Combined polygenic risk scores of different psychiatric traits predict general and specific psychopathology in childhood / Alexander NEUMANN in Journal of Child Psychology and Psychiatry, 63-6 (June 2022)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 63-6 (June 2022) . - p.636-645 Titre : Combined polygenic risk scores of different psychiatric traits predict general and specific psychopathology in childhood Type de document : Texte imprimé et/ou numérique Auteurs : Alexander NEUMANN, Auteur ; Alexia JOLICOEUR-MARTINEAU, Auteur ; Eszter SZEKELY, Auteur ; Hannah M. SALLIS, Auteur ; Kieran O'DONNEL, Auteur ; Celia M. T. GREENWOOD, Auteur ; Robert LEVITAN, Auteur ; Michael J. MEANEY, Auteur ; Ashley WAZANA, Auteur ; Jonathan P. EVANS, Auteur ; Henning TIEMEIER, Auteur Article en page(s) : p.636-645 Langues : Anglais (eng) Mots-clés : Genetics  comorbidity  externalizing disorder  internalizing disorder  meta-analysis  molecular Index. décimale : PER Périodiques Résumé : BACKGROUND: Polygenic risk scores (PRSs) operationalize genetic propensity toward a particular mental disorder and hold promise as early predictors of psychopathology, but before a PRS can be used clinically, explanatory power must be increased and the specificity for a psychiatric domain established. To enable early detection, it is crucial to study these psychometric properties in childhood. We examined whether PRSs associate more with general or with specific psychopathology in school-aged children. Additionally, we tested whether psychiatric PRSs can be combined into a multi-PRS score for improved performance. METHODS: We computed 16 PRSs based on GWASs of psychiatric phenotypes, but also neuroticism and cognitive ability, in mostly adult populations. Study participants were 9,247 school-aged children from three population-based cohorts of the DREAM-BIG consortium: ALSPAC (UK), The Generation R Study (Netherlands), and MAVAN (Canada). We associated each PRS with general and specific psychopathology factors, derived from a bifactor model based on self-report and parental, teacher, and observer reports. After fitting each PRS in separate models, we also tested a multi-PRS model, in which all PRSs are entered simultaneously as predictors of the general psychopathology factor. RESULTS: Seven PRSs were associated with the general psychopathology factor after multiple testing adjustment, two with specific externalizing and five with specific internalizing psychopathology. PRSs predicted general psychopathology independently of each other, with the exception of depression and depressive symptom PRSs. Most PRSs associated with a specific psychopathology domain, were also associated with general child psychopathology. CONCLUSIONS: The results suggest that PRSs based on current GWASs of psychiatric phenotypes tend to be associated with general psychopathology, or both general and specific psychiatric domains, but not with one specific psychopathology domain only. Furthermore, PRSs can be combined to improve predictive ability. PRS users should therefore be conscious of nonspecificity and consider using multiple PRSs simultaneously, when predicting psychiatric disorders. En ligne : http://dx.doi.org/10.1111/jcpp.13501 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=475 [article] Combined polygenic risk scores of different psychiatric traits predict general and specific psychopathology in childhood [Texte imprimé et/ou numérique] / Alexander NEUMANN, Auteur ; Alexia JOLICOEUR-MARTINEAU, Auteur ; Eszter SZEKELY, Auteur ; Hannah M. SALLIS, Auteur ; Kieran O'DONNEL, Auteur ; Celia M. T. GREENWOOD, Auteur ; Robert LEVITAN, Auteur ; Michael J. MEANEY, Auteur ; Ashley WAZANA, Auteur ; Jonathan P. EVANS, Auteur ; Henning TIEMEIER, Auteur . - p.636-645. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 63-6 (June 2022) . - p.636-645 Mots-clés : Genetics  comorbidity  externalizing disorder  internalizing disorder  meta-analysis  molecular Index. décimale : PER Périodiques Résumé : BACKGROUND: Polygenic risk scores (PRSs) operationalize genetic propensity toward a particular mental disorder and hold promise as early predictors of psychopathology, but before a PRS can be used clinically, explanatory power must be increased and the specificity for a psychiatric domain established. To enable early detection, it is crucial to study these psychometric properties in childhood. We examined whether PRSs associate more with general or with specific psychopathology in school-aged children. Additionally, we tested whether psychiatric PRSs can be combined into a multi-PRS score for improved performance. METHODS: We computed 16 PRSs based on GWASs of psychiatric phenotypes, but also neuroticism and cognitive ability, in mostly adult populations. Study participants were 9,247 school-aged children from three population-based cohorts of the DREAM-BIG consortium: ALSPAC (UK), The Generation R Study (Netherlands), and MAVAN (Canada). We associated each PRS with general and specific psychopathology factors, derived from a bifactor model based on self-report and parental, teacher, and observer reports. After fitting each PRS in separate models, we also tested a multi-PRS model, in which all PRSs are entered simultaneously as predictors of the general psychopathology factor. RESULTS: Seven PRSs were associated with the general psychopathology factor after multiple testing adjustment, two with specific externalizing and five with specific internalizing psychopathology. PRSs predicted general psychopathology independently of each other, with the exception of depression and depressive symptom PRSs. Most PRSs associated with a specific psychopathology domain, were also associated with general child psychopathology. CONCLUSIONS: The results suggest that PRSs based on current GWASs of psychiatric phenotypes tend to be associated with general psychopathology, or both general and specific psychiatric domains, but not with one specific psychopathology domain only. Furthermore, PRSs can be combined to improve predictive ability. PRS users should therefore be conscious of nonspecificity and consider using multiple PRSs simultaneously, when predicting psychiatric disorders. En ligne : http://dx.doi.org/10.1111/jcpp.13501 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=475

