Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study

Abstract 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 i...
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Autor*in:	Axel Krug [verfasserIn] Markus Wöhr [verfasserIn] Dominik Seffer [verfasserIn] Henrike Rippberger [verfasserIn] A. Özge Sungur [verfasserIn] Bruno Dietsche [verfasserIn] Frederike Stein [verfasserIn] Sugirthan Sivalingam [verfasserIn] Andreas J. Forstner [verfasserIn] Stephanie H. Witt [verfasserIn] Helene Dukal [verfasserIn] Fabian Streit [verfasserIn] Anna Maaser [verfasserIn] Stefanie Heilmann-Heimbach [verfasserIn] Till F. M. Andlauer [verfasserIn] Stefan Herms [verfasserIn] Per Hoffmann [verfasserIn] Marcella Rietschel [verfasserIn] Markus M. Nöthen [verfasserIn] Martin Lackinger [verfasserIn] Gerhard Schratt [verfasserIn] Michael Koch [verfasserIn] Rainer K. W. Schwarting [verfasserIn] Tilo Kircher [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	Advanced paternal age (APA) Diffusion tension imaging (DTI) Voxel-based morphometry (VBM) Social behavior Ultrasonic vocalization

Übergeordnetes Werk:	In: Molecular Autism - BMC, 2010, 11(2020), 1, Seite 19
Übergeordnetes Werk:	volume:11 ; year:2020 ; number:1 ; pages:19

