Cumulative prenatal exposure to adversity reveals associations with a broad range of neurodevelopmental outcomes that are moderated by a novel, biologically informed polygenetic score based on the serotonin transporter solute carrier family C6, member 4 (SLC6A4) gene expression / Patricia P. SILVEIRA in Development and Psychopathology, 29-5 (December 2017)  

Public ISBD [article]  inDevelopment and Psychopathology > 29-5 (December 2017) . - p.1601-1617 Titre : Cumulative prenatal exposure to adversity reveals associations with a broad range of neurodevelopmental outcomes that are moderated by a novel, biologically informed polygenetic score based on the serotonin transporter solute carrier family C6, member 4 (SLC6A4) gene expression Type de document : texte imprimé Auteurs : Patricia P. SILVEIRA, Auteur ; Irina POKHVISNEVA, Auteur ; Carine PARENT, Auteur ; Shirong CAI, Auteur ; Anu Sathyan Sathyapalan REMA, Auteur ; Birit F.P. BROEKMAN, Auteur ; Anne RIFKIN-GRABOI, Auteur ; Michael PLUESS, Auteur ; Kieran J. O'DONNELL, Auteur ; Michael J. MEANEY, Auteur Article en page(s) : p.1601-1617 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : While many studies focus on the association between early life adversity and the later risk for psychopathology, few simultaneously explore diverse forms of environmental adversity. Moreover, those studies that examined the cumulative impact of early life adversity focus uniquely on postnatal influences. The objective of this study was to focus on the fetal period of development to construct and validate a cumulative prenatal adversity score in relation to a wide range of neurodevelopmental outcomes. We also examined the interaction of this adversity score with a biologically informed genetic score based on the serotonin transporter gene. Prenatal adversities were computed in two community birth cohorts using information on health during pregnancy, birth weight, gestational age, income, domestic violence/sexual abuse, marital strain, as well as maternal smoking, anxiety, and depression. A genetic score based on genes coexpressed with the serotonin transporter in the amygdala, hippocampus, and prefrontal cortex during prenatal life was constructed with an emphasis on functionally relevant single nucleotide polymorphisms, that is, expression quantitative trait loci. Prenatal adversities predicted a wide range of developmental and behavioral alterations in children as young as 2 years of age in both cohorts. There were interactions between the genetic score and adversities for several domains of the Child Behavior Checklist (CBCL), with pervasive developmental problems remaining significant adjustment for multiple comparisons. Scores combining different prenatal adverse exposures predict childhood behavior and interact with the genetic background to influence the risk for psychopathology. En ligne : http://dx.doi.org/10.1017/S0954579417001262 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=323 [article] Cumulative prenatal exposure to adversity reveals associations with a broad range of neurodevelopmental outcomes that are moderated by a novel, biologically informed polygenetic score based on the serotonin transporter solute carrier family C6, member 4 (SLC6A4) gene expression [texte imprimé] / Patricia P. SILVEIRA, Auteur ; Irina POKHVISNEVA, Auteur ; Carine PARENT, Auteur ; Shirong CAI, Auteur ; Anu Sathyan Sathyapalan REMA, Auteur ; Birit F.P. BROEKMAN, Auteur ; Anne RIFKIN-GRABOI, Auteur ; Michael PLUESS, Auteur ; Kieran J. O'DONNELL, Auteur ; Michael J. MEANEY, Auteur . - p.1601-1617. Langues : Anglais (eng) in Development and Psychopathology > 29-5 (December 2017) . - p.1601-1617 Index. décimale : PER Périodiques Résumé : While many studies focus on the association between early life adversity and the later risk for psychopathology, few simultaneously explore diverse forms of environmental adversity. Moreover, those studies that examined the cumulative impact of early life adversity focus uniquely on postnatal influences. The objective of this study was to focus on the fetal period of development to construct and validate a cumulative prenatal adversity score in relation to a wide range of neurodevelopmental outcomes. We also examined the interaction of this adversity score with a biologically informed genetic score based on the serotonin transporter gene. Prenatal adversities were computed in two community birth cohorts using information on health during pregnancy, birth weight, gestational age, income, domestic violence/sexual abuse, marital strain, as well as maternal smoking, anxiety, and depression. A genetic score based on genes coexpressed with the serotonin transporter in the amygdala, hippocampus, and prefrontal cortex during prenatal life was constructed with an emphasis on functionally relevant single nucleotide polymorphisms, that is, expression quantitative trait loci. Prenatal adversities predicted a wide range of developmental and behavioral alterations in children as young as 2 years of age in both cohorts. There were interactions between the genetic score and adversities for several domains of the Child Behavior Checklist (CBCL), with pervasive developmental problems remaining significant adjustment for multiple comparisons. Scores combining different prenatal adverse exposures predict childhood behavior and interact with the genetic background to influence the risk for psychopathology. En ligne : http://dx.doi.org/10.1017/S0954579417001262 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=323