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 et/ou numérique 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 et/ou numérique] / 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

Exposure to prenatal infection and the development of internalizing and externalizing problems in children: a longitudinal population-based study / Anna-Sophie ROMMEL ; Alexander NEUMANN ; Mannan LUO ; Manon HILLEGERS ; Lotje DE WITTE ; Veerle BERGINK ; Charlotte A. M. CECIL in Journal of Child Psychology and Psychiatry, 65-7 (July 2024)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 65-7 (July 2024) . - p.874-886 Titre : Exposure to prenatal infection and the development of internalizing and externalizing problems in children: a longitudinal population-based study Type de document : Texte imprimé et/ou numérique Auteurs : Anna-Sophie ROMMEL, Auteur ; Alexander NEUMANN, Auteur ; Mannan LUO, Auteur ; Manon HILLEGERS, Auteur ; Lotje DE WITTE, Auteur ; Veerle BERGINK, Auteur ; Charlotte A. M. CECIL, Auteur Article en page(s) : p.874-886 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background A large body of work has reported a link between prenatal exposure to infection and increased psychiatric risk in offspring. However, studies to date have focused primarily on exposure to severe prenatal infections and/or individual psychiatric diagnoses in clinical samples, typically measured at single time points, and without accounting for important genetic and environmental confounders. In this study, we investigated whether exposure to common infections during pregnancy is prospectively associated with repeatedly assessed child psychiatric symptoms in a large population-based study. Methods Our study was embedded in a prospective pregnancy cohort (Generation R; n = 3,598 mother-child dyads). We constructed a comprehensive prenatal infection score comprising common infections for each trimester of pregnancy. Child total, internalizing, and externalizing problems were assessed repeatedly using the parent-rated Child Behavioral Checklist (average age: 1.5, 3, 6, 10, and 14?years). Linear mixed-effects models were run adjusting for a range of confounders, including child polygenic scores for psychopathology, maternal chronic illness, birth complications, and infections during childhood. We also investigated trimester-specific effects and child sex as a potential moderator. Results Prenatal exposure to infections was associated with higher child total, internalizing, and externalizing problems, showing temporally persistent effects, even after adjusting for important genetic and environmental confounders. We found no evidence that prenatal infections were associated with changes in child psychiatric symptoms over time. Moreover, in our trimester-specific analysis, we did not find evidence of significant timing effects of prenatal infection on child psychiatric symptoms. No interactions with child sex were identified. Conclusions Our research adds to evidence that common prenatal infections may be a risk factor for psychiatric symptoms in children. We also extend previous findings by showing that these associations are present early on, and that rather than changing over time, they persist into adolescence. However, unmeasured confounding may still explain in part these associations. In the future, employing more advanced causal inference designs will be crucial to establishing the degree to which these effects are causal. En ligne : https://doi.org/10.1111/jcpp.13923 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=532 [article] Exposure to prenatal infection and the development of internalizing and externalizing problems in children: a longitudinal population-based study [Texte imprimé et/ou numérique] / Anna-Sophie ROMMEL, Auteur ; Alexander NEUMANN, Auteur ; Mannan LUO, Auteur ; Manon HILLEGERS, Auteur ; Lotje DE WITTE, Auteur ; Veerle BERGINK, Auteur ; Charlotte A. M. CECIL, Auteur . - p.874-886. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 65-7 (July 2024) . - p.874-886 Index. décimale : PER Périodiques Résumé : Background A large body of work has reported a link between prenatal exposure to infection and increased psychiatric risk in offspring. However, studies to date have focused primarily on exposure to severe prenatal infections and/or individual psychiatric diagnoses in clinical samples, typically measured at single time points, and without accounting for important genetic and environmental confounders. In this study, we investigated whether exposure to common infections during pregnancy is prospectively associated with repeatedly assessed child psychiatric symptoms in a large population-based study. Methods Our study was embedded in a prospective pregnancy cohort (Generation R; n = 3,598 mother-child dyads). We constructed a comprehensive prenatal infection score comprising common infections for each trimester of pregnancy. Child total, internalizing, and externalizing problems were assessed repeatedly using the parent-rated Child Behavioral Checklist (average age: 1.5, 3, 6, 10, and 14?years). Linear mixed-effects models were run adjusting for a range of confounders, including child polygenic scores for psychopathology, maternal chronic illness, birth complications, and infections during childhood. We also investigated trimester-specific effects and child sex as a potential moderator. Results Prenatal exposure to infections was associated with higher child total, internalizing, and externalizing problems, showing temporally persistent effects, even after adjusting for important genetic and environmental confounders. We found no evidence that prenatal infections were associated with changes in child psychiatric symptoms over time. Moreover, in our trimester-specific analysis, we did not find evidence of significant timing effects of prenatal infection on child psychiatric symptoms. No interactions with child sex were identified. Conclusions Our research adds to evidence that common prenatal infections may be a risk factor for psychiatric symptoms in children. We also extend previous findings by showing that these associations are present early on, and that rather than changing over time, they persist into adolescence. However, unmeasured confounding may still explain in part these associations. In the future, employing more advanced causal inference designs will be crucial to establishing the degree to which these effects are causal. En ligne : https://doi.org/10.1111/jcpp.13923 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=532

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