Inflammation-related epigenetic risk and child and adolescent mental health: A prospective study from pregnancy to middle adolescence

Barker, Edward D.; Cecil, Charlotte A.M.; Walton, Esther; Houtepen, Lotte C; O’Connor, Thomas G.; Danese, Andrea; Jaffee, Sara R.; Jensen, Sarah; Pariante, Carmine M.; McArdle, Wendy L.; Gaunt, Tom R.; Relton, Caroline L; Roberts, Stephen K.

doi:10.1017/s0954579418000330

Cited by 51 publications

(54 citation statements)

References 85 publications

(115 reference statements)

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“…No associations were found between g f and the genetic score, marking the epigenetic score as having the most powerful association with cognitive ability. Our results are consistent with a recent study identifying a negative association between i-PEGS at birth, and cognitive function in early life (26). This, coupled with our results from GS, whose participant ages span early-adulthood to later-life, suggests inflammation and cognition may be related across the life-course rather than necessarily exclusively in older age.…”

Section: Discussionsupporting

confidence: 93%

“…An inflammation-related poly-epigenetic score (i-PEGS) was derived for each participant as described by Barker et al (26). Briefly, methylation beta values were extracted for the 7 CpG sites shown to have the strongest evidence of a functional association with serum CRP levels.…”

Section: Methodsmentioning

confidence: 99%

“…Ligthart et al identified differential methylation at 58 CpG sites that replicated across both a large European (n = 8,863) and African-American (n = 4,111) cohort. Using 7 CpG sites from this data, an inflammation-related epigenetic risk score was recently created and applied in a developmental framework investigating inflammation and child and adolescent mental health (26).…”

Section: Introductionmentioning

confidence: 99%

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Characterisation of an inflammation-related epigenetic score and its association with cognitive ability

Stevenson

McCartney

Hillary

et al. 2019

Preprint

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Results from large cohort studies investigating the association between inflammation and cognition have been mixed, possibly due to methodological disparities. However, a key issue in research utilising inflammatory biomarkers is their typically phasic responses. C-reactive protein (CRP) is widely used to investigate the association between chronic inflammation and cognition, but its plasma concentrations can markedly deviate in response to acute infection. Recently a large-scale epigenome-wide association study identified DNA methylation correlates of CRP. DNA methylation is thought to be relatively stable in the short term, marking it as a potentially useful signature of exposure. Here, we generate an epigenetic CRP score and investigate its trajectories with age, and associations with cognitive ability, in comparison to serum CRP in two cohorts: a longitudinal study of older adults (the Lothian Birth Cohort 1936, n=889) and a large, cross-sectional cohort (Generation Scotland, n=7,028).We identified differing trajectories of serum CRP across the cohorts, with no homogeneous trends seen with age. Conversely, the epigenetic score was consistently found to increase with age, and to do so more rapidly in males compared to females. Higher levels of serum CRP were found to associate with poorer cognition in Lothian Birth Cohort 1936, but not in Generation Scotland. However, a consistent negative association was identified between cognition and the epigenetic score in both cohorts. Furthermore, the epigenetic score accounted for a greater proportion of variance in cognitive ability.Our results suggest that epigenetic signatures of acute inflammatory markers may provide an enhanced signature of chronic inflammation, allowing for more reliable stratification of individuals, and thus clearer inference of associations with incident health outcomes.

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Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characterisation of an inflammation-related epigenetic score and its association with cognitive ability

Stevenson

McCartney

Hillary

et al. 2019

Preprint

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“…Using the British Avon Longitudinal Study of Parents and Children (ALSPAC) cohort followed from birth, Cecil et al (2014) published results showing that the epigenetic differences we observed during adulthood, with the Montreal study described earlier, may be related to prenatal and perinatal mechanisms. For a subgroup of children, they found that higher maternal psychopathology, criminal behavior, and substance use was associated with higher oxytocin receptor gene methylation at birth, and that this DNA methylation at birth was associated with higher Callous-Unemotional traits at 13 years of age (E. D. Barker et al, 2018).…”

Section: Epigenetic Effectsmentioning

confidence: 99%

Sex differences in the development of physical aggression: An intergenerational perspective and implications for preventive interventions

Tremblay

Côté

2019

Infant Mental Health Journal

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This article reviews the state of knowledge on the development of chronic physical aggression (CPA), with the aim of identifying the most effective prevention strategies. We specifically focus on the early development of physical aggression, on sex differences in the use of physical aggression, and on the transmission of behavior problems from one generation to the other. The body of research on the development of CPA from the past three decades that we review shows increasing evidence that its prevention requires a long‐term biopsychosocial developmental approach which also must include an intergenerational perspective. Recent genetic and epigenetic research has indicated that there are both important genetic and environmental effects on gene expression which start at conception. We conclude that one of the most effective strategies to break the intergenerational transmission of CPA involves giving long‐term support to pregnant women with a history of behavior problems, their spouse, and their offspring.

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“…Recently, a large-scale EWAS of serum CRP in adults (n = 8863 and 4111 of European and African ancestries, respectively) identified DNA methylation correlates of chronic low-grade inflammation [25]. Using 7 CpG sites from this data, an inflammation-related epigenetic risk score was recently created and applied in a developmental framework investigating inflammation and child and adolescent mental health [26].…”

Section: Introductionmentioning

confidence: 99%

Characterisation of an inflammation-related epigenetic score and its association with cognitive ability

et al. 2020

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Background: Chronic systemic inflammation has been associated with incident dementia, but its association with age-related cognitive decline is less clear. The acute responses of many inflammatory biomarkers mean they may provide an unreliable picture of the chronicity of inflammation. Recently, a large-scale epigenome-wide association study identified DNA methylation correlates of C-reactive protein (CRP)-a widely used acute-phase inflammatory biomarker. DNA methylation is thought to be relatively stable in the short term, marking it as a potentially useful signature of exposure. Methods: We utilise a DNA methylation-based score for CRP and investigate its trajectories with age, and associations with cognitive ability in comparison with serum CRP and a genetic CRP score in a longitudinal study of older adults (n = 889) and a large, cross-sectional cohort (n = 7028). Results: We identified no homogeneous trajectories of serum CRP with age across the cohorts, whereas the epigenetic CRP score was consistently found to increase with age (standardised β = 0.07 and 0.01) and to do so more rapidly in males compared to females. Additionally, the epigenetic CRP score had higher test-retest reliability compared to serum CRP, indicating its enhanced temporal stability. Higher serum CRP was not found to be associated with poorer cognitive ability (standardised β = − 0.08 and − 0.05); however, a consistent negative association was identified between cognitive ability and the epigenetic CRP score in both cohorts (standardised β = − 0.15 and − 0.08). Conclusions: An epigenetic proxy of CRP may provide a more reliable signature of chronic inflammation, allowing for more accurate stratification of individuals, and thus clearer inference of associations with incident health outcomes.

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Inflammation-related epigenetic risk and child and adolescent mental health: A prospective study from pregnancy to middle adolescence

Cited by 51 publications

References 85 publications

Characterisation of an inflammation-related epigenetic score and its association with cognitive ability

Characterisation of an inflammation-related epigenetic score and its association with cognitive ability

Sex differences in the development of physical aggression: An intergenerational perspective and implications for preventive interventions

Characterisation of an inflammation-related epigenetic score and its association with cognitive ability

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