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s13229-020-00345-2

Katalog-ID:	DOAJ068662416

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520			\|a Abstract 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.
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allfields	10.1186/s13229-020-00345-2 doi (DE-627)DOAJ068662416 (DE-599)DOAJ06f7773622724f6e8c4366eee4a1e2fc DE-627 ger DE-627 rakwb eng RC346-429 Axel Krug verfasserin aut Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Advanced paternal age (APA) Diffusion tension imaging (DTI) Voxel-based morphometry (VBM) Social behavior Ultrasonic vocalization Neurology. Diseases of the nervous system Markus Wöhr verfasserin aut Dominik Seffer verfasserin aut Henrike Rippberger verfasserin aut A. Özge Sungur verfasserin aut Bruno Dietsche verfasserin aut Frederike Stein verfasserin aut Sugirthan Sivalingam verfasserin aut Andreas J. Forstner verfasserin aut Stephanie H. Witt verfasserin aut Helene Dukal verfasserin aut Fabian Streit verfasserin aut Anna Maaser verfasserin aut Stefanie Heilmann-Heimbach verfasserin aut Till F. M. Andlauer verfasserin aut Stefan Herms verfasserin aut Per Hoffmann verfasserin aut Marcella Rietschel verfasserin aut Markus M. Nöthen verfasserin aut Martin Lackinger verfasserin aut Gerhard Schratt verfasserin aut Michael Koch verfasserin aut Rainer K. W. Schwarting verfasserin aut Tilo Kircher verfasserin aut In Molecular Autism BMC, 2010 11(2020), 1, Seite 19 (DE-627)620141522 (DE-600)2540930-X 20402392 nnns volume:11 year:2020 number:1 pages:19 https://doi.org/10.1186/s13229-020-00345-2 kostenfrei https://doaj.org/article/06f7773622724f6e8c4366eee4a1e2fc kostenfrei http://link.springer.com/article/10.1186/s13229-020-00345-2 kostenfrei https://doaj.org/toc/2040-2392 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 1 19
spelling	10.1186/s13229-020-00345-2 doi (DE-627)DOAJ068662416 (DE-599)DOAJ06f7773622724f6e8c4366eee4a1e2fc DE-627 ger DE-627 rakwb eng RC346-429 Axel Krug verfasserin aut Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Advanced paternal age (APA) Diffusion tension imaging (DTI) Voxel-based morphometry (VBM) Social behavior Ultrasonic vocalization Neurology. Diseases of the nervous system Markus Wöhr verfasserin aut Dominik Seffer verfasserin aut Henrike Rippberger verfasserin aut A. Özge Sungur verfasserin aut Bruno Dietsche verfasserin aut Frederike Stein verfasserin aut Sugirthan Sivalingam verfasserin aut Andreas J. Forstner verfasserin aut Stephanie H. Witt verfasserin aut Helene Dukal verfasserin aut Fabian Streit verfasserin aut Anna Maaser verfasserin aut Stefanie Heilmann-Heimbach verfasserin aut Till F. M. Andlauer verfasserin aut Stefan Herms verfasserin aut Per Hoffmann verfasserin aut Marcella Rietschel verfasserin aut Markus M. Nöthen verfasserin aut Martin Lackinger verfasserin aut Gerhard Schratt verfasserin aut Michael Koch verfasserin aut Rainer K. W. Schwarting verfasserin aut Tilo Kircher verfasserin aut In Molecular Autism BMC, 2010 11(2020), 1, Seite 19 (DE-627)620141522 (DE-600)2540930-X 20402392 nnns volume:11 year:2020 number:1 pages:19 https://doi.org/10.1186/s13229-020-00345-2 kostenfrei https://doaj.org/article/06f7773622724f6e8c4366eee4a1e2fc kostenfrei http://link.springer.com/article/10.1186/s13229-020-00345-2 kostenfrei https://doaj.org/toc/2040-2392 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 1 19
allfields_unstemmed	10.1186/s13229-020-00345-2 doi (DE-627)DOAJ068662416 (DE-599)DOAJ06f7773622724f6e8c4366eee4a1e2fc DE-627 ger DE-627 rakwb eng RC346-429 Axel Krug verfasserin aut Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Advanced paternal age (APA) Diffusion tension imaging (DTI) Voxel-based morphometry (VBM) Social behavior Ultrasonic vocalization Neurology. Diseases of the nervous system Markus Wöhr verfasserin aut Dominik Seffer verfasserin aut Henrike Rippberger verfasserin aut A. Özge Sungur verfasserin aut Bruno Dietsche verfasserin aut Frederike Stein verfasserin aut Sugirthan Sivalingam verfasserin aut Andreas J. Forstner verfasserin aut Stephanie H. Witt verfasserin aut Helene Dukal verfasserin aut Fabian Streit verfasserin aut Anna Maaser verfasserin aut Stefanie Heilmann-Heimbach verfasserin aut Till F. M. Andlauer verfasserin aut Stefan Herms verfasserin aut Per Hoffmann verfasserin aut Marcella Rietschel verfasserin aut Markus M. Nöthen verfasserin aut Martin Lackinger verfasserin aut Gerhard Schratt verfasserin aut Michael Koch verfasserin aut Rainer K. W. Schwarting verfasserin aut Tilo Kircher verfasserin aut In Molecular Autism BMC, 2010 11(2020), 1, Seite 19 (DE-627)620141522 (DE-600)2540930-X 20402392 nnns volume:11 year:2020 number:1 pages:19 https://doi.org/10.1186/s13229-020-00345-2 kostenfrei https://doaj.org/article/06f7773622724f6e8c4366eee4a1e2fc kostenfrei http://link.springer.com/article/10.1186/s13229-020-00345-2 kostenfrei https://doaj.org/toc/2040-2392 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 1 19
allfieldsGer	10.1186/s13229-020-00345-2 doi (DE-627)DOAJ068662416 (DE-599)DOAJ06f7773622724f6e8c4366eee4a1e2fc DE-627 ger DE-627 rakwb eng RC346-429 Axel Krug verfasserin aut Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Advanced paternal age (APA) Diffusion tension imaging (DTI) Voxel-based morphometry (VBM) Social behavior Ultrasonic vocalization Neurology. Diseases of the nervous system Markus Wöhr verfasserin aut Dominik Seffer verfasserin aut Henrike Rippberger verfasserin aut A. Özge Sungur verfasserin aut Bruno Dietsche verfasserin aut Frederike Stein verfasserin aut Sugirthan Sivalingam verfasserin aut Andreas J. Forstner verfasserin aut Stephanie H. Witt verfasserin aut Helene Dukal verfasserin aut Fabian Streit verfasserin aut Anna Maaser verfasserin aut Stefanie Heilmann-Heimbach verfasserin aut Till F. M. Andlauer verfasserin aut Stefan Herms verfasserin aut Per Hoffmann verfasserin aut Marcella Rietschel verfasserin aut Markus M. Nöthen verfasserin aut Martin Lackinger verfasserin aut Gerhard Schratt verfasserin aut Michael Koch verfasserin aut Rainer K. W. Schwarting verfasserin aut Tilo Kircher verfasserin aut In Molecular Autism BMC, 2010 11(2020), 1, Seite 19 (DE-627)620141522 (DE-600)2540930-X 20402392 nnns volume:11 year:2020 number:1 pages:19 https://doi.org/10.1186/s13229-020-00345-2 kostenfrei https://doaj.org/article/06f7773622724f6e8c4366eee4a1e2fc kostenfrei http://link.springer.com/article/10.1186/s13229-020-00345-2 kostenfrei https://doaj.org/toc/2040-2392 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 1 19
allfieldsSound	10.1186/s13229-020-00345-2 doi (DE-627)DOAJ068662416 (DE-599)DOAJ06f7773622724f6e8c4366eee4a1e2fc DE-627 ger DE-627 rakwb eng RC346-429 Axel Krug verfasserin aut Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Advanced paternal age (APA) Diffusion tension imaging (DTI) Voxel-based morphometry (VBM) Social behavior Ultrasonic vocalization Neurology. Diseases of the nervous system Markus Wöhr verfasserin aut Dominik Seffer verfasserin aut Henrike Rippberger verfasserin aut A. Özge Sungur verfasserin aut Bruno Dietsche verfasserin aut Frederike Stein verfasserin aut Sugirthan Sivalingam verfasserin aut Andreas J. Forstner verfasserin aut Stephanie H. Witt verfasserin aut Helene Dukal verfasserin aut Fabian Streit verfasserin aut Anna Maaser verfasserin aut Stefanie Heilmann-Heimbach verfasserin aut Till F. M. Andlauer verfasserin aut Stefan Herms verfasserin aut Per Hoffmann verfasserin aut Marcella Rietschel verfasserin aut Markus M. Nöthen verfasserin aut Martin Lackinger verfasserin aut Gerhard Schratt verfasserin aut Michael Koch verfasserin aut Rainer K. W. Schwarting verfasserin aut Tilo