Childhood internalising symptoms at ages 3 and 6: a meta-analysis of epigenome-wide associations from cord and peripheral blood / Laura SCHELLHAS in Journal of Child Psychology and Psychiatry, 67-11 (November 2026)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 67-11 (November 2026) . - p.1868-1882 Titre : Childhood internalising symptoms at ages 3 and 6: a meta-analysis of epigenome-wide associations from cord and peripheral blood Type de document : texte imprimé Auteurs : Laura SCHELLHAS, Auteur ; Mannan LUO, Auteur ; Janine F. FELIX, Auteur ; Christian M. PAGE, Auteur ; Mona BEKKHUS, Auteur ; Marcus R. MUNAFO, Auteur ; Luisa ZUCCOLO, Auteur ; Alexandra HAVDAHL, Auteur ; Charlotte A. M. CECIL, Auteur ; Gemma C. SHARP, Auteur Article en page(s) : p.1868-1882 Langues : Anglais (eng) Mots-clés : PACE consortium  internalising problems  DNA methylation Index. décimale : PER Périodiques Résumé : Background Pre- and postpartum environments and genetic effects influence childhood internalising problems, which increase depression risk. DNA methylation (DNAm) may capture some of these effects. We therefore investigated associations between child blood DNAm and internalising problems. Methods We meta-analysed probe and region-level epigenome-wide association studies using data from 3 European birth cohorts (ALSPAC, MoBa, Generation R; analytic N?=?1,121?3,011) from the Pregnancy And Childhood Epigenetics (PACE) Consortium. DNAm was assessed at birth (cord blood) and age 6?years (peripheral blood). Internalising problems (ages 3 and 6) were reported by mothers using the Child Behaviour Checklist or Strengths and Difficulties Questionnaire. Models were adjusted for age at DNAm assessment, 20 surrogate variables, estimated cell proportions, maternal education, age, smoking and, in secondary analysis, maternal anxiety and depression. Public databases were searched for mental health associations with top CpG sites and regions. Results No significant probe-level associations were found between cord- or peripheral-blood DNAm and internalising problems. In region-level analyses, two differentially methylated regions (DMRs) in cord blood were associated with internalising problems at age 3 (annotated to STK32C, MIR886) and one at age 6 (PFKFB2). At age 6, peripheral-blood analyses identified two DMRs (C10orf26 (WBP1L), FAM125A). Several genes showed prior associations with psychiatric phenotypes, including depression. Conclusions The higher-powered regional-level analyses revealed more associations than probe-level. Among others, we identified a region annotated to STK32C that has previously been linked to adolescent depression. Larger samples and refined phenotyping are needed to clarify the role of DNAm in internalising problems. En ligne : https://doi.org/10.1111/jcpp.70186 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=594 [article] Childhood internalising symptoms at ages 3 and 6: a meta-analysis of epigenome-wide associations from cord and peripheral blood [texte imprimé] / Laura SCHELLHAS, Auteur ; Mannan LUO, Auteur ; Janine F. FELIX, Auteur ; Christian M. PAGE, Auteur ; Mona BEKKHUS, Auteur ; Marcus R. MUNAFO, Auteur ; Luisa ZUCCOLO, Auteur ; Alexandra HAVDAHL, Auteur ; Charlotte A. M. CECIL, Auteur ; Gemma C. SHARP, Auteur . - p.1868-1882. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 67-11 (November 2026) . - p.1868-1882 Mots-clés : PACE consortium  internalising problems  DNA methylation Index. décimale : PER Périodiques Résumé : Background Pre- and postpartum environments and genetic effects influence childhood internalising problems, which increase depression risk. DNA methylation (DNAm) may capture some of these effects. We therefore investigated associations between child blood DNAm and internalising problems. Methods We meta-analysed probe and region-level epigenome-wide association studies using data from 3 European birth cohorts (ALSPAC, MoBa, Generation R; analytic N?