Annual Research Review: DNA methylation as a mediator in the association between risk exposure and child and adolescent psychopathology / Edward D. BARKER in Journal of Child Psychology and Psychiatry, 59-4 (April 2018)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 59-4 (April 2018) . - p.303-322 Titre : Annual Research Review: DNA methylation as a mediator in the association between risk exposure and child and adolescent psychopathology Type de document : texte imprimé Auteurs : Edward D. BARKER, Auteur ; Esther WALTON, Auteur ; Charlotte A.M. CECIL, Auteur Article en page(s) : p.303-322 Langues : Anglais (eng) Mots-clés : DNA methylation  adolescence  childhood  developmental psychopathology  environmental risk  epigenetics  externalising problems  internalising problems Index. décimale : PER Périodiques Résumé : BACKGROUND: DNA methylation (DNAm) is a potential mechanism for propagating the effects of environmental exposures on child and adolescent mental health. In recent years, this field has experienced steady growth. METHODS: We provide a strategic review of the current child and adolescent literature to evaluate evidence for a mediating role of DNAm in the link between environmental risks and psychopathological outcomes, with a focus on internalising and externalising difficulties. RESULTS: Based on the studies presented, we conclude that there is preliminary evidence to support that (a) environmental factors, such as diet, neurotoxic exposures and stress, influence offspring DNAm, and that (b) variability in DNAm, in turn, is associated with child and adolescent psychopathology. Overall, very few studies have examined DNAm in relation to both exposures and outcomes, and almost all analyses have been correlational in nature. CONCLUSIONS: DNAm holds potential as a biomarker indexing both environmental risk exposure and vulnerability for child psychopathology. However, the extent to which it may represent a causal mediator is not clear. In future, collection of prospective risk exposure, DNAm and outcomes - as well as functional characterisation of epigenetic findings - will assist in determining the role of DNAm in the link between risk exposure and psychopathology. En ligne : http://dx.doi.org/10.1111/jcpp.12782 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=353 [article] Annual Research Review: DNA methylation as a mediator in the association between risk exposure and child and adolescent psychopathology [texte imprimé] / Edward D. BARKER, Auteur ; Esther WALTON, Auteur ; Charlotte A.M. CECIL, Auteur . - p.303-322. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 59-4 (April 2018) . - p.303-322 Mots-clés : DNA methylation  adolescence  childhood  developmental psychopathology  environmental risk  epigenetics  externalising problems  internalising problems Index. décimale : PER Périodiques Résumé : BACKGROUND: DNA methylation (DNAm) is a potential mechanism for propagating the effects of environmental exposures on child and adolescent mental health. In recent years, this field has experienced steady growth. METHODS: We provide a strategic review of the current child and adolescent literature to evaluate evidence for a mediating role of DNAm in the link between environmental risks and psychopathological outcomes, with a focus on internalising and externalising difficulties. RESULTS: Based on the studies presented, we conclude that there is preliminary evidence to support that (a) environmental factors, such as diet, neurotoxic exposures and stress, influence offspring DNAm, and that (b) variability in DNAm, in turn, is associated with child and adolescent psychopathology. Overall, very few studies have examined DNAm in relation to both exposures and outcomes, and almost all analyses have been correlational in nature. CONCLUSIONS: DNAm holds potential as a biomarker indexing both environmental risk exposure and vulnerability for child psychopathology. However, the extent to which it may represent a causal mediator is not clear. In future, collection of prospective risk exposure, DNAm and outcomes - as well as functional characterisation of epigenetic findings - will assist in determining the role of DNAm in the link between risk exposure and psychopathology. En ligne : http://dx.doi.org/10.1111/jcpp.12782 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=353

DNA methylation at birth and lateral ventricular volume in childhood: a neuroimaging epigenetics study / Esther WALTON ; Alexander NEUMANN ; Chris H.L. THIO ; Janine F. FELIX ; Marinus H. VAN IJZENDOORN ; Irene PAPPA ; Charlotte A.M. CECIL in Journal of Child Psychology and Psychiatry, 65-1 (January 2024)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 65-1 (January 2024) . - p.77-90 Titre : DNA methylation at birth and lateral ventricular volume in childhood: a neuroimaging epigenetics study Type de document : texte imprimé Auteurs : Esther WALTON, Auteur ; Alexander NEUMANN, Auteur ; Chris H.L. THIO, Auteur ; Janine F. FELIX, Auteur ; Marinus H. VAN IJZENDOORN, Auteur ; Irene PAPPA, Auteur ; Charlotte A.M. CECIL, Auteur Article en page(s) : p.77-90 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background Lateral 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. Methods In 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). Results At 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. Conclusions This 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. En ligne : https://doi.org/10.1111/jcpp.13866 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518 [article] DNA methylation at birth and lateral ventricular volume in childhood: a neuroimaging epigenetics study [texte imprimé] / Esther WALTON, Auteur ; Alexander NEUMANN, Auteur ; Chris H.L. THIO, Auteur ; Janine F. FELIX, Auteur ; Marinus H. VAN IJZENDOORN, Auteur ; Irene PAPPA, Auteur ; Charlotte A.M. CECIL, Auteur . - p.77-90. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 65-1 (January 2024) . - p.77-90 Index. décimale : PER Périodiques Résumé : Background Lateral 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. Methods In 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). Results At 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. Conclusions This 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. En ligne : https://doi.org/10.1111/jcpp.13866 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518

