Disentangling the influences of parental genetics on offspring's cognition, education, and psychopathology via genetic and phenotypic pathways / Luiza K. AXELRUD in Journal of Child Psychology and Psychiatry, 64-3 (March 2023)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 64-3 (March 2023) . - p.408-416 Titre : Disentangling the influences of parental genetics on offspring's cognition, education, and psychopathology via genetic and phenotypic pathways Type de document : texte imprimé Auteurs : Luiza K. AXELRUD, Auteur ; Mauricio S. HOFFMANN, Auteur ; Daniel E. VOSBERG, Auteur ; Marcos SANTORO, Auteur ; Pedro M. PAN, Auteur ; Ary GADELHA, Auteur ; Sintia I. BELANGERO, Auteur ; Euripedes Constantino MIGUEL, Auteur ; Jean SHIN, Auteur ; Anita THAPAR, Auteur ; Jordan W. SMOLLER, Auteur ; Zdenka PAUSOVA, Auteur ; Luis Augusto ROHDE, Auteur ; Matthew C. KELLER, Auteur ; Tomáš PAUS, Auteur ; Giovanni A. SALUM, Auteur Article en page(s) : p.408-416 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background Specific pathways of intergenerational transmission of behavioral traits remain unclear. Here, we aim to investigate how parental genetics influence offspring cognition, educational attainment, and psychopathology in youth. Methods Participants for the discovery sample were 2,189 offspring (aged 6-14 years), 1898 mothers and 1,017 fathers who underwent genotyping, psychiatric, and cognitive assessments. We calculated polygenic scores (PGS) for cognition, educational attainment, attention-deficit hyperactivity disorder (ADHD), and schizophrenia for the trios. Phenotypes studied included educational and cognitive measures, ADHD and psychotic symptoms. We used a stepwise approach and multiple mediation models to analyze the effect of parental PGS on offspring traits via offspring PGS and parental phenotype. Significant results were replicated in a sample of 1,029 adolescents, 363 mothers, and 307 fathers. Results Maternal and paternal PGS for cognition influenced offspring general intelligence and executive function via offspring PGS (genetic pathway) and parental education (phenotypic pathway). Similar results were found for parental PGS for educational attainment and offspring reading and writing skills. These pathways fully explained associations between parental PGS and offspring phenotypes, without residual direct association. Associations with maternal, but not paternal, PGS were replicated. No associations were found between parental PGS for psychopathology and offspring specific symptoms. Conclusions Our findings indicate that parental genetics influences offspring cognition and educational attainment by genetic and phenotypic pathways, suggesting the expression of parental phenotypes partially explain the association between parental genetic risk and offspring outcomes. Multiple mediations might represent an effective approach to disentangle distinct pathways for intergenerational transmission of behavioral traits. En ligne : https://doi.org/10.1111/jcpp.13708 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=493 [article] Disentangling the influences of parental genetics on offspring's cognition, education, and psychopathology via genetic and phenotypic pathways [texte imprimé] / Luiza K. AXELRUD, Auteur ; Mauricio S. HOFFMANN, Auteur ; Daniel E. VOSBERG, Auteur ; Marcos SANTORO, Auteur ; Pedro M. PAN, Auteur ; Ary GADELHA, Auteur ; Sintia I. BELANGERO, Auteur ; Euripedes Constantino MIGUEL, Auteur ; Jean SHIN, Auteur ; Anita THAPAR, Auteur ; Jordan W. SMOLLER, Auteur ; Zdenka PAUSOVA, Auteur ; Luis Augusto ROHDE, Auteur ; Matthew C. KELLER, Auteur ; Tomáš PAUS, Auteur ; Giovanni A. SALUM, Auteur . - p.408-416. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 64-3 (March 2023) . - p.408-416 Index. décimale : PER Périodiques Résumé : Background Specific pathways of intergenerational transmission of behavioral traits remain unclear. Here, we aim to investigate how parental genetics influence offspring cognition, educational attainment, and psychopathology in youth. Methods Participants for the discovery sample were 2,189 offspring (aged 6-14 years), 1898 mothers and 1,017 fathers who underwent genotyping, psychiatric, and cognitive assessments. We calculated polygenic scores (PGS) for cognition, educational attainment, attention-deficit hyperactivity disorder (ADHD), and schizophrenia for the trios. Phenotypes studied included educational and cognitive measures, ADHD and psychotic symptoms. We used a stepwise approach and multiple mediation models to analyze the effect of parental PGS on offspring traits via offspring PGS and parental phenotype. Significant results were replicated in a sample of 1,029 adolescents, 363 mothers, and 307 fathers. Results Maternal and paternal PGS for cognition influenced offspring general intelligence and executive function via offspring PGS (genetic pathway) and parental education (phenotypic pathway). Similar results were found for parental PGS for educational attainment and offspring reading and writing skills. These pathways fully explained associations between parental PGS and offspring phenotypes, without residual direct association. Associations with maternal, but not paternal, PGS were replicated. No associations were found between parental PGS for psychopathology and offspring specific symptoms. Conclusions Our findings indicate that parental genetics influences offspring cognition and educational attainment by genetic and phenotypic pathways, suggesting the expression of parental phenotypes partially explain the association between parental genetic risk and offspring outcomes. Multiple mediations might represent an effective approach to disentangle distinct pathways for intergenerational transmission of behavioral traits. En ligne : https://doi.org/10.1111/jcpp.13708 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=493

Heterotypic trajectories of dimensional psychopathology across the lifespan: the case of youth-onset attention deficit/hyperactivity disorder / Arthur Gus MANFRO in Journal of Child Psychology and Psychiatry, 60-5 (May 2019)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 60-5 (May 2019) . - p.533-544 Titre : Heterotypic trajectories of dimensional psychopathology across the lifespan: the case of youth-onset attention deficit/hyperactivity disorder Type de document : texte imprimé Auteurs : Arthur Gus MANFRO, Auteur ; Marcos SANTORO, Auteur ; Guilherme V. POLANCZYK, Auteur ; Ary GADELHA, Auteur ; Pedro M. PAN, Auteur ; Rodrigo Affonseca BRESSAN, Auteur ; Elisa BRIETZKE, Auteur ; Fernanda TALARICO, Auteur ; Sintia BELANGERO, Auteur ; Luis Augusto ROHDE, Auteur ; Giovanni A. SALUM, Auteur Article en page(s) : p.533-544 Langues : Anglais (eng) Mots-clés : Youth-onset  cognition  executive function  p-factor  polygenic risk scores Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent studies have demonstrated the existence of a distinct late-onset attention deficit/hyperactivity disorder (ADHD) trajectory. Our objective is to test if there are distinct ADHD trajectories regarding age of onset from childhood to adolescence and to compare clinical manifestations, cognitive functions and genetic risk for ADHD among distinct longitudinal groups. METHOD: Nine hundred and twenty four children and adolescents from the community participated in the study. We compared clinical, cognitive features and genetic risk among four groups of participants: (a) childhood-limited, (b) youth-onset, (c) childhood-onset with youth persistence, and (d) community comparisons without ADHD. Symptomatic and diagnostic assessments were performed using the Development and Well-Being Behavior Assessment, the Strengths and Difficulties Questionnaire, and the Child Behavior Checklist. Cognitive functions were measured using a battery of standardized tests. Genetic risk for ADHD was calculating using summary statistics from the Psychiatric Genomics Consortium. RESULTS: Half of the adolescents (52%) with ADHD had their symptom onset in adolescence. The impairment level of this group in adolescence is similar to the persistent group. Despite not having ADHD, the youth-onset group already presented in childhood more symptoms from other domains of psychopathology, higher shared variance in psychiatric symptomatology (p-factor), school impairment, and executive dysfunctions than community comparisons. Furthermore, the youth-onset group presented lower levels of genetic risk for ADHD compared to other cases. CONCLUSIONS: A significant proportion of adolescents with ADHD were youth-onset cases and presented similar impairment levels