=?1,121?3,011) from the Pregnancy And Childhood Epigenetics (PACE) Consortium. DNAm was assessed at birth (cord blood) and age 6?years (peripheral blood). Internalising problems (ages 3 and 6) were reported by mothers using the Child Behaviour Checklist or Strengths and Difficulties Questionnaire. Models were adjusted for age at DNAm assessment, 20 surrogate variables, estimated cell proportions, maternal education, age, smoking and, in secondary analysis, maternal anxiety and depression. Public databases were searched for mental health associations with top CpG sites and regions. Results No significant probe-level associations were found between cord- or peripheral-blood DNAm and internalising problems. In region-level analyses, two differentially methylated regions (DMRs) in cord blood were associated with internalising problems at age 3 (annotated to STK32C, MIR886) and one at age 6 (PFKFB2). At age 6, peripheral-blood analyses identified two DMRs (C10orf26 (WBP1L), FAM125A). Several genes showed prior associations with psychiatric phenotypes, including depression. Conclusions The higher-powered regional-level analyses revealed more associations than probe-level. Among others, we identified a region annotated to STK32C that has previously been linked to adolescent depression. Larger samples and refined phenotyping are needed to clarify the role of DNAm in internalising problems. En ligne : https://doi.org/10.1111/jcpp.70186 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=594

Disentangling direct and indirect genetic pathways to neurodevelopmental risk: brain structure and behavior in a population-based parent–offspring trio study / Fin J. E. VAN UUM in Journal of Child Psychology and Psychiatry, 67-11 (November 2026)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 67-11 (November 2026) . - p.1831-1843 Titre : Disentangling direct and indirect genetic pathways to neurodevelopmental risk: brain structure and behavior in a population-based parent–offspring trio study Type de document : texte imprimé Auteurs : Fin J. E. VAN UUM, Auteur ; Yllza XERXA, Auteur ; Alexander NEUMANN, Auteur ; Jean-Baptiste PINGAULT, Auteur ; Charlotte A. M. CECIL, Auteur ; Mina SHAHISAVANDI, Auteur ; Koen BOLHUIS, Auteur ; Boglarka KOVACS, Auteur ; Henning TIEMEIER, Auteur ; Ryan L. MUETZEL, Auteur ; Neeltje E. M. VAN HAREN, Auteur Article en page(s) : p.1831-1843 Langues : Anglais (eng) Mots-clés : Neurodevelopmental disorders  polygenic scores  intergenerational transmission  brain structure  ADHD  MDD Index. décimale : PER Périodiques Résumé : Background Neurodevelopmental disorders (NDDs) are highly heritable, yet the pathways linking parental genetic liability to child outcomes remain poorly understood. Traditional designs cannot easily separate genes transmitted to the child from environmental influences shaped by parental genotypes. Methods In 3,270 families from the Generation R Study, we applied a mother?father?offspring trio design to disentangle direct genetic effects from indirect parental influences (?genetic nurture?). Polygenic scores (PGSs) included a transdiagnostic neurodevelopmental score (NDV) and disorder-specific scores for ADHD, ASD, and major depressive disorder (MDD). Offspring brain structure (cortical surface area, subcortical gray matter, cerebellar volume) at age 9 and behavioral problems at age 14 were assessed. Structural equation modeling was used to test direct, indirect, and brain-mediated genetic pathways. Results Transdiagnostic NDD genetic liability predicted multiple behavioral domains, primarily via direct genetic effects, with similar influence on internalizing and externalizing problems. ADHD PGS effects closely paralleled those of the NDV PGS, whereas ASD and MDD PGSs showed more domain-specific associations. Notably, maternal, but not paternal, MDD genetic liability was indirectly related to behavioral problems across domains, independent of the child's own genetic risk. This maternal pathway was partly reporter-specific but robust for attention problems across both parent and child reports. Global brain measures did not mediate any of the identified genetic pathways. Conclusions Intergenerational NDD risk is predominantly driven by direct genetic transmission. However, maternal depression liability exerts additional influence through environmentally mediated pathways. The absence of brain-mediated effects suggests that the gross neural phenotypes examined here do not capture the mechanisms underlying these pathways. Our findings highlight the importance of maternal influences on child NDD outcomes and underscore the need for longitudinal, multimodal research designs that integrate genetic, caregiving, and fine-grained