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 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] / 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 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

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 H.J. 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 Auteurs : Anna-Sophie ROMMEL, Auteur ; Alexander NEUMANN, Auteur ; Mannan LUO, Auteur ; Manon H.J. 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] / Anna-Sophie ROMMEL, Auteur ; Alexander NEUMANN, Auteur ; Mannan LUO, Auteur ; Manon H.J. 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

General psychopathology, internalising and externalising in children and functional outcomes in late adolescence / Hannah SALLIS in Journal of Child Psychology and Psychiatry, 60-11 (November 2019)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 60-11 (November 2019) . - p.1183-1190 Titre : General psychopathology, internalising and externalising in children and functional outcomes in late adolescence Type de document : texte imprimé Auteurs : Hannah SALLIS, Auteur ; Eszter SZEKELY, Auteur ; Alexander NEUMANN, Auteur ; Alexia JOLICOEUR-MARTINEAU, Auteur ; Marinus H. VAN IJZENDOORN, Auteur ; Manon H.J. HILLEGERS, Auteur ; Celia M.T. GREENWOOD, Auteur ; Michael J. MEANEY, Auteur ; Meir STEINER, Auteur ; Henning TIEMEIER, Auteur ; Ashley WAZANA, Auteur ; Rebecca M. PEARSON, Auteur ; Jonathan EVANS, Auteur Article en page(s) : p.1183-1190 Langues : Anglais (eng) Mots-clés : Avon Longitudinal Study of Parents and Children  Childhood psychopathology  Generation Rotterdam  Maternal Adversity  Vulnerability and Neurodevelopment  developmental pathways Index. décimale : PER Périodiques Résumé : BACKGROUND: Internalising and externalising problems commonly co-occur in childhood. Yet, few developmental models describing the structure of child psychopathology appropriately account for this comorbidity. We evaluate a model of childhood psychopathology that separates the unique and shared contribution of individual psychological symptoms into specific internalising, externalising and general psychopathology factors and assess how these general and specific factors predict long-term outcomes concerning criminal behaviour, academic achievement and affective symptoms in three independent cohorts. METHODS: Data were drawn from independent birth cohorts (Avon Longitudinal Study of Parents and Children (ALSPAC), N = 11,612; Generation R, N = 7,946; Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN), N = 408). Child psychopathology was assessed between 4 and 8 years using a range of diagnostic and questionnaire-based measures, and multiple informants. First, structural equation models were used to assess the fit of hypothesised models of shared and unique components of psychopathology in all cohorts. Once the model was chosen, linear/logistic regressions were used to investigate whether these factors were associated with important outcomes such as criminal behaviour, academic achievement and well-being from late adolescence/early adulthood. RESULTS: The model that included specific factors for internalising/externalising and a general psychopathology factor capturing variance shared between symptoms regardless of their classification fits well for all of the cohorts. As hypothesised, general psychopathology factor scores were predictive of all outcomes of later functioning, while specific internalising factor scores predicted later internalising outcomes. Specific externalising factor scores, capturing variance not shared by any other psychological symptoms, were not predictive of later outcomes. CONCLUSIONS: Early symptoms of psychopathology carry information that is syndrome-specific as well as indicative of general vulnerability and the informant reporting on the child. The 'general psychopathology factor' might be more relevant for long-term outcomes than specific symptoms. These findings emphasise the importance of considering the co-occurrence of common internalising and externalising problems in childhood when considering long-term impact. En ligne : http://dx.doi.org/10.1111/jcpp.13067 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408 [article] General psychopathology, internalising and externalising in children and functional outcomes in late adolescence [texte imprimé] / Hannah SALLIS, Auteur ; Eszter SZEKELY, Auteur ; Alexander NEUMANN, Auteur ; Alexia JOLICOEUR-MARTINEAU, Auteur ; Marinus H. VAN IJZENDOORN, Auteur ; Manon H.J. HILLEGERS, Auteur ; Celia M.T. GREENWOOD, Auteur ; Michael J. MEANEY, Auteur ; Meir STEINER, Auteur ; Henning TIEMEIER, Auteur ; Ashley WAZANA, Auteur ; Rebecca M. PEARSON, Auteur ; Jonathan EVANS, Auteur . - p.1183-1190. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 60-11 (November 2019) . - p.1183-1190 Mots-clés : Avon Longitudinal Study of Parents and Children  Childhood psychopathology  Generation Rotterdam  Maternal Adversity  Vulnerability and Neurodevelopment  developmental pathways Index. décimale : PER Périodiques Résumé : BACKGROUND: Internalising and externalising problems commonly co-occur in childhood. Yet, few developmental models describing the structure of child psychopathology appropriately account for this comorbidity. We evaluate a model of childhood psychopathology that separates the unique and shared contribution of individual psychological symptoms into specific internalising, externalising and general psychopathology factors and assess how these general and specific factors predict long-term outcomes concerning criminal behaviour, academic achievement and affective symptoms in three independent cohorts. METHODS: Data were drawn from independent birth cohorts (Avon Longitudinal Study of Parents and Children (ALSPAC), N = 11,612; Generation R, N = 7,946; Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN), N = 408). Child psychopathology was assessed between 4 and 8 years using a range of diagnostic and questionnaire-based measures, and multiple informants. First, structural equation models were used to assess the fit of hypothesised models of shared and unique components of psychopathology in all cohorts. Once the model was chosen, linear/logistic regressions were used to investigate whether these factors were associated with important outcomes such as criminal behaviour, academic achievement and well-being from late adolescence/early adulthood. RESULTS: The model that included specific factors for internalising/externalising and a general psychopathology factor capturing variance shared between symptoms regardless of their classification fits well for all of the cohorts. As hypothesised, general psychopathology factor scores were predictive of all outcomes of later functioning, while specific internalising factor scores predicted later internalising outcomes. Specific externalising factor scores, capturing variance not shared by any other psychological symptoms, were not predictive of later outcomes. CONCLUSIONS: Early symptoms of psychopathology carry information that is syndrome-specific as well as indicative of general vulnerability and the informant reporting on the child. The 'general psychopathology factor' might be more relevant for long-term outcomes than specific symptoms. These findings emphasise the importance of considering the co-occurrence of common internalising and externalising problems in childhood when considering long-term impact. En ligne : http://dx.doi.org/10.1111/jcpp.13067 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408

---

1 (1 - 4 / 4) Par page : 25 50 100 200