as those cases with early-onset ADHD. The presence of cognitive impairments and higher levels of clinical symptoms in the youth-onset group already at childhood speaks in favor of a heterotypic trajectory of psychopathology suggesting that youth-onset ADHD might be an artificial consequence of categorizing dimensional psychopathology into discrete diagnostic groups. En ligne : http://dx.doi.org/10.1111/jcpp.12987 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=392 [article] Heterotypic trajectories of dimensional psychopathology across the lifespan: the case of youth-onset attention deficit/hyperactivity disorder [texte imprimé] / Arthur Gus MANFRO, Auteur ; Marcos SANTORO, Auteur ; Guilherme V. POLANCZYK, Auteur ; Ary GADELHA, Auteur ; Pedro M. PAN, Auteur ; Rodrigo Affonseca BRESSAN, Auteur ; Elisa BRIETZKE, Auteur ; Fernanda TALARICO, Auteur ; Sintia BELANGERO, Auteur ; Luis Augusto ROHDE, Auteur ; Giovanni A. SALUM, Auteur . - p.533-544. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 60-5 (May 2019) . - p.533-544 Mots-clés : Youth-onset  cognition  executive function  p-factor  polygenic risk scores Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent studies have demonstrated the existence of a distinct late-onset attention deficit/hyperactivity disorder (ADHD) trajectory. Our objective is to test if there are distinct ADHD trajectories regarding age of onset from childhood to adolescence and to compare clinical manifestations, cognitive functions and genetic risk for ADHD among distinct longitudinal groups. METHOD: Nine hundred and twenty four children and adolescents from the community participated in the study. We compared clinical, cognitive features and genetic risk among four groups of participants: (a) childhood-limited, (b) youth-onset, (c) childhood-onset with youth persistence, and (d) community comparisons without ADHD. Symptomatic and diagnostic assessments were performed using the Development and Well-Being Behavior Assessment, the Strengths and Difficulties Questionnaire, and the Child Behavior Checklist. Cognitive functions were measured using a battery of standardized tests. Genetic risk for ADHD was calculating using summary statistics from the Psychiatric Genomics Consortium. RESULTS: Half of the adolescents (52%) with ADHD had their symptom onset in adolescence. The impairment level of this group in adolescence is similar to the persistent group. Despite not having ADHD, the youth-onset group already presented in childhood more symptoms from other domains of psychopathology, higher shared variance in psychiatric symptomatology (p-factor), school impairment, and executive dysfunctions than community comparisons. Furthermore, the youth-onset group presented lower levels of genetic risk for ADHD compared to other cases. CONCLUSIONS: A significant proportion of adolescents with ADHD were youth-onset cases and presented similar impairment levels as those cases with early-onset ADHD. The presence of cognitive impairments and higher levels of clinical symptoms in the youth-onset group already at childhood speaks in favor of a heterotypic trajectory of psychopathology suggesting that youth-onset ADHD might be an artificial consequence of categorizing dimensional psychopathology into discrete diagnostic groups. En ligne : http://dx.doi.org/10.1111/jcpp.12987 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=392

Replication of a predictive model for youth ADHD in an independent sample from a developing country / Cezar H. LORENZI in Journal of Child Psychology and Psychiatry, 64-1 (January 2023)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 64-1 (January 2023) . - p.167-174 Titre : Replication of a predictive model for youth ADHD in an independent sample from a developing country Type de document : texte imprimé Auteurs : Cezar H. LORENZI, Auteur ; Douglas TEIXEIRA LEFFA, Auteur ; Rodrigo Affonseca BRESSAN, Auteur ; Sintia I. BELANGERO, Auteur ; Ary GADELHA, Auteur ; Marcos SANTORO, Auteur ; Giovanni A. SALUM, Auteur ; Luis Augusto ROHDE, Auteur ; Arthur CAYE, Auteur Article en page(s) : p.167-174 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background Very few predictive models in Psychiatry had their performance validated in independent external samples. A previously developed multivariable