Principles and Challenges of Applying Epigenetic Epidemiology to Psychology

Jones, Meaghan J.; Moore, Sarah R.; Kobor, Michæl S.

doi:10.1146/annurev-psych-122414-033653

Cited by 72 publications

(98 citation statements)

References 146 publications

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“…Further, the best method to correct for interindividual variability in cell type is still highly debated (McGregor Labbe, & Greenwood, 2017) which is further complicated by the lack of well-characterized reference profiles for young child saliva. Regardless, future environmental epigenetics studies will benefit from controlling for this important type of variation (Jones et al, in press). …”

Section: Discussionmentioning

confidence: 99%

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Dynamic stress-related epigenetic regulation of the glucocorticoid receptor gene promoter during early development: The role of child maltreatment

et al. 2017

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Epigenetics processes may play a vital role in the biological embedding of early environmental adversity and the development of psychopathology. Accumulating evidence suggests that maltreatment is linked to methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), which is a key regulator of the hypothalamic–pituitary–adrenal axis. However, prior work has been exclusively cross-sectional, greatly constraining our understanding of stress-related epigenetic processes over time. In the current study, we examined the effect of maltreatment and other adversity on change in NR3C1 methylation among at-risk preschoolers to begin to characterize within-child epigenetic changes during this sensitive developmental period. Participants were 260 preschoolers (3–5 years-old, 53.8% female), including 51.5% with moderate-severe maltreatment in the past six months. Child protection records, semi-structured interviews, and parent reports were used to assess child stress exposure. Methylation of exons 1D and 1F of NR3C1 via saliva DNA were measured at two time points approximately 6 months apart. Results indicate that maltreated children evidence higher baseline levels of NR3C1 methylation, significant decreases in methylation over time, and then at follow-up, lower levels of methylation, relative to non-maltreated preschoolers. Findings from the current study highlight the complex nature of stress related epigenetic processes during early development.

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Section: Discussionmentioning

confidence: 99%

“…Although there is prior evidence that NR3C1 promoter DNAm is associated with gene expression (Turecki & Meaney, 2016), future longitudinal epigenetics research will benefit from assessing whether the DNAm changes observed alter gene expression (Jones et al, in press). …”

Section: Discussionmentioning

confidence: 99%

Dynamic stress-related epigenetic regulation of the glucocorticoid receptor gene promoter during early development: The role of child maltreatment

et al. 2017

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“…Below, 3 key areas are discussed that can help clarify the role of DNAm in the link between adversity and mental health. We note that other areas not covered here are also important, such as genetic influence, cellular heterogeneity, temporal variability, replication and functional characterization of DNAm [2, 11]. …”

Section: Discussionmentioning

confidence: 99%

“…In recent years, genome-wide DNAm studies have become more popular, due to their increased affordability and data content [11]. The study of Cecil et al [11] reviewed above may be an exemplar, as the top loci formed a network that was plausibly linked with neurodevelopmental risk for substance use.…”

Section: Discussionmentioning

confidence: 99%

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Epigenetics, Early Adversity and Child and Adolescent Mental Health

Barker¹

2018

Psychopathology

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Epigenetic modification, such as DNA methylation (DNAm), is a mechanism that can help explain how early adversities can engender long-term vulnerability for mental health problems. At present, there is preliminary evidence to support the possibility of epigenetic mediation: environmental factors are reported to influence offspring DNAm, which in turn associate with child and adolescent psychopathology. However, all analyses have been correlational in nature and, as these studies have focussed on children and adolescents, DNAm has been based on peripheral tissue (cord blood, whole blood, buccal cells). Therefore, the extent to which DNAm could represent a causal mechanism (e.g., a surrogate of central nervous system function) or a biomarker (i.e., an indicator of the pathological process leading to disease) is unclear. This short report has 2 main components. First, 2 studies are summarized, one a candidate gene study and the other an epigenome-wide association study in which DNAm was reported to (partially) mediate the link between adversity and child development. Second, there is a discussion of (1) the “tissue issue,” (2) maximizing the interpretability of candidate gene and epigenome-wide approaches, and (3) the need for examining DNAm as a potential biomarker for mental health. It is argued that advances within these 3 areas will make clearer the role of DNAm in the link between adversity and child and adolescent mental health.