A DRD4 gene by maternal sensitivity interaction predicts risk for overweight or obesity in two independent cohorts of preschool children / Robert LEVITAN in Journal of Child Psychology and Psychiatry, 58-2 (February 2017)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 58-2 (February 2017) . - p.180-188 Titre : A DRD4 gene by maternal sensitivity interaction predicts risk for overweight or obesity in two independent cohorts of preschool children Type de document : texte imprimé Auteurs : Robert LEVITAN, Auteur ; Pauline W. JANSEN, Auteur ; Barbara WENDLAND, Auteur ; Henning TIEMEIER, Auteur ; Vincent W.V. JADDOE, Auteur ; Patricia P. SILVEIRA, Auteur ; James L. KENNEDY, Auteur ; Leslie ATKINSON, Auteur ; Alison S. FLEMING, Auteur ; Marla SOKOLOWSKI, Auteur ; Helene GAUDREAU, Auteur ; Meir STEINER, Auteur ; Laurette DUBE, Auteur ; Jill HAMILTON, Auteur ; Ellen MOSS, Auteur ; Ashley WAZANA, Auteur ; Michael J. MEANEY, Auteur Année de publication : 2017 Article en page(s) : p.180-188 Langues : Anglais (eng) Mots-clés : Maternal sensitivity  DRD4  obesity  sex differences Index. décimale : PER Périodiques Résumé : Background Recent evidence suggests that early exposure to low maternal sensitivity is a risk factor for obesity in children and adolescents. A separate line of study shows that the seven-repeat (7R) allele of the dopamine-4 receptor gene (DRD4) increases susceptibility to environmental factors including maternal sensitivity. The current study integrates these lines of work by examining whether preschoolers carrying the 7R allele are more vulnerable to low maternal sensitivity as it relates to overweight/obesity risk. Method The Maternal Adversity Vulnerability and Neurodevelopment (MAVAN) project in Canada was used as the discovery cohort (N = 203), while the Generation R study in the Netherlands was used as a replication sample (N = 270). Regression models to predict both continuous BMI z-scores and membership in any higher BMI category based on established World Health Organization (WHO) cutoffs for 48 months of age were completed. Results In both cohorts, there was a significant maternal sensitivity by DRD4 by sex interaction predicting higher body mass indices and/or obesity risk. As hypothesized, post hoc testing revealed an inverse relationship between maternal sensitivity and body mass indices in 7R allele carriers relative to noncarriers. This finding was strongest in girls in the Canadian cohort and in boys in the Dutch cohort. Conclusions Many children who carry the 7R allele of DRD4 appear to be more influenced by maternal sensitivity as it relates to overweight/obesity risk, consistent with a plasticity effect. Given the relatively small sample sizes available for these analyses, further replications will be needed to confirm and extend these results. En ligne : http://dx.doi.org/10.1111/jcpp.12646 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=299 [article] A DRD4 gene by maternal sensitivity interaction predicts risk for overweight or obesity in two independent cohorts of preschool children [texte imprimé] / Robert LEVITAN, Auteur ; Pauline W. JANSEN, Auteur ; Barbara WENDLAND, Auteur ; Henning TIEMEIER, Auteur ; Vincent W.V. JADDOE, Auteur ; Patricia P. SILVEIRA, Auteur ; James L. KENNEDY, Auteur ; Leslie ATKINSON, Auteur ; Alison S. FLEMING, Auteur ; Marla SOKOLOWSKI, Auteur ; Helene GAUDREAU, Auteur ; Meir STEINER, Auteur ; Laurette DUBE, Auteur ; Jill HAMILTON, Auteur ; Ellen MOSS, Auteur ; Ashley WAZANA, Auteur ; Michael J. MEANEY, Auteur . - 2017 . - p.180-188. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 58-2 (February 2017) . - p.180-188 Mots-clés : Maternal sensitivity  DRD4  obesity  sex differences Index. décimale : PER Périodiques Résumé : Background Recent evidence suggests that early exposure to low maternal sensitivity is a risk factor for obesity in children and adolescents. A separate line of study shows that the seven-repeat (7R) allele of the dopamine-4 receptor gene (DRD4) increases susceptibility to environmental factors including maternal sensitivity. The current study integrates these lines of work by examining whether preschoolers carrying the 7R allele are more vulnerable to low maternal sensitivity as it relates to overweight/obesity risk. Method The Maternal Adversity Vulnerability and Neurodevelopment (MAVAN) project in Canada was used as the discovery cohort (N = 203), while the Generation R study in the Netherlands was used as a replication sample (N = 270). Regression models to predict both continuous BMI z-scores and membership in any higher BMI category based on established World Health Organization (WHO) cutoffs for 48 months of age were completed. Results In both cohorts, there was a significant maternal sensitivity by DRD4 by sex interaction predicting higher body mass indices and/or obesity risk. As hypothesized, post hoc testing revealed an inverse relationship between maternal sensitivity and body mass indices in 7R allele carriers relative to noncarriers. This finding was strongest in girls in the Canadian cohort and in boys in the Dutch cohort. Conclusions Many children who carry the 7R allele of DRD4 appear to be more influenced by maternal sensitivity as it relates to overweight/obesity risk, consistent with a plasticity effect. Given the relatively small sample sizes available for these analyses, further replications will be needed to confirm and extend these results. En ligne : http://dx.doi.org/10.1111/jcpp.12646 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=299