Inflammation-related epigenetic risk and child and adolescent mental health: A prospective study from pregnancy to middle adolescence / Edward D. BARKER in Development and Psychopathology, 30-3 (August 2018)  

Public ISBD [article]  inDevelopment and Psychopathology > 30-3 (August 2018) . - p.1145-1156 Titre : Inflammation-related epigenetic risk and child and adolescent mental health: A prospective study from pregnancy to middle adolescence Type de document : texte imprimé Auteurs : Edward D. BARKER, Auteur ; Charlotte A.M. CECIL, Auteur ; Esther WALTON, Auteur ; Lotte C. HOUTEPEN, Auteur ; Thomas G. O'CONNOR, Auteur ; Andrea DANESE, Auteur ; Sara R. JAFFEE, Auteur ; Sarah K.G. JENSEN, Auteur ; Carmine M. PARIANTE, Auteur ; Wendy MCARDLE, Auteur ; Tom R. GAUNT, Auteur ; Caroline L. RELTON, Auteur ; S. Wendy ROBERTS, Auteur Article en page(s) : p.1145-1156 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : In 785 mother-child (50% male) pairs from a longitudinal epidemiological birth cohort, we investigated associations between inflammation-related epigenetic polygenic risk scores (i-ePGS), environmental exposures, cognitive function, and child and adolescent internalizing and externalizing problems. We examined prenatal and postnatal effects. For externalizing problems, one prenatal effect was found: i-ePGS at birth associated with higher externalizing problems (ages 7-15) indirectly through lower cognitive function (age 7). For internalizing problems, we identified two effects. For a prenatal effect, i-ePGS at birth associated with higher internalizing symptoms via continuity in i-ePGS at age 7. For a postnatal effect, higher postnatal adversity exposure (birth through age 7) associated with higher internalizing problems (ages 7-15) via higher i-ePGS (age 7). Hence, externalizing problems were related mainly to prenatal effects involving lower cognitive function, whereas internalizing problems appeared related to both prenatal and postnatal effects. The present study supports a link between i-ePGS and child and adolescent mental health. En ligne : http://dx.doi.org/10.1017/s0954579418000330 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=367 [article] Inflammation-related epigenetic risk and child and adolescent mental health: A prospective study from pregnancy to middle adolescence [texte imprimé] / Edward D. BARKER, Auteur ; Charlotte A.M. CECIL, Auteur ; Esther WALTON, Auteur ; Lotte C. HOUTEPEN, Auteur ; Thomas G. O'CONNOR, Auteur ; Andrea DANESE, Auteur ; Sara R. JAFFEE, Auteur ; Sarah K.G. JENSEN, Auteur ; Carmine M. PARIANTE, Auteur ; Wendy MCARDLE, Auteur ; Tom R. GAUNT, Auteur ; Caroline L. RELTON, Auteur ; S. Wendy ROBERTS, Auteur . - p.1145-1156. Langues : Anglais (eng) in Development and Psychopathology > 30-3 (August 2018) . - p.1145-1156 Index. décimale : PER Périodiques Résumé : In 785 mother-child (50% male) pairs from a longitudinal epidemiological birth cohort, we investigated associations between inflammation-related epigenetic polygenic risk scores (i-ePGS), environmental exposures, cognitive function, and child and adolescent internalizing and externalizing problems. We examined prenatal and postnatal effects. For externalizing problems, one prenatal effect was found: i-ePGS at birth associated with higher externalizing problems (ages 7-15) indirectly through lower cognitive function (age 7). For internalizing problems, we identified two effects. For a prenatal effect, i-ePGS at birth associated with higher internalizing symptoms via continuity in i-ePGS at age 7. For a postnatal effect, higher postnatal adversity exposure (birth through age 7) associated with higher internalizing problems (ages 7-15) via higher i-ePGS (age 7). Hence, externalizing problems were related mainly to prenatal effects involving lower cognitive function, whereas internalizing problems appeared related to both prenatal and postnatal effects. The present study supports a link between i-ePGS and child and adolescent mental health. En ligne : http://dx.doi.org/10.1017/s0954579418000330 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=367