neural phenotyping data to inform targeted prevention and early intervention strategies for at-risk families. En ligne : https://doi.org/10.1111/jcpp.70184 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=594 [article] Disentangling direct and indirect genetic pathways to neurodevelopmental risk: brain structure and behavior in a population-based parent–offspring trio study [texte imprimé] / Fin J. E. VAN UUM, Auteur ; Yllza XERXA, Auteur ; Alexander NEUMANN, Auteur ; Jean-Baptiste PINGAULT, Auteur ; Charlotte A. M. CECIL, Auteur ; Mina SHAHISAVANDI, Auteur ; Koen BOLHUIS, Auteur ; Boglarka KOVACS, Auteur ; Henning TIEMEIER, Auteur ; Ryan L. MUETZEL, Auteur ; Neeltje E. M. VAN HAREN, Auteur . - p.1831-1843. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 67-11 (November 2026) . - p.1831-1843 Mots-clés : Neurodevelopmental disorders  polygenic scores  intergenerational transmission  brain structure  ADHD  MDD Index. décimale : PER Périodiques Résumé : Background Neurodevelopmental disorders (NDDs) are highly heritable, yet the pathways linking parental genetic liability to child outcomes remain poorly understood. Traditional designs cannot easily separate genes transmitted to the child from environmental influences shaped by parental genotypes. Methods In 3,270 families from the Generation R Study, we applied a mother?father?offspring trio design to disentangle direct genetic effects from indirect parental influences (?genetic nurture?). Polygenic scores (PGSs) included a transdiagnostic neurodevelopmental score (NDV) and disorder-specific scores for ADHD, ASD, and major depressive disorder (MDD). Offspring brain structure (cortical surface area, subcortical gray matter, cerebellar volume) at age 9 and behavioral problems at age 14 were assessed. Structural equation modeling was used to test direct, indirect, and brain-mediated genetic pathways. Results Transdiagnostic NDD genetic liability predicted multiple behavioral domains, primarily via direct genetic effects, with similar influence on internalizing and externalizing problems. ADHD PGS effects closely paralleled those of the NDV PGS, whereas ASD and MDD PGSs showed more domain-specific associations. Notably, maternal, but not paternal, MDD genetic liability was indirectly related to behavioral problems across domains, independent of the child's own genetic risk. This maternal pathway was partly reporter-specific but robust for attention problems across both parent and child reports. Global brain measures did not mediate any of the identified genetic pathways. Conclusions Intergenerational NDD risk is predominantly driven by direct genetic transmission. However, maternal depression liability exerts additional influence through environmentally mediated pathways. The absence of brain-mediated effects suggests that the gross neural phenotypes examined here do not capture the mechanisms underlying these pathways. Our findings highlight the importance of maternal influences on child NDD outcomes and underscore the need for longitudinal, multimodal research designs that integrate genetic, caregiving, and fine-grained neural phenotyping data to inform targeted prevention and early intervention strategies for at-risk families. En ligne : https://doi.org/10.1111/jcpp.70184 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=594

Longitudinal co-development of mental and cardio-metabolic health from childhood to young adulthood / Serena DEFINA in Journal of Child Psychology and Psychiatry, 67-3 (March 2026)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 67-3 (March 2026) . - p.413-424 Titre : Longitudinal co-development of mental and cardio-metabolic health from childhood to young adulthood Type de document : texte imprimé Auteurs : Serena DEFINA, Auteur ; Charlotte A. M. CECIL, Auteur ; Janine F. FELIX, Auteur ; Esther WALTON, Auteur ; Henning TIEMEIER, Auteur Article en page(s) : p.413-424 Langues : Anglais (eng) Mots-clés : Depressive symptoms  cardio-metabolic risk  comorbidity  longitudinal  ALSPAC Index. décimale : PER Périodiques Résumé : Background Depressive symptoms and cardio-metabolic risk factors often co-occur. However, our understanding of the potential mechanisms and temporal dynamics underlying their co-development remains elusive. Methods This population-based cohort study examined