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

Distinguishing differential susceptibility, diathesis-stress, and vantage sensitivity: Beyond the single gene and environment model / Alexia JOLICOEUR-MARTINEAU in Development and Psychopathology, 32-1 (February 2020)  

Public ISBD [article]  inDevelopment and Psychopathology > 32-1 (February 2020) . - p.73-83 Titre : Distinguishing differential susceptibility, diathesis-stress, and vantage sensitivity: Beyond the single gene and environment model Type de document : Texte imprimé et/ou numérique Auteurs : Alexia JOLICOEUR-MARTINEAU, Auteur ; Jay BELSKY, Auteur ; Eszter SZEKELY, Auteur ; Keith F. WIDAMAN, Auteur ; Michael PLUESS, Auteur ; Celia M. T. GREENWOOD, Auteur ; Ashley WAZANA, Auteur Article en page(s) : p.73-83 Langues : Anglais (eng) Mots-clés : diathesis-stress  differential-susceptibility  gene-by-environment interaction  regions of significance  vantage sensitivity Index. décimale : PER Périodiques Résumé : Currently, two main approaches exist to distinguish differential susceptibility from diathesis-stress and vantage sensitivity in Genotype x Environment interaction (G x E) research: regions of significance (RoS) and competitive-confirmatory approaches. Each is limited by its single-gene/single-environment foci given that most phenotypes are the product of multiple interacting genetic and environmental factors. We thus addressed these two concerns in a recently developed R package (LEGIT) for constructing G x E interaction models with latent genetic and environmental scores using alternating optimization. Herein we test, by means of computer simulation, diverse G x E models in the context of both single and multiple genes and environments. Results indicate that the RoS and competitive-confirmatory approaches were highly accurate when the sample size was large, whereas the latter performed better in small samples and for small effect sizes. The competitive-confirmatory approach generally had good accuracy (a) when effect size was moderate and N >/= 500 and (b) when effect size was large and N >/= 250, whereas RoS performed poorly. Computational tools to determine the type of G x E of multiple genes and environments are provided as extensions in our LEGIT R package. En ligne : http://dx.doi.org/10.1017/s0954579418001438 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=415 [article] Distinguishing differential susceptibility, diathesis-stress, and vantage sensitivity: Beyond the single gene and environment model [Texte imprimé et/ou numérique] / Alexia JOLICOEUR-MARTINEAU, Auteur ; Jay BELSKY, Auteur ; Eszter SZEKELY, Auteur ; Keith F. WIDAMAN, Auteur ; Michael PLUESS, Auteur ; Celia M. T. GREENWOOD, Auteur ; Ashley WAZANA, Auteur . - p.73-83. Langues : Anglais (eng) in Development and Psychopathology > 32-1 (February 2020) . - p.73-83 Mots-clés : diathesis-stress  differential-susceptibility  gene-by-environment interaction  regions of significance  vantage sensitivity Index. décimale : PER Périodiques Résumé : Currently, two main approaches exist to distinguish differential susceptibility from diathesis-stress and vantage sensitivity in Genotype x Environment interaction (G x E) research: regions of significance (RoS) and competitive-confirmatory approaches. Each is limited by its single-gene/single-environment foci given that most phenotypes are the product of multiple interacting genetic and environmental factors. We thus addressed these two concerns in a recently developed R package (LEGIT) for constructing G x E interaction models with latent genetic and environmental scores using alternating optimization. Herein we test, by means of computer simulation, diverse G x E models in the context of both single and multiple genes and environments. Results indicate that the RoS and competitive-confirmatory approaches were highly accurate when the sample size was large, whereas the latter performed better in small samples and for small effect sizes. The competitive-confirmatory approach generally had good accuracy (a) when effect size was moderate and N >/= 500 and (b) when effect size was large and N >/= 250, whereas RoS performed poorly. Computational tools to determine the type of G x E of multiple genes and environments are provided as extensions in our LEGIT R package. En ligne : http://dx.doi.org/10.1017/s0954579418001438 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=415

Negative emotionality as a candidate mediating mechanism linking prenatal maternal mood problems and offspring internalizing behaviour / Cathryn GORDON GREEN in Development and Psychopathology, 35-2 (May 2023)  