Maternal antenatal depression and child mental health: Moderation by genomic risk for attention-deficit/hyperactivity disorder / Lawrence M. CHEN in Development and Psychopathology, 32-5 (December 2020)  

Public ISBD [article]  inDevelopment and Psychopathology > 32-5 (December 2020) . - p.1810-1821 Titre : Maternal antenatal depression and child mental health: Moderation by genomic risk for attention-deficit/hyperactivity disorder Type de document : texte imprimé Auteurs : Lawrence M. CHEN, Auteur ; Marieke S. TOLLENAAR, Auteur ; Shantala A. HARI DASS, Auteur ; Andrée-Anne BOUVETTE-TURCOT, Auteur ; Irina POKHVISNEVA, Auteur ; Helene GAUDREAU, Auteur ; Carine PARENT, Auteur ; Josie DIORIO, Auteur ; Lisa M. MCEWEN, Auteur ; Julia L. MACISAAC, Auteur ; Michael S. KOBOR, Auteur ; Roseriet BEIJERS, Auteur ; Carolina DE WEERTH, Auteur ; Patricia P. SILVEIRA, Auteur ; Sherif KARAMA, Auteur ; Michael J. MEANEY, Auteur ; Kieran J. O'DONNELL, Auteur Article en page(s) : p.1810-1821 Langues : Anglais (eng) Mots-clés : *Attention Deficit Disorder with Hyperactivity/genetics  Child  Depression/genetics  Female  Genomics  Humans  Mental Health  Mothers  Pregnancy  *adhd  *child development  *gene by environment (GxE)  *perinatal mental health  *polygenic risk score Index. décimale : PER Périodiques Résumé : Maternal antenatal depression strongly influences child mental health but with considerable inter-individual variation that is, in part, linked to genotype. The challenge is to effectively capture the genotypic influence. We outline a novel approach to describe genomic susceptibility to maternal antenatal depression focusing on child emotional/behavioral difficulties. Two cohorts provided measures of maternal depression, child genetic variation, and child mental health symptoms. We constructed a conventional polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) (PRSADHD) that significantly moderated the association between maternal antenatal depression and internalizing problems at 60 months (p = 2.94 × 10-4, R2 = .18). We then constructed an interaction PRS (xPRS) based on a subset of those single nucleotide polymorphisms from the PRSADHD that most accounted for the moderation of the association between maternal antenatal depression and child outcome. The interaction between maternal antenatal depression and this xPRS accounted for a larger proportion of the variance in child emotional/behavioral problems than models based on any PRSADHD (p = 5.50 × 10-9, R2 = .27), with similar findings in the replication cohort. The xPRS was significantly enriched for genes involved in neuronal development and synaptic function. Our study illustrates a novel approach to the study of genotypic moderation on the impact of maternal antenatal depression on child mental health and highlights the utility of the xPRS approach. These findings advance our understanding of individual differences in the developmental origins of mental health. En ligne : http://dx.doi.org/10.1017/s0954579420001418 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=437 [article] Maternal antenatal depression and child mental health: Moderation by genomic risk for attention-deficit/hyperactivity disorder [texte imprimé] / Lawrence M. CHEN, Auteur ; Marieke S. TOLLENAAR, Auteur ; Shantala A. HARI DASS, Auteur ; Andrée-Anne BOUVETTE-TURCOT, Auteur ; Irina POKHVISNEVA, Auteur ; Helene GAUDREAU, Auteur ; Carine PARENT, Auteur ; Josie DIORIO, Auteur ; Lisa M. MCEWEN, Auteur ; Julia L. MACISAAC, Auteur ; Michael S. KOBOR, Auteur ; Roseriet BEIJERS, Auteur ; Carolina DE WEERTH, Auteur ; Patricia P. SILVEIRA, Auteur ; Sherif KARAMA, Auteur ; Michael J. MEANEY, Auteur ; Kieran J. O'DONNELL, Auteur . - p.1810-1821. Langues : Anglais (eng) in Development and Psychopathology > 32-5 (December 2020) . - p.1810-1821 Mots-clés : *Attention Deficit Disorder with Hyperactivity/genetics  Child  Depression/genetics  Female  Genomics  Humans  Mental Health  Mothers  Pregnancy  *adhd  *child development  *gene by environment (GxE)  *perinatal mental health  *polygenic risk score Index. décimale : PER Périodiques Résumé : Maternal antenatal depression strongly influences child mental health but with considerable inter-individual variation that is, in part, linked to genotype. The challenge is to effectively capture the genotypic influence. We outline a novel approach to describe genomic susceptibility to maternal antenatal depression focusing on child emotional/behavioral difficulties. Two cohorts provided measures of maternal depression, child genetic variation, and child mental health symptoms. We constructed a conventional polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) (PRSADHD) that significantly moderated the association between maternal antenatal depression and internalizing problems at 60 months (p = 2.94 × 10-4, R2 = .18). We then constructed an interaction PRS (xPRS) based on a subset of those single nucleotide polymorphisms from the PRSADHD that most accounted for the moderation of the association between maternal antenatal depression and child outcome. The interaction between maternal antenatal depression and this xPRS accounted for a larger proportion of the variance in child emotional/behavioral problems than models based on any PRSADHD (p = 5.50 × 10-9, R2 = .27), with similar findings in the replication cohort. The xPRS was significantly enriched for genes involved in neuronal development and synaptic function. Our study illustrates a novel approach to the study of genotypic moderation on the impact of maternal antenatal depression on child mental health and highlights the utility of the xPRS approach. These findings advance our understanding of individual differences in the developmental origins of mental health. En ligne : http://dx.doi.org/10.1017/s0954579420001418 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=437