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Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection

et al. 2022

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ImportanceVery preterm neonates (24-32 weeks’ gestation) remain at a higher risk of morbidity and neurodevelopmental adversity throughout their lifespan. Because the extent of prematurity alone does not fully explain the risk of adverse neonatal brain growth or neurodevelopmental outcomes, there is a need for neonatal biomarkers to help estimate these risks in this population.ObjectivesTo characterize the pediatric buccal epigenetic (PedBE) clock—a recently developed tool to measure biological aging—among very preterm neonates and to assess its association with the extent of prematurity, neonatal comorbidities, neonatal brain growth, and neurodevelopmental outcomes at 18 months of age.Design, Setting, and ParticipantsThis prospective cohort study was conducted in 2 neonatal intensive care units of 2 hospitals in Toronto, Ontario, Canada. A total of 35 very preterm neonates (24-32 weeks’ gestation) were recruited in 2017 and 2018, and neuroimaging was performed and buccal swab samples were acquired at 2 time points: the first in early life (median postmenstrual age, 32.9 weeks [IQR, 32.0-35.0 weeks]) and the second at term-equivalent age (TEA) at a median postmenstrual age of 43.0 weeks (IQR, 41.0-46.0 weeks). Follow-ups for neurodevelopmental assessments were completed in 2019 and 2020. All neonates in this cohort had at least 1 infection because they were originally enrolled to assess the association of neonatal infection with neurodevelopment. Neonates with congenital malformations, genetic syndromes, or congenital TORCH (toxoplasmosis, rubella, cytomegalovirus, herpes and other agents) infection were excluded.ExposuresThe extent of prematurity was measured by gestational age at birth and PedBE age difference. PedBE age was computed using DNA methylation obtained from 94 age-informative CpG (cytosine-phosphate-guanosine) sites. PedBE age difference (weeks) was calculated by subtracting PedBE age at each time point from the corresponding postmenstrual age.Main Outcomes and MeasuresTotal cerebral volumes and cerebral growth during the neonatal intensive care unit period were obtained from magnetic resonance imaging scans at 2 time points: approximately the first 2 weeks of life and at TEA. Bayley Scales of Infant and Toddler Development, Third Edition, were used to assess neurodevelopmental outcomes at 18 months.ResultsAmong 35 very preterm neonates (21 boys [60.0%]; median gestational age, 27.0 weeks [IQR, 25.9-29.9 weeks]; 23 [65.7%] born extremely preterm [&lt;28 weeks’ gestation]), extremely preterm neonates had an accelerated PedBE age compared with neonates born at a later gestational age (β = 9.0; 95% CI, 2.7-15.3; P = .01). An accelerated PedBE age was also associated with smaller cerebral volumes (β = –5356.8; 95% CI, −6899.3 to −2961.7; P = .01) and slower cerebral growth (β = –2651.5; 95% CI, −5301.2 to −1164.1; P = .04); these associations remained significant after adjusting for clinical neonatal factors. These findings were significant at TEA but not earlier in life. Similarly, an accelerated PedBE age at TEA was associated with lower cognitive (β = –0.4; 95% CI, −0.8 to −0.03; P = .04) and language (β = –0.6; 95% CI, −1.1 to −0.06; P = .02) scores at 18 months.Conclusions and RelevanceThis cohort study of very preterm neonates suggests that biological aging may be associated with impaired brain growth and neurodevelopmental outcomes. The associations between epigenetic aging and adverse neonatal brain health warrant further attention.

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Principles and Challenges of Applying Epigenetic Epidemiology to Psychology

Cited by 72 publications

References 146 publications

Dynamic stress-related epigenetic regulation of the glucocorticoid receptor gene promoter during early development: The role of child maltreatment

Dynamic stress-related epigenetic regulation of the glucocorticoid receptor gene promoter during early development: The role of child maltreatment

Epigenetics, Early Adversity and Child and Adolescent Mental Health

Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection

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