Epigenetics applied to child and adolescent mental health: Progress, challenges and opportunities

Cecil, Charlotte A.M.; Neumann, Alexander; Walton, Esther

doi:10.1002/jcv2.12133

Cited by 12 publications

(7 citation statements)

References 149 publications

(140 reference statements)

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“…We thus highlight the significance of epigenetic timing since, as mentioned above, alterations in epigenetic markers detectable at early stages can be transient and not measurable later in disease progression or life 48 , 74 . These timing effects could also explain some inconsistent findings reported in the literature 75 . We thus believe that the identification of early epigenetic biomarkers would be of relevance in order to predict disease trajectories and eventually choose a suitable therapy.…”

Section: Discussionmentioning

confidence: 87%

Mild internet use is associated with epigenetic alterations of key neurotransmission genes in salivary DNA of young university students

Annunzi,

Cannito,

Bellia

et al. 2023

Sci Rep

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The potentially problematic use of the Internet is a growing concern worldwide, which causes and consequences are not completely understood yet. The neurobiology of Internet addiction (IA) has attracted much attention in scientific research, which is now focusing on identifying measurable biological markers. Aim of this study was to investigate epigenetic and genetic regulation of oxytocin receptor (OXTR), dopamine transporter (DAT1) and serotonin transporter (SERT) genes using DNA obtained from saliva samples of young university students: the Internet Addiction Test (IAT) was administered to evaluate the potential existence and intensity of IA. Significant changes in DNA methylation levels at OXTR, DAT1 and SERT genes were observed in the 30 < IAT < 49 group (mild-risk internet users) compared to the IAT < 29 subjects (complete control of internet use) and IAT > 50 subjects (considered as moderately addicted). Moreover, epigenetic markers were significantly correlated, either directly (for OXTR and DAT1) or inversely (OXTR and DAT1 versus SERT), to the psychometric properties. Our data confirmed the association of OXTR, DAT1 and SERT genes in processes related to behavioural addictions and might be of relevance to suggest possible biological predictors of altered behaviours and the eventual vulnerability to develop an IA. Different other genetic pathways have been suggested to play a role in IA and research is ongoing to better define them, in order to help in the early diagnosis as well as in the development of new potential treatments.

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Section: Discussionmentioning

confidence: 87%

Mild internet use is associated with epigenetic alterations of key neurotransmission genes in salivary DNA of young university students

Annunzi,

Cannito,

Bellia

et al. 2023

Sci Rep

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“…Racial marginalization and low socioeconomic status has been associated with more advanced and faster biological aging as measured in DNAm in both adults and children, and, in adults, these differences in biological aging partially account for health disparities between and within racial groups (Del Toro et al, 2022; Oblak et al, 2021; Raffington et al, 2021; Sugden et al, 2023). A few studies have found DNAm measures of biological aging to be associated with mental health (Cecil et al, 2023; Oblak et al, 2021; Raffington, Tanksley, et al, 2023). Yet, previous research has largely been cross-sectional in design and, thus, does not address the dynamic interplay between racialization, mental health, and biological aging.…”

Section: Introductionmentioning

confidence: 99%

Linked emergence of racial disparities in mental health and epigenetic biological aging across childhood and adolescence

Aikins,

Willems,

Mitchell

et al. 2024

Preprint

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Marginalization due to structural racism may confer an increased risk for aging-related diseases in part via effects on peoples mental health. Here we leverage a prospective birth cohort study to examine whether the emergence of racial disparities in mental health and DNA-methylation measures of biological aging (i.e., DunedinPACE, GrimAge Acceleration, PhenoAge Acceleration) are linked across childhood and adolescence. We further consider to what extent racial disparities are statistically accounted for by perinatal and postnatal factors in preregistered analyses of N=4,898 participants from the Future of Families & Child Wellbeing Study, of which N=2,039 had repeated saliva DNA methylation at ages 9 and 15 years. We find that racially marginalized children had higher levels of externalizing and internalizing behaviors and diverging longitudinal internalizing slopes. Black compared to White identifying children, children living in more racially segregated neighborhoods, and racially marginalized children more affected by colorism tended to have higher age-9 levels of biological aging and more biological age acceleration over adolescence. Notably, longitudinal increases in internalizing and externalizing behavior were correlated with longitudinal increases in biological aging. While racial and ethnic disparities in mental health were largely statistically accounted for by socioeconomic variables, racial differences in biological aging were often still visible beyond covariate controls. Our findings indicate that racial disparities in mental health and biological aging are linked and emerge early in life. Programs promoting racial health equity must address the psychological and physical impacts of structural racism in children. Comprehensive measures of racism are lacking in current population cohorts.

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“…While making mechanistic inferences about the role of peripheral DNAm in brain‐based phenotypes is challenging (e.g. due to cross‐tissue variability in DNAm), research has increasingly demonstrated the potential of peripheral DNAm as a non‐causal biological marker for disease prediction, stratification, and diagnosis (Cecil, Neumann, & Walton, 2023 ; Min et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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

Luo

Walton

Neumann

et al. 2023

Child Psychology Psychiatry

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BackgroundLateral ventricular volume (LVV) enlargement has been repeatedly linked to schizophrenia; yet, what biological factors shape LVV during early development remain unclear. DNA methylation (DNAm), an essential process for neurodevelopment that is altered in schizophrenia, is a key molecular system of interest.MethodsIn this study, we conducted the first epigenome‐wide association study of neonatal DNAm in cord blood with LVV in childhood (measured using T1‐weighted brain scans at 10 years), based on data from a large population‐based birth cohort, the Generation R Study (N = 840). Employing both probe‐level and methylation profile score (MPS) approaches, we further examined whether epigenetic modifications identified at birth in cord blood are: (a) also observed cross‐sectionally in childhood using peripheral blood DNAm at age of 10 years (Generation R, N = 370) and (b) prospectively associated with LVV measured in young adulthood in an all‐male sample from the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 114).ResultsAt birth, DNAm levels at four CpGs (annotated to potassium channel tetramerization domain containing 3, KCTD3; SHH signaling and ciliogenesis regulator, SDCCAG8; glutaredoxin, GLRX) prospectively associated with childhood LVV after genome‐wide correction; these genes have been implicated in brain development and psychiatric traits including schizophrenia. An MPS capturing a broader epigenetic profile of LVV – but not individual top hits – showed significant cross‐sectional associations with LVV in childhood in Generation R and prospectively associated with LVV in early adulthood within ALSPAC.ConclusionsThis study finds suggestive evidence that DNAm at birth prospectively associates with LVV at different life stages, albeit with small effect sizes. The prediction of MPS on LVV in a childhood sample and an independent male adult sample further underscores the stability and reproducibility of DNAm as a potential marker for LVV. Future studies with larger samples and comparable time points across development are needed to further elucidate how DNAm associates with this clinically relevant brain structure and risk for neuropsychiatric disorders, and what factors explain the identified DNAm profile of LVV at birth.

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Epigenetics applied to child and adolescent mental health: Progress, challenges and opportunities

Cited by 12 publications

References 149 publications

Mild internet use is associated with epigenetic alterations of key neurotransmission genes in salivary DNA of young university students

Mild internet use is associated with epigenetic alterations of key neurotransmission genes in salivary DNA of young university students

Linked emergence of racial disparities in mental health and epigenetic biological aging across childhood and adolescence

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

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