Polygenic differential susceptibility to prenatal adversity / Jay BELSKY in Development and Psychopathology, 31-2 (May 2019)  

Public ISBD [article]  inDevelopment and Psychopathology > 31-2 (May 2019) . - p.439-441 Titre : Polygenic differential susceptibility to prenatal adversity Type de document : texte imprimé Auteurs : Jay BELSKY, Auteur ; Irina POKHVISNEVA, Auteur ; Anu Sathyan Sathyapalan REMA, Auteur ; Birit F.P. BROEKMAN, Auteur ; Michael PLUESS, Auteur ; Kieran J. O'DONNELL, Auteur ; Michael J. MEANEY, Auteur ; Patricia P. SILVEIRA, Auteur Article en page(s) : p.439-441 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : A recent article in this journal reported a number of gene × environment interactions involving a serotonin transporter–gene network polygenic score and a composite index of prenatal adversity predicting several problem behavior outcomes at 48 months (e.g., anxious/depressed, pervasive developmental problems) and at 60 months (e.g., withdrawal, internalizing problems), yet did not illuminate the nature or form these genetic × environment interactions took. Here we report results of six additional analyses to evaluate whether these interactions reflected diathesis–stress or differential–susceptibility related processes. Analyses of the regions of significance and proportion of interaction index are consistent with the diathesis–stress model, seemingly because of the truncated nature of the adversity score (which did not extend to supportive/positive prenatal experiences/exposures); in contrast, the proportion (of cases) affected index favors the differential–susceptibility model. These results suggest the need for future studies to extend measurement of the prenatal environment to highly supportive experiences and exposures. En ligne : http://dx.doi.org/10.1017/S0954579418000378 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=393 [article] Polygenic differential susceptibility to prenatal adversity [texte imprimé] / Jay BELSKY, Auteur ; Irina POKHVISNEVA, Auteur ; Anu Sathyan Sathyapalan REMA, Auteur ; Birit F.P. BROEKMAN, Auteur ; Michael PLUESS, Auteur ; Kieran J. O'DONNELL, Auteur ; Michael J. MEANEY, Auteur ; Patricia P. SILVEIRA, Auteur . - p.439-441. Langues : Anglais (eng) in Development and Psychopathology > 31-2 (May 2019) . - p.439-441 Index. décimale : PER Périodiques Résumé : A recent article in this journal reported a number of gene × environment interactions involving a serotonin transporter–gene network polygenic score and a composite index of prenatal adversity predicting several problem behavior outcomes at 48 months (e.g., anxious/depressed, pervasive developmental problems) and at 60 months (e.g., withdrawal, internalizing problems), yet did not illuminate the nature or form these genetic × environment interactions took. Here we report results of six additional analyses to evaluate whether these interactions reflected diathesis–stress or differential–susceptibility related processes. Analyses of the regions of significance and proportion of interaction index are consistent with the diathesis–stress model, seemingly because of the truncated nature of the adversity score (which did not extend to supportive/positive prenatal experiences/exposures); in contrast, the proportion (of cases) affected index favors the differential–susceptibility model. These results suggest the need for future studies to extend measurement of the prenatal environment to highly supportive experiences and exposures. En ligne : http://dx.doi.org/10.1017/S0954579418000378 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=393

