Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study / Axel KRUG in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) . - 54 p. Titre : Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study Type de document : Texte imprimé et/ou numérique Auteurs : Axel KRUG, Auteur ; Markus WÖHR, Auteur ; Dominik SEFFER, Auteur ; Henrike RIPPBERGER, Auteur ; A. Özge SUNGUR, Auteur ; Bruno DIETSCHE, Auteur ; Frederike STEIN, Auteur ; Sugirthan SIVALINGAM, Auteur ; Andreas J. FORSTNER, Auteur ; Stephanie H. WITT, Auteur ; Helene DUKAL, Auteur ; Fabian STREIT, Auteur ; Anna MAASER, Auteur ; Stefanie HEILMANN-HEIMBACH, Auteur ; Till F. M. ANDLAUER, Auteur ; Stefan HERMS, Auteur ; Per HOFFMANN, Auteur ; Marcella RIETSCHEL, Auteur ; Markus M. NÖTHEN, Auteur ; Martin LACKINGER, Auteur ; Gerhard SCHRATT, Auteur ; Michael KOCH, Auteur ; Rainer K. W. SCHWARTING, Auteur ; Tilo KIRCHER, Auteur Article en page(s) : 54 p. Langues : Anglais (eng) Mots-clés : Advanced paternal age (APA)  Diffusion tension imaging (DTI)  Social behavior  Ultrasonic vocalization  Voxel-based morphometry (VBM) Index. décimale : PER Périodiques Résumé : Advanced paternal age (APA) is a risk factor for several neurodevelopmental disorders, including autism and schizophrenia. The potential mechanisms conferring this risk are poorly understood. Here, we show that the personality traits schizotypy and neuroticism correlated with paternal age in healthy subjects (N = 677). Paternal age was further positively associated with gray matter volume (VBM, N = 342) in the right prefrontal and the right medial temporal cortex. The integrity of fiber tracts (DTI, N = 222) connecting these two areas correlated positively with paternal age. Genome-wide methylation analysis in humans showed differential methylation in APA individuals, linking APA to epigenetic mechanisms. A corresponding phenotype was obtained in our rat model. APA rats displayed social-communication deficits and emitted fewer pro-social ultrasonic vocalizations compared to controls. They further showed repetitive and stereotyped patterns of behavior, together with higher anxiety during early development. At the neurobiological level, microRNAs miR-132 and miR-134 were both differentially regulated in rats and humans depending on APA. This study demonstrates associations between APA and social behaviors across species. They might be driven by changes in the expression of microRNAs and/or epigenetic changes regulating neuronal plasticity, leading to brain morphological changes and fronto-hippocampal connectivity, a network which has been implicated in social interaction. En ligne : http://dx.doi.org/10.1186/s13229-020-00345-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427 [article] Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study [Texte imprimé et/ou numérique] / Axel KRUG, Auteur ; Markus WÖHR, Auteur ; Dominik SEFFER, Auteur ; Henrike RIPPBERGER, Auteur ; A. Özge SUNGUR, Auteur ; Bruno DIETSCHE, Auteur ; Frederike STEIN, Auteur ; Sugirthan SIVALINGAM, Auteur ; Andreas J. FORSTNER, Auteur ; Stephanie H. WITT, Auteur ; Helene DUKAL, Auteur ; Fabian STREIT, Auteur ; Anna MAASER, Auteur ; Stefanie HEILMANN-HEIMBACH, Auteur ; Till F. M. ANDLAUER, Auteur ; Stefan HERMS, Auteur ; Per HOFFMANN, Auteur ; Marcella RIETSCHEL, Auteur ; Markus M. NÖTHEN, Auteur ; Martin LACKINGER, Auteur ; Gerhard SCHRATT, Auteur ; Michael KOCH, Auteur ; Rainer K. W. SCHWARTING, Auteur ; Tilo KIRCHER, Auteur . - 54 p. Langues : Anglais (eng) in Molecular Autism > 11 (2020) . - 54 p. Mots-clés : Advanced paternal age (APA)  Diffusion tension imaging (DTI)  Social behavior  Ultrasonic vocalization  Voxel-based morphometry (VBM) Index. décimale : PER Périodiques Résumé : Advanced paternal age (APA) is a risk factor for several neurodevelopmental disorders, including autism and schizophrenia. The potential mechanisms conferring this risk are poorly understood. Here, we show that the personality traits schizotypy and neuroticism correlated with paternal age in healthy subjects (N = 677). Paternal age was further positively associated with gray matter volume (VBM, N = 342) in the right prefrontal and the right medial temporal cortex. The integrity of fiber tracts (DTI, N = 222) connecting these two areas correlated positively with paternal age. Genome-wide methylation analysis in humans showed differential methylation in APA individuals, linking APA to epigenetic mechanisms. A corresponding phenotype was obtained in our rat model. APA rats displayed