Most studies were cross-sectional, employed a candidate-gene approach, and examined DNAm-brain associations in the context of health and behavioral outcomes. Nearly half incorporated genetic data, and a fourth investigated environmental influences. Overall, studies support a link between peripheral DNAm and brain imaging measures, but there is little consistency in specific findings and it remains unclear whether DNAm markers present a cause, correlate or consequence of brain alterations. Overall, there is large heterogeneity in sample characteristics, peripheral tissue and brain outcome examined as well as the methods used. Sample sizes were generally low to moderate (median nall=98, ndevelopmental=80), and attempts at replication or meta-analysis were rare. Based on the strengths and weaknesses of existing studies, we propose three recommendations on how advance the field of Neuroimaging Epigenetics. We advocate for: (1) a greater focus on developmentally oriented research (i.e. pre-birth to adolescence); 2) the analysis of large, prospective, pediatric cohorts with repeated measures of DNAm and imaging to assess directionality; and (3) collaborative, interdisciplinary science to identify robust signals, triangulate findings and enhance translational potential.
Authors: Esther Walton, Vilte Baltramonaityte, Vince D Calhoun, Bas Heijmans, Paul Thompson, Charlotte Cecil
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Alzheimer's Association, European Commission, National Institutes of Health, Medical Research Council, Economic and Social Research Council, National Institute on Aging, National Institute of Mental Health, National Institute of Biomedical Imaging and Bioengineering
Awards: G106558557, G1157805208, ENIGMA-SD: Understanding Sex Differences in Global Mental Health through ENIGMA, ENIGMA World Aging Center, G2531818126, Running in the FAMILY - Understanding and predicting the intergenerational transmission of mental illness, G3239377387, G341899895, Cohort and Longitudinal Studies Enhancement Resources (CLOSER), G434337789, G4364139308, G4421633565, Understanding, predicting, and treating depression in pregnancy to improve mothers and offspring mental health outcomes, G5508677496, Causative mechanisms & integrative models linking early-life-stress to psycho-cardio-metabolic multi-morbidity, ENIGMA Center for Worldwide Medicine, Imaging & Genomics, Dynamic imaging-genomic models for characterizing and predicting psychosis and mood disorders, CREST Center for Dynamic Multiscale and Multimodal Brain Mapping Over The Lifespan [D-MAP], G6653948526, G7483196170, G8045000093, Laboratory of Neuro Imaging Resource (LONIR), G8614242721, G9000210308, Genomic Architecture of Functional Brain Networks in PTSD, Childhood adversity, DNA methylation, and psychopathology symptoms: A longitudinal study of sensitive periods and chrono-epigenetics
OpenAlex ID: W3161451535