Longitudinal epigenetic predictors of amygdala:hippocampus volume ratio / Esther WALTON in Journal of Child Psychology and Psychiatry, 58-12 (December 2017)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 58-12 (December 2017) . - p.1341-1350 Titre : Longitudinal epigenetic predictors of amygdala:hippocampus volume ratio Type de document : texte imprimé Auteurs : Esther WALTON, Auteur ; Charlotte A.M. CECIL, Auteur ; Matthew SUDERMAN, Auteur ; Jingyu LIU, Auteur ; Jessica A. TURNER, Auteur ; Vince D. CALHOUN, Auteur ; Stefan EHRLICH, Auteur ; Caroline L. RELTON, Auteur ; Edward D. BARKER, Auteur Article en page(s) : p.1341-1350 Langues : Anglais (eng) Mots-clés : DNA methylation  methylome-wide  amygdala  hippocampus  longitudinal  Avon Longitudinal Study of Parents and Children Index. décimale : PER Périodiques Résumé : Background The ratio between amygdala:hippocampal (AH) volume has been associated with multiple psychiatric problems, including anxiety and aggression. Yet, little is known about its biological underpinnings. Here, we used a methylome-wide approach to test (a) whether DNA methylation in early life (birth, age 7) prospectively associates with total AH volume ratio in early adulthood, and (b) whether significant DNA methylation markers are influenced by prenatal risk factors. Methods Analyses were based on a subsample (n = 109 males) from the Avon Longitudinal Study of Parents and Children, which included measures of prenatal risk, DNA methylation (Infinium Illumina 450k), T1-weighted brain scans and psychopathology in early adulthood (age 18–21). Amygdala and hippocampus measures were derived using Freesurfer 5.3.0. Methylation markers related to AH volume ratio across time were identified using longitudinal multilevel modeling. Results Amygdala:hippocampal volume ratio correlated positively with age 18 psychosis-like symptoms (p = .007). Methylation of a probe in the gene SP6 associated longitudinally with (a) higher AH volume ratio (FDR q-value = .01) and (b) higher stressful life events during pregnancy (p = .046). SP6 is expressed in the hippocampus and amygdala and has been implicated in cognitive decline in Alzheimer's disease. The association between SP6 DNA methylation, AH volume ratio and psychopathology was replicated in an independent dataset of 101 patients with schizophrenia and 111 healthy controls. Conclusions Our findings suggest that epigenetic alterations in genes implicated in neurodevelopment may contribute to a brain-based biomarker of psychopathology. En ligne : http://dx.doi.org/10.1111/jcpp.12740 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=326 [article] Longitudinal epigenetic predictors of amygdala:hippocampus volume ratio [texte imprimé] / Esther WALTON, Auteur ; Charlotte A.M. CECIL, Auteur ; Matthew SUDERMAN, Auteur ; Jingyu LIU, Auteur ; Jessica A. TURNER, Auteur ; Vince D. CALHOUN, Auteur ; Stefan EHRLICH, Auteur ; Caroline L. RELTON, Auteur ; Edward D. BARKER, Auteur . - p.1341-1350. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 58-12 (December 2017) . - p.1341-1350 Mots-clés : DNA methylation  methylome-wide  amygdala  hippocampus  longitudinal  Avon Longitudinal Study of Parents and Children Index. décimale : PER Périodiques Résumé : Background The ratio between amygdala:hippocampal (AH) volume has been associated with multiple psychiatric problems, including anxiety and aggression. Yet, little is known about its biological underpinnings. Here, we used a methylome-wide approach to test (a) whether DNA methylation in early life (birth, age 7) prospectively associates with total AH volume ratio in early adulthood, and (b) whether significant DNA methylation markers are influenced by prenatal risk factors. Methods Analyses were based on a subsample (n = 109 males) from the Avon Longitudinal Study of Parents and Children, which included measures of prenatal risk, DNA methylation (Infinium Illumina 450k), T1-weighted brain scans and psychopathology in early adulthood (age 18–21). Amygdala and hippocampus measures were derived using Freesurfer 5.3.0. Methylation markers related to AH volume ratio across time were identified using longitudinal multilevel modeling. Results Amygdala:hippocampal volume ratio correlated positively with age 18 psychosis-like symptoms (p = .007). Methylation of a probe in the gene SP6 associated longitudinally with (a) higher AH volume ratio (FDR q-value = .01) and (b) higher stressful life events during pregnancy (p = .046). SP6 is expressed in the hippocampus and amygdala and has been implicated in cognitive decline in Alzheimer's disease. The association between SP6 DNA methylation, AH volume ratio and psychopathology was replicated in an independent dataset of 101 patients with schizophrenia and 111 healthy controls. Conclusions Our findings suggest that epigenetic alterations in genes implicated in neurodevelopment may contribute to a brain-based biomarker of psychopathology. En ligne : http://dx.doi.org/10.1111/jcpp.12740 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=326