social-communication deficits and emitted fewer pro-social ultrasonic vocalizations compared to controls. They further showed repetitive and stereotyped patterns of behavior, together with higher anxiety during early development. At the neurobiological level, microRNAs miR-132 and miR-134 were both differentially regulated in rats and humans depending on APA. This study demonstrates associations between APA and social behaviors across species. They might be driven by changes in the expression of microRNAs and/or epigenetic changes regulating neuronal plasticity, leading to brain morphological changes and fronto-hippocampal connectivity, a network which has been implicated in social interaction. En ligne : http://dx.doi.org/10.1186/s13229-020-00345-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427

Polygenic risk score and peer victimisation independently predict depressive symptoms in adolescence: results from the Quebec Longitudinal Study of Children Development / Léa C. PERRET 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.388-396 Titre : Polygenic risk score and peer victimisation independently predict depressive symptoms in adolescence: results from the Quebec Longitudinal Study of Children Development Type de document : Texte imprimé et/ou numérique Auteurs : Léa C. PERRET, Auteur ; Michel BOIVIN, Auteur ; Geneviève MORNEAU-VAILLANCOURT, Auteur ; Till F. M. ANDLAUER, Auteur ; Stéphane PAQUIN, Auteur ; Stéphanie LANGEVIN, Auteur ; Alain GIRARD, Auteur ; Gustavo TURECKI, Auteur ; Kieran J. O'DONNELL, Auteur ; Richard E. TREMBLAY, Auteur ; Sylvana M. CÔTÉ, Auteur ; Jean-Philippe GOUIN, Auteur ; Isabelle OUELLET-MORIN, Auteur ; Marie-Claude GEOFFROY, Auteur Article en page(s) : p.388-396 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background Peer victimisation has been associated with depressive symptoms during adolescence, however not all peer victimised adolescents will exhibit such symptoms. This study tested whether having a genetic predisposition to developing depression increased the risk of experiencing depressive symptoms in peer victimised youth. To date, no study has explored such gene-environment interaction using a polygenic risk score for depression (PRS-depression) in the context of peer victimisation and depressive symptoms in adolescence. Methods The sample included 748 participants born in 1997/98 from the Quebec Longitudinal Study of Child Development with genotype data and prospectively collected information on peer victimisation (12-13 years) obtained from both self- and teacher-reports, as well as self-reported depressive symptoms (15-17 years). The PRS-depression was based on the genome-wide association meta-analysis of broad depression by Howard et al. (2019). Results Self- and teacher-reported peer victimisation in early adolescence were both associated with depressive symptoms in adolescence (Î2=0.34, p < .001; Î2=0.14, p=.001 respectively), and this association remained significant when accounting for PRS-depression (Î2=0.33, p < .001; Î2=0.13, p=.002 respectively). PRS-depression was independently associated with depressive symptoms, but there was no significant PRS-depression by peer victimisation interaction (self-reported and teacher-reported). PRS-depression was correlated with self-reported, but not teacher-reported, peer victimisation. Conclusions Our findings suggested that a partial measure of an individual's genetic predisposition to depression, as measured by PRS-depression, and being exposed to peer victimisation (self- and teacher-reported) were independently associated with depressive symptoms in adolescence. Furthermore, PRS-depression did not exacerbate the risk of depressive symptoms among adolescents who had been peer victimised. Lastly, we found evidence of a gene-environment correlation between PRS-depression and self-reported peer victimisation. Future studies are needed to replicate this finding and to further understand the role of genetic predispositions in experiencing depressive symptoms following peer victimisation. En ligne : https://doi.org/10.1111/jcpp.13706 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=493 [article] Polygenic risk score and peer victimisation independently predict depressive symptoms in adolescence: results from the Quebec Longitudinal Study of Children Development [Texte imprimé et/ou numérique] / Léa C. PERRET, Auteur ; Michel BOIVIN, Auteur ; Geneviève MORNEAU-VAILLANCOURT, Auteur ; Till F. M. ANDLAUER, Auteur ; Stéphane PAQUIN, Auteur ; Stéphanie LANGEVIN, Auteur ; Alain GIRARD, Auteur ; Gustavo TURECKI, Auteur ; Kieran J. O'DONNELL, Auteur ; Richard E. TREMBLAY, Auteur ; Sylvana M. CÔTÉ, Auteur ; Jean-Philippe GOUIN, Auteur ; Isabelle OUELLET-MORIN, Auteur ; Marie-Claude GEOFFROY, Auteur . - p.388-396. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 64-3 (March 2023) . - p.388-396 Index. décimale : PER Périodiques Résumé : Background Peer victimisation has been associated with depressive symptoms during adolescence, however not all peer victimised adolescents will exhibit such symptoms. This study tested whether having a genetic predisposition to developing depression increased the risk of experiencing depressive symptoms in peer victimised youth. To date, no study has explored such gene-environment interaction using a polygenic risk score for depression (PRS-depression) in the context of peer victimisation and depressive symptoms in adolescence. Methods The sample included 748 participants born in 1997/98 from the Quebec Longitudinal Study of Child Development with genotype data and prospectively collected information on peer victimisation (12-13 years) obtained from both self- and teacher-reports, as well as self-reported depressive symptoms (15-17 years). The PRS-depression was based on the genome-wide association meta-analysis of broad depression by Howard et al. (2019). Results Self- and teacher-reported peer victimisation in early adolescence were both associated with depressive symptoms in adolescence (Î2=0.34, p < .001; Î2=0.14, p=.001 respectively), and this association remained significant when accounting for PRS-depression (Î2=0.33, p < .001; Î2=0.13, p=.002 respectively). PRS-depression was independently associated with depressive symptoms, but there was no significant PRS-depression by peer victimisation interaction (self-reported and teacher-reported). PRS-depression was correlated with self-reported, but not teacher-reported, peer victimisation. Conclusions Our findings suggested that a partial measure of an individual's genetic predisposition to depression, as measured by PRS-depression, and being exposed to peer victimisation (self- and teacher-reported) were independently associated with depressive symptoms in adolescence. Furthermore, PRS-depression did not exacerbate the risk of depressive symptoms among adolescents who had been peer victimised. Lastly, we found evidence of a gene-environment correlation between PRS-depression and self-reported peer victimisation. Future studies are needed to replicate this finding and to further understand the role of genetic predispositions in experiencing depressive symptoms following peer victimisation. En ligne : https://doi.org/10.1111/jcpp.13706 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=493

Polygenic scores differentially predict developmental trajectories of subtypes of social withdrawal in childhood / Geneviève MORNEAU-VAILLANCOURT in Journal of Child Psychology and Psychiatry, 62-11 (November 2021)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 62-11 (November 2021) . - p.1320-1329 Titre : Polygenic scores differentially predict developmental trajectories of subtypes of social withdrawal in childhood Type de document : Texte imprimé et/ou numérique Auteurs : Geneviève MORNEAU-VAILLANCOURT, Auteur ; Till F. M. ANDLAUER, Auteur ; I. OUELLET-MORIN, Auteur ; S. PAQUIN, Auteur ; M. R. BRENDGEN, Auteur ; F. VITARO, Auteur ; Jean-Philippe GOUIN, Auteur ; Jean R. SEGUIN, Auteur ; É GAGNON, Auteur ; Rosa CHEESMAN, Auteur ; N. FORGET-DUBOIS, Auteur ; G. A. ROULEAU, Auteur ; G. TURECKI, Auteur ; R. E. TREMBLAY, Auteur ; Sylvana M. CÔTÉ, Auteur ; G. DIONNE, Auteur ; Michel BOIVIN, Auteur Article en page(s) : p.1320-1329 Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity  Autism Spectrum Disorder  Child  Humans  Infant, Newborn  Loneliness  Longitudinal Studies  Multifactorial Inheritance/genetics  Prospective Studies  Social withdrawal  polygenic scores  preference for solitude  social wariness  trajectories Index. décimale : PER Périodiques Résumé : BACKGROUND: Children who consistently withdraw from social situations face increased risk for later socioemotional difficulties. Twin studies indicate that genetic factors substantially account for the persistence of social withdrawal over time. However, the molecular genetic etiology of chronic courses of social wariness and preference for solitude, two dimensions of social withdrawal, remains undocumented. The objectives of the present study were (a) to identify high-risk trajectories for social wariness and preference for solitude in childhood and (b) to examine whether falling on these high-risk trajectories can be predicted by specific polygenic scores for mental health traits and disorders and by a general polygenic predisposition to these traits. METHODS: Teachers evaluated 971 genotyped children at five occasions (age 6 to 12 years) from two prospective longitudinal studies, the Quebec Newborn Twin Study and the Quebec Longitudinal Study of Child Development. Developmental trajectories for social wariness and preference for solitude were identified. We tested whether polygenic scores for attention deficit hyperactivity disorder, autism spectrum disorder, depression, loneliness, and subjective well-being, as well as a general mental health genetic risk score derived across these traits, were associated with the developmental trajectories. RESULTS: Polygenic scores differentially predicted social wariness and preference for solitude. Only the loneliness polygenic score significantly predicted the high trajectory for social wariness. By contrast, the general mental health genetic risk score factor was associated with the trajectory depicting high-chronic preference for solitude. CONCLUSIONS: Distinct associations were uncovered between the polygenic scores, social wariness, and preference for solitude. En ligne : http://dx.doi.org/10.1111/jcpp.13459 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=456 [article] Polygenic scores differentially predict developmental trajectories of subtypes of social withdrawal in childhood [Texte imprimé et/ou numérique] / Geneviève MORNEAU-VAILLANCOURT, Auteur ; Till F. M. ANDLAUER, Auteur ; I. OUELLET-MORIN, Auteur ; S. PAQUIN, Auteur ; M. R. BRENDGEN, Auteur ; F. VITARO, Auteur ; Jean-Philippe GOUIN, Auteur ; Jean R. SEGUIN, Auteur ; É GAGNON, Auteur ; Rosa CHEESMAN, Auteur ; N. FORGET-DUBOIS, Auteur ; G. A. ROULEAU, Auteur ; G. TURECKI, Auteur ; R. E. TREMBLAY, Auteur ; Sylvana M. CÔTÉ, Auteur ; G. DIONNE, Auteur ; Michel BOIVIN, Auteur . - p.1320-1329. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 62-11 (November 2021) . - p.1320-1329 Mots-clés : Attention Deficit Disorder with Hyperactivity  Autism Spectrum Disorder  Child  Humans  Infant, Newborn  Loneliness  Longitudinal Studies  Multifactorial Inheritance/genetics  Prospective Studies  Social withdrawal  polygenic scores  preference for solitude  social wariness  trajectories Index. décimale : PER Périodiques Résumé : BACKGROUND: Children who consistently withdraw from social situations face increased risk for later socioemotional difficulties. Twin studies indicate that genetic factors substantially account for the persistence of social withdrawal over time. However, the molecular genetic etiology of chronic courses of social wariness and preference for solitude, two dimensions of social withdrawal, remains undocumented. The objectives of the present study were (a) to identify high-risk trajectories for social wariness and preference for solitude in childhood and (b) to examine whether falling on these high-risk trajectories can be predicted by specific polygenic scores for mental health traits and disorders and by a general polygenic predisposition to these traits. METHODS: Teachers evaluated 971 genotyped children at five occasions (age 6 to 12 years) from two prospective longitudinal studies, the Quebec Newborn Twin Study and the Quebec Longitudinal Study of Child Development. Developmental trajectories for social wariness and preference for solitude were identified. We tested whether polygenic scores for attention deficit hyperactivity disorder, autism spectrum disorder, depression, loneliness, and subjective well-being, as well as a general mental health genetic risk score derived across these traits, were associated with the developmental trajectories. RESULTS: Polygenic scores differentially predicted social wariness and preference for solitude. Only the loneliness polygenic score significantly predicted the high trajectory for social wariness. By contrast, the general mental health genetic risk score factor was associated with the trajectory depicting high-chronic preference for solitude. CONCLUSIONS: Distinct associations were uncovered between the polygenic scores, social wariness, and preference for solitude. En ligne : http://dx.doi.org/10.1111/jcpp.13459 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=456

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