Public ISBD [article]  inDevelopment and Psychopathology > 35-2 (May 2023) . - p.604-618 Titre : Negative emotionality as a candidate mediating mechanism linking prenatal maternal mood problems and offspring internalizing behaviour Type de document : Texte imprimé et/ou numérique Auteurs : Cathryn GORDON GREEN, Auteur ; Eszter SZEKELY, Auteur ; Vanessa BABINEAU, Auteur ; Alexia JOLICOEUR-MARTINEAU, Auteur ; Andrée-Anne BOUVETTE-TURCOT, Auteur ; Klaus MINDE, Auteur ; Roberto SASSI, Auteur ; Leslie ATKINSON, Auteur ; James L. KENNEDY, Auteur ; Meir STEINER, Auteur ; John LYDON, Auteur ; Helene GAUDREAU, Auteur ; Jacob A. BURACK, Auteur ; Catherine HERBA, Auteur ; Marie-Helene PENNESTRI, Auteur ; Robert LEVITAN, Auteur ; Michael J. MEANEY, Auteur ; Ashley WAZANA, Auteur Article en page(s) : p.604-618 Langues : Anglais (eng) Mots-clés : developmental pathways  internalizing problems  negative emotionality  pregnancy-specific anxiety  prenatal depression  prenatal programming Index. décimale : PER Périodiques Résumé : Negative emotionality (NE) was evaluated as a candidate mechanism linking prenatal maternal affective symptoms and offspring internalizing problems during the preschool/early school age period. The participants were 335 mother-infant dyads from the Maternal Adversity, Vulnerability and Neurodevelopment project. A Confirmatory Bifactor Analysis (CFA) based on self-report measures of prenatal depression and pregnancy-specific anxiety generated a general factor representing overlapping symptoms of prenatal maternal psychopathology and four distinct symptom factors representing pregnancy-specific anxiety, negative affect, anhedonia and somatization. NE was rated by the mother at 18 and 36 months. CFA based on measures of father, mother, child-rated measures and a semistructured interview generated a general internalizing factor representing overlapping symptoms of child internalizing psychopathology accounting for the unique contribution of each informant. Path analyses revealed significant relationships among the general maternal affective psychopathology, the pregnancy- specific anxiety, and the child internalizing factors. Child NE mediated only the relationship between pregnancy-specific anxiety and the child internalizing factors. We highlighted the conditions in which prenatal maternal affective symptoms predicts child internalizing problems emerging early in development, including consideration of different mechanistic pathways for different maternal prenatal symptom presentations and child temperament. En ligne : http://dx.doi.org/10.1017/S0954579421001747 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=504 [article] Negative emotionality as a candidate mediating mechanism linking prenatal maternal mood problems and offspring internalizing behaviour [Texte imprimé et/ou numérique] / Cathryn GORDON GREEN, Auteur ; Eszter SZEKELY, Auteur ; Vanessa BABINEAU, Auteur ; Alexia JOLICOEUR-MARTINEAU, Auteur ; Andrée-Anne BOUVETTE-TURCOT, Auteur ; Klaus MINDE, Auteur ; Roberto SASSI, Auteur ; Leslie ATKINSON, Auteur ; James L. KENNEDY, Auteur ; Meir STEINER, Auteur ; John LYDON, Auteur ; Helene GAUDREAU, Auteur ; Jacob A. BURACK, Auteur ; Catherine HERBA, Auteur ; Marie-Helene PENNESTRI, Auteur ; Robert LEVITAN, Auteur ; Michael J. MEANEY, Auteur ; Ashley WAZANA, Auteur . - p.604-618. Langues : Anglais (eng) in Development and Psychopathology > 35-2 (May 2023) . - p.604-618 Mots-clés : developmental pathways  internalizing problems  negative emotionality  pregnancy-specific anxiety  prenatal depression  prenatal programming Index. décimale : PER Périodiques Résumé : Negative emotionality (NE) was evaluated as a candidate mechanism linking prenatal maternal affective symptoms and offspring internalizing problems during the preschool/early school age period. The participants were 335 mother-infant dyads from the Maternal Adversity, Vulnerability and Neurodevelopment project. A Confirmatory Bifactor Analysis (CFA) based on self-report measures of prenatal depression and pregnancy-specific anxiety generated a general factor representing overlapping symptoms of prenatal maternal psychopathology and four distinct symptom factors representing pregnancy-specific anxiety, negative affect, anhedonia and somatization. NE was rated by the mother at 18 and 36 months. CFA based on measures of father, mother, child-rated measures and a semistructured interview generated a general internalizing factor representing overlapping symptoms of child internalizing psychopathology accounting for the unique contribution of each informant. Path analyses revealed significant relationships among the general maternal affective psychopathology, the pregnancy- specific anxiety, and the child internalizing factors. Child NE mediated only the relationship between pregnancy-specific anxiety and the child internalizing factors. We highlighted the conditions in which prenatal maternal affective symptoms predicts child internalizing problems emerging early in development, including consideration of different mechanistic pathways for different maternal prenatal symptom presentations and child temperament. En ligne : http://dx.doi.org/10.1017/S0954579421001747 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=504

Prenatal maternal depression and child serotonin transporter linked polymorphic region (5-HTTLPR) and dopamine receptor D4 (DRD4) genotype predict negative emotionality from 3 to 36 months / Cathryn Gordon GREEN in Development and Psychopathology, 29-3 (August 2017)  