Neonatal DNA methylation and early-onset conduct problems: A genome-wide, prospective study / Charlotte A.M. CECIL in Development and Psychopathology, 30-2 (May 2018)  

Public ISBD [article]  inDevelopment and Psychopathology > 30-2 (May 2018) . - p.383-397 Titre : Neonatal DNA methylation and early-onset conduct problems: A genome-wide, prospective study Type de document : texte imprimé Auteurs : Charlotte A.M. CECIL, Auteur ; Esther WALTON, Auteur ; Sara R. JAFFEE, Auteur ; Tom O'CONNOR, Auteur ; Barbara MAUGHAN, Auteur ; Caroline L. RELTON, Auteur ; Rebecca G. SMITH, Auteur ; Wendy MCARDLE, Auteur ; Tom R. GAUNT, Auteur ; Isabelle OUELLET-MORIN, Auteur ; Edward D. BARKER, Auteur Article en page(s) : p.383-397 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Early-onset conduct problems (CP) are a key predictor of adult criminality and poor mental health. While previous studies suggest that both genetic and environmental risks play an important role in the development of early-onset CP, little is known about potential biological processes underlying these associations. In this study, we examined prospective associations between DNA methylation (cord blood at birth) and trajectories of CP (4–13 years), using data drawn from the Avon Longitudinal Study of Parents and Children. Methylomic variation at seven loci across the genome (false discovery rate < 0.05) differentiated children who go on to develop early-onset (n = 174) versus low (n = 86) CP, including sites in the vicinity of the monoglyceride lipase (MGLL) gene (involved in endocannabinoid signaling and pain perception). Subthreshold associations in the vicinity of three candidate genes for CP (monoamine oxidase A [MAOA], brain-derived neurotrophic factor [BDNF], and FK506 binding protein 5 [FKBP5]) were also identified. Within the early-onset CP group, methylation levels of the identified sites did not distinguish children who will go on to persist versus desist in CP behavior over time. Overall, we found that several of the identified sites correlated with prenatal exposures, and none were linked to known genetic methylation quantitative trait loci. Findings contribute to a better understanding of epigenetic patterns associated with early-onset CP. En ligne : http://dx.doi.org/10.1017/S095457941700092X Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=358 [article] Neonatal DNA methylation and early-onset conduct problems: A genome-wide, prospective study [texte imprimé] / Charlotte A.M. CECIL, Auteur ; Esther WALTON, Auteur ; Sara R. JAFFEE, Auteur ; Tom O'CONNOR, Auteur ; Barbara MAUGHAN, Auteur ; Caroline L. RELTON, Auteur ; Rebecca G. SMITH, Auteur ; Wendy MCARDLE, Auteur ; Tom R. GAUNT, Auteur ; Isabelle OUELLET-MORIN, Auteur ; Edward D. BARKER, Auteur . - p.383-397. Langues : Anglais (eng) in Development and Psychopathology > 30-2 (May 2018) . - p.383-397 Index. décimale : PER Périodiques Résumé : Early-onset conduct problems (CP) are a key predictor of adult criminality and poor mental health. While previous studies suggest that both genetic and environmental risks play an important role in the development of early-onset CP, little is known about potential biological processes underlying these associations. In this study, we examined prospective associations between DNA methylation (cord blood at birth) and trajectories of CP (4–13 years), using data drawn from the Avon Longitudinal Study of Parents and Children. Methylomic variation at seven loci across the genome (false discovery rate < 0.05) differentiated children who go on to develop early-onset (n = 174) versus low (n = 86) CP, including sites in the vicinity of the monoglyceride lipase (MGLL) gene (involved in endocannabinoid signaling and pain perception). Subthreshold associations in the vicinity of three candidate genes for CP (monoamine oxidase A [MAOA], brain-derived neurotrophic factor [BDNF], and FK506 binding protein 5 [FKBP5]) were also identified. Within the early-onset CP group, methylation levels of the identified sites did not distinguish children who will go on to persist versus desist in CP behavior over time. Overall, we found that several of the identified sites correlated with prenatal exposures, and none were linked to known genetic methylation quantitative trait loci. Findings contribute to a better understanding of epigenetic patterns associated with early-onset CP. En ligne : http://dx.doi.org/10.1017/S095457941700092X Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=358

Prenatal unhealthy diet, insulin-like growth factor 2 gene (IGF2) methylation, and attention deficit hyperactivity disorder symptoms in youth with early-onset conduct problems / Jolien RIJLAARSDAM in Journal of Child Psychology and Psychiatry, 58-1 (January 2017)  

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