bidirectional longitudinal associations between depressive symptoms and cardio-metabolic risk factors from age 10 to 25?years, using prospective data from the ALSPAC Study. Participants with at least one (of six) follow-up measurement for each outcome were included in the analyses. We measured depressive symptoms through self- as well as parent-reports, and assessed several cardio-metabolic risk factors (including adiposity measures, lipid profiles, and inflammation). Results Among our 7,970 (47% male, 96% White) participants, we found bidirectional, within-person associations between self-reported depressive symptoms and adiposity (i.e., fat/lean mass index, but not body mass index), across the study period. Adiposity was more stable over time (? [range]?=?0.75 [0.54; 0.84]), compared to depressive symptoms (0.26 [0.12; 0.38]), and it had a stronger prospective (i.e., cross-lagged) association with future depressive symptoms (0.07 [0.03, 0.13]) compared to that between depressive symptoms and future adiposity (0.04 [0.03, 0.06]). The magnitude of these associations reached its peak between 14 and 16?years. We did not find evidence of cross-lagged associations in either direction between depressive symptoms and waist circumference, insulin, triglycerides, LDL cholesterol, or C-reactive protein. Conclusions These findings suggest a bidirectional relationship between depressive symptoms and cardio-metabolic risk factors, particularly adiposity (i.e., fat/lean mass). Adiposity showed a stronger prospective association with future depressive symptoms than vice versa; however, their relationship revealed more reciprocal than previously thought. En ligne : https://doi.org/10.1111/jcpp.70065 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=580 [article] Longitudinal co-development of mental and cardio-metabolic health from childhood to young adulthood [texte imprimé] / Serena DEFINA, Auteur ; Charlotte A. M. CECIL, Auteur ; Janine F. FELIX, Auteur ; Esther WALTON, Auteur ; Henning TIEMEIER, Auteur . - p.413-424. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 67-3 (March 2026) . - p.413-424 Mots-clés : Depressive symptoms  cardio-metabolic risk  comorbidity  longitudinal  ALSPAC Index. décimale : PER Périodiques Résumé : Background Depressive symptoms and cardio-metabolic risk factors often co-occur. However, our understanding of the potential mechanisms and temporal dynamics underlying their co-development remains elusive. Methods This population-based cohort study examined bidirectional longitudinal associations between depressive symptoms and cardio-metabolic risk factors from age 10 to 25?years, using prospective data from the ALSPAC Study. Participants with at least one (of six) follow-up measurement for each outcome were included in the analyses. We measured depressive symptoms through self- as well as parent-reports, and assessed several cardio-metabolic risk factors (including adiposity measures, lipid profiles, and inflammation). Results Among our 7,970 (47% male, 96% White) participants, we found bidirectional, within-person associations between self-reported depressive symptoms and adiposity (i.e., fat/lean mass index, but not body mass index), across the study period. Adiposity was more stable over time (? [range]?=?0.75 [0.54; 0.84]), compared to depressive symptoms (0.26 [0.12; 0.38]), and it had a stronger prospective (i.e., cross-lagged) association with future depressive symptoms (0.07 [0.03, 0.13]) compared to that between depressive symptoms and future adiposity (0.04 [0.03, 0.06]). The magnitude of these associations reached its peak between 14 and 16?years. We did not find evidence of cross-lagged associations in either direction between depressive symptoms and waist circumference, insulin, triglycerides, LDL cholesterol, or C-reactive protein. Conclusions These findings suggest a bidirectional relationship between depressive symptoms and cardio-metabolic risk factors, particularly adiposity (i.e., fat/lean mass). Adiposity showed a stronger prospective association with future depressive symptoms than vice versa; however, their relationship revealed more reciprocal than previously thought. En ligne : https://doi.org/10.1111/jcpp.70065 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=580

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