Public ISBD [article]  inDevelopment and Psychopathology > 29-3 (August 2017) . - p.901-917 Titre : Prenatal maternal depression and child serotonin transporter linked polymorphic region (5-HTTLPR) and dopamine receptor D4 (DRD4) genotype predict negative emotionality from 3 to 36 months Type de document : Texte imprimé et/ou numérique Auteurs : Cathryn Gordon GREEN, Auteur ; Vanessa BABINEAU, Auteur ; Alexia JOLICOEUR-MARTINEAU, Auteur ; Andrée-Anne BOUVETTE-TURCOT, Auteur ; Klaus MINDE, Auteur ; Roberto SASSI, Auteur ; Martin ST-ANDRÉ, Auteur ; Normand J. CARREY, Auteur ; Leslie ATKINSON, Auteur ; James L. KENNEDY, Auteur ; Meir STEINER, Auteur ; John LYDON, Auteur ; Helene GAUDREAU, Auteur ; Jacob A. BURACK, Auteur ; Robert LEVITAN, Auteur ; Michael J. MEANEY, Auteur ; Ashley WAZANA, Auteur Article en page(s) : p.901-917 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Abstract Prenatal maternal depression and a multilocus genetic profile of two susceptibility genes implicated in the stress response were examined in an interaction model predicting negative emotionality in the first 3 years. In 179 mother–infant dyads from the Maternal Adversity, Vulnerability, and Neurodevelopment cohort, prenatal depression (Center for Epidemiologic Studies Depressions Scale) was assessed at 24 to 36 weeks. The multilocus genetic profile score consisted of the number of susceptibility alleles from the serotonin transporter linked polymorphic region gene (5-HTTLPR): no long-rs25531(A) (LA: short/short, short/long-rs25531(G) [LG], or LG/LG] vs. any LA) and the dopamine receptor D4 gene (six to eight repeats vs. two to five repeats). Negative emotionality was extracted from the Infant Behaviour Questionnaire—Revised at 3 and 6 months and the Early Child Behavior Questionnaire at 18 and 36 months. Mixed and confirmatory regression analyses indicated that prenatal depression and the multilocus genetic profile interacted to predict negative emotionality from 3 to 36 months. The results were characterized by a differential susceptibility model at 3 and 6 months and by a diathesis–stress model at 36 months. En ligne : http://dx.doi.org/10.1017/s0954579416000560 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=312 [article] Prenatal maternal depression and child serotonin transporter linked polymorphic region (5-HTTLPR) and dopamine receptor D4 (DRD4) genotype predict negative emotionality from 3 to 36 months [Texte imprimé et/ou numérique] / Cathryn Gordon GREEN, Auteur ; Vanessa BABINEAU, Auteur ; Alexia JOLICOEUR-MARTINEAU, Auteur ; Andrée-Anne BOUVETTE-TURCOT, Auteur ; Klaus MINDE, Auteur ; Roberto SASSI, Auteur ; Martin ST-ANDRÉ, Auteur ; Normand J. CARREY, Auteur ; Leslie ATKINSON, Auteur ; James L. KENNEDY, Auteur ; Meir STEINER, Auteur ; John LYDON, Auteur ; Helene GAUDREAU, Auteur ; Jacob A. BURACK, Auteur ; Robert LEVITAN, Auteur ; Michael J. MEANEY, Auteur ; Ashley WAZANA, Auteur . - p.901-917. Langues : Anglais (eng) in Development and Psychopathology > 29-3 (August 2017) . - p.901-917 Index. décimale : PER Périodiques Résumé : Abstract Prenatal maternal depression and a multilocus genetic profile of two susceptibility genes implicated in the stress response were examined in an interaction model predicting negative emotionality in the first 3 years. In 179 mother–infant dyads from the Maternal Adversity, Vulnerability, and Neurodevelopment cohort, prenatal depression (Center for Epidemiologic Studies Depressions Scale) was assessed at 24 to 36 weeks. The multilocus genetic profile score consisted of the number of susceptibility alleles from the serotonin transporter linked polymorphic region gene (5-HTTLPR): no long-rs25531(A) (LA: short/short, short/long-rs25531(G) [LG], or LG/LG] vs. any LA) and the dopamine receptor D4 gene (six to eight repeats vs. two to five repeats). Negative emotionality was extracted from the Infant Behaviour Questionnaire—Revised at 3 and 6 months and the Early Child Behavior Questionnaire at 18 and 36 months. Mixed and confirmatory regression analyses indicated that prenatal depression and the multilocus genetic profile interacted to predict negative emotionality from 3 to 36 months. The results were characterized by a differential susceptibility model at 3 and 6 months and by a diathesis–stress model at 36 months. En ligne : http://dx.doi.org/10.1017/s0954579416000560 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=312

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