demographic model for attention-deficit/hyperactivity disorder (ADHD) accurately predicted young adulthood ADHD using clinical and demographical information collected in childhood in three samples from developed countries, but failed to replicate its performance in a sample from a developing country. Furthermore, consolidated risk factors for ADHD were not included among its predictors. Methods Participants were 1905 children and adolescents from a community-based sample and followed from ages 6 to 14 years at baseline to ages 14 to 23 years (mean age 18) at follow-up. We applied the intercept and weights of the original model to the data, calculating the predicted probability of each participant according to the set of predictors collected in childhood, and compared the estimates with the actual outcome (ADHD) collected during adolescence and young adulthood. We explored the performance of the original model, and of models including novel predictors (prematurity, family history of ADHD, and polygenic risk score for ADHD). Results The observed area under the curve of the original model was .76 (95% Confidence Interval .70 to .82). The multivariable demographical model outperformed single variable models using only prematurity, family history, or the ADHD PRS. Adding either of these variables, or all at once, did not improve the performance of the original demographical model. Conclusions Our findings suggest that the originally developed ADHD predictive model is suitable for use in different settings for clinical and research purposes. En ligne : https://doi.org/10.1111/jcpp.13682 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=490 [article] Replication of a predictive model for youth ADHD in an independent sample from a developing country [texte imprimé] / Cezar H. LORENZI, Auteur ; Douglas TEIXEIRA LEFFA, Auteur ; Rodrigo Affonseca BRESSAN, Auteur ; Sintia I. BELANGERO, Auteur ; Ary GADELHA, Auteur ; Marcos SANTORO, Auteur ; Giovanni A. SALUM, Auteur ; Luis Augusto ROHDE, Auteur ; Arthur CAYE, Auteur . - p.167-174. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 64-1 (January 2023) . - p.167-174 Index. décimale : PER Périodiques Résumé : Background Very few predictive models in Psychiatry had their performance validated in independent external samples. A previously developed multivariable demographic model for attention-deficit/hyperactivity disorder (ADHD) accurately predicted young adulthood ADHD using clinical and demographical information collected in childhood in three samples from developed countries, but failed to replicate its performance in a sample from a developing country. Furthermore, consolidated risk factors for ADHD were not included among its predictors. Methods Participants were 1905 children and adolescents from a community-based sample and followed from ages 6 to 14 years at baseline to ages 14 to 23 years (mean age 18) at follow-up. We applied the intercept and weights of the original model to the data, calculating the predicted probability of each participant according to the set of predictors collected in childhood, and compared the estimates with the actual outcome (ADHD) collected during adolescence and young adulthood. We explored the performance of the original model, and of models including novel predictors (prematurity, family history of ADHD, and polygenic risk score for ADHD). Results The observed area under the curve of the original model was .76 (95% Confidence Interval .70 to .82). The multivariable demographical model outperformed single variable models using only prematurity, family history, or the ADHD PRS. Adding either of these variables, or all at once, did not improve the performance of the original demographical model. Conclusions Our findings suggest that the originally developed ADHD predictive model is suitable for use in different settings for clinical and research purposes. En ligne : https://doi.org/10.1111/jcpp.13682 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=490

The synergistic effect of genetic and environmental factors in the development of attention-deficit/hyperactivity disorder symptoms in children and adolescents / Douglas Teixeira LEFFA in Development and Psychopathology, 36-3 (August 2024)  