The association between temperament and polygenic score for psychopathology from infancy to middle childhood / Eloise FREITAG in Journal of Child Psychology and Psychiatry, 66-8 (August 2025)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 66-8 (August 2025) . - p.1155-1169 Titre : The association between temperament and polygenic score for psychopathology from infancy to middle childhood Type de document : texte imprimé Auteurs : Eloise FREITAG, Auteur ; Caroline M. KELSEY, Auteur ; Euclides José DE MENDONÇA FILHO, Auteur ; Irina POKHVISNEVA, Auteur ; Sachin PATEL, Auteur ; Patricia Pelufo SILVEIRA, Auteur ; Michelle BOSQUET ENLOW, Auteur ; Charles A. NELSON, Auteur Article en page(s) : p.1155-1169 Langues : Anglais (eng) Mots-clés : ADHD  anxiety  childhood  infancy  polygenic scores  temperament Index. décimale : PER Périodiques Résumé : Background Certain temperament characteristics, such as low effortful control and high negative affectivity, are linked to an elevated likelihood for later psychopathology. Although genetic vulnerability has been associated with a number of psychiatric conditions, little work has examined the genetic architecture underlying temperament or the genetic overlap between early temperament profiles and later mental health outcomes. The present study examined associations of polygenic scores for anxiety (PGS-Anxiety) and ADHD (PGS-ADHD) with temperament characteristics in a longitudinal sample of children assessed from infancy through age 7 years. Methods Analyses were conducted in a sample of children (European Ancestry n 476; Full Sample [European and other ancestries] N 606). Results We observed an age-by-PGS interaction on effortful control. As children aged, there appeared to be stronger negative associations between PGS-ADHD and effortful control. No associations were observed between PGS-Anxiety and negative affectivity. Conclusions Overall, the findings suggest some support for associations between genetic underpinnings for externalizing psychopathology and temperament that increase over time. En ligne : https://doi.org/10.1111/jcpp.14140 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=565 [article] The association between temperament and polygenic score for psychopathology from infancy to middle childhood [texte imprimé] / Eloise FREITAG, Auteur ; Caroline M. KELSEY, Auteur ; Euclides José DE MENDONÇA FILHO, Auteur ; Irina POKHVISNEVA, Auteur ; Sachin PATEL, Auteur ; Patricia Pelufo SILVEIRA, Auteur ; Michelle BOSQUET ENLOW, Auteur ; Charles A. NELSON, Auteur . - p.1155-1169. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 66-8 (August 2025) . - p.1155-1169 Mots-clés : ADHD  anxiety  childhood  infancy  polygenic scores  temperament Index. décimale : PER Périodiques Résumé : Background Certain temperament characteristics, such as low effortful control and high negative affectivity, are linked to an elevated likelihood for later psychopathology. Although genetic vulnerability has been associated with a number of psychiatric conditions, little work has examined the genetic architecture underlying temperament or the genetic overlap between early temperament profiles and later mental health outcomes. The present study examined associations of polygenic scores for anxiety (PGS-Anxiety) and ADHD (PGS-ADHD) with temperament characteristics in a longitudinal sample of children assessed from infancy through age 7 years. Methods Analyses were conducted in a sample of children (European Ancestry n 476; Full Sample [European and other ancestries] N 606). Results We observed an age-by-PGS interaction on effortful control. As children aged, there appeared to be stronger negative associations between PGS-ADHD and effortful control. No associations were observed between PGS-Anxiety and negative affectivity. Conclusions Overall, the findings suggest some support for associations between genetic underpinnings for externalizing psychopathology and temperament that increase over time. En ligne : https://doi.org/10.1111/jcpp.14140 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=565

The early care environment and DNA methylome variation in childhood / Elika GARG in Development and Psychopathology, 30-3 (August 2018)  

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