A systematic review of neuroimaging epigenetic research: calling for an increased focus on development

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 (85%), employed a candidate-gene approach (67%), and examined DNAm-brain associations in the context of health and behavioral outcomes (75%). 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.

The Role of Hydrogen Sulfide (H2S) in Epigenetic Regulation of Neurodegenerative Diseases: A Systematic Review

“…For instance, studies have shown altered DNA methylation patterns in genes associated with amyloid-beta processing and tau phosphorylation in Alzheimer’s disease (AD) [ 122 ]. Similarly, in Parkinson’s disease (PD) [ 123 ], dysregulated DNA methylation has been observed in genes linked to mitochondrial function, dopamine signaling, and neuroinflammation [ 124 ].…”

The peripheral epigenome predicts white matter volume contingent on developmental stage: An ECHO study

“…The existing few studies in the field of neuroimaging epigenetics have widely focused on adult and clinical populations. A 2023 review published in Biological Psychiatry reported that only 21% of neuroimaging epigenetic studies explored developmental cohorts, and only 5% in childhood 11 . Even fewer neuroimaging epigenetic studies in developmental cohorts consider typical development; most examine environmental associations or clinical samples 11 .…”

“…A 2023 review published in Biological Psychiatry reported that only 21% of neuroimaging epigenetic studies explored developmental cohorts, and only 5% in childhood 11 . Even fewer neuroimaging epigenetic studies in developmental cohorts consider typical development; most examine environmental associations or clinical samples 11 . Additionally, only ten longitudinal cohorts that track both DNAm and MRI in pediatric populations were noted in a systematic review 10 .…”

DNA methylation at birth and lateral ventricular volume in childhood: a neuroimaging epigenetics study

“…Most studies to date have associated DNAm with schizophrenia using postmortem brain tissues, which cannot inform on developmental processes in living individuals (Lancaster, Morris, & Connelly, 2018). Neuroimaging epigenetics can help to bridge this gap by combining DNAm from peripheral tissues with in vivo brain imaging techniques, such as structural magnetic resonance imaging (MRI; Walton et al., 2023; Wheater et al., 2020). This approach could provide novel insights into epigenetic processes contributing to brain features associated with schizophrenia risk, such as LVV enlargement.…”