Public ISBD [article]  inDevelopment and Psychopathology > 36-3 (August 2024) . - p.1134-1144 Titre : The synergistic effect of genetic and environmental factors in the development of attention-deficit/hyperactivity disorder symptoms in children and adolescents Type de document : texte imprimé Auteurs : Douglas Teixeira LEFFA, Auteur ; Arthur CAYE, Auteur ; Sintia I. BELANGERO, Auteur ; Ary GADELHA, Auteur ; Pedro M. PAN, Auteur ; Giovanni A. SALUM, Auteur ; Luis Augusto ROHDE, Auteur Article en page(s) : p.1134-1144 Langues : Anglais (eng) Mots-clés : ADHD  environment  epidemiology  genetics  risk factors Index. décimale : PER Périodiques Résumé : Gene-environment interactions (GxE) have been increasingly explored in psychiatry but with low replication rates. Attention-deficit/hyperactivity disorder (ADHD) is a suitable candidate for studying GxE due to its high heritability and well-defined environmental risk factors. Here, we explored GxE using polygenic risk score (PRS) to represent the genetic liability to ADHD (ADHD-PRS) and environmental risk score (ERS) to represent the combined effects of environmental risk factors. We analyzed longitudinal data of 2,046 individuals (6-14 years of age at baseline and 14-23 at the last follow-up) from the Brazilian High-Risk Cohort Study for Psychiatric Disorders. Psychiatric evaluation included the Child Behavior Checklist and the Strength and Difficulties Questionnaire. Statistical analyses were performed using mixed-effects models. We observed statistically significant interactions between ADHD-PRS and ERS, suggesting that environmental and genetic factors act synergistically in the development of ADHD symptoms. These effects were not present for depression or anxiety symptoms. No evidence of GxE correlation was detected. Mechanistically, our findings suggest that environmental stressors modulate the genetic risk for ADHD. Future studies should investigate whether the reduction of environmental risks can prevent the development of symptoms of ADHD, especially in children with a family history of the disorder. En ligne : https://dx.doi.org/10.1017/S0954579423000366 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] The synergistic effect of genetic and environmental factors in the development of attention-deficit/hyperactivity disorder symptoms in children and adolescents [texte imprimé] / Douglas Teixeira LEFFA, Auteur ; Arthur CAYE, Auteur ; Sintia I. BELANGERO, Auteur ; Ary GADELHA, Auteur ; Pedro M. PAN, Auteur ; Giovanni A. SALUM, Auteur ; Luis Augusto ROHDE, Auteur . - p.1134-1144. Langues : Anglais (eng) in Development and Psychopathology > 36-3 (August 2024) . - p.1134-1144 Mots-clés : ADHD  environment  epidemiology  genetics  risk factors Index. décimale : PER Périodiques Résumé : Gene-environment interactions (GxE) have been increasingly explored in psychiatry but with low replication rates. Attention-deficit/hyperactivity disorder (ADHD) is a suitable candidate for studying GxE due to its high heritability and well-defined environmental risk factors. Here, we explored GxE using polygenic risk score (PRS) to represent the genetic liability to ADHD (ADHD-PRS) and environmental risk score (ERS) to represent the combined effects of environmental risk factors. We analyzed longitudinal data of 2,046 individuals (6-14 years of age at baseline and 14-23 at the last follow-up) from the Brazilian High-Risk Cohort Study for Psychiatric Disorders. Psychiatric evaluation included the Child Behavior Checklist and the Strength and Difficulties Questionnaire. Statistical analyses were performed using mixed-effects models. We observed statistically significant interactions between ADHD-PRS and ERS, suggesting that environmental and genetic factors act synergistically in the development of ADHD symptoms. These effects were not present for depression or anxiety symptoms. No evidence of GxE correlation was detected. Mechanistically, our findings suggest that environmental stressors modulate the genetic risk for ADHD. Future studies should investigate whether the reduction of environmental risks can prevent the development of symptoms of ADHD, especially in children with a family history of the disorder. En ligne : https://dx.doi.org/10.1017/S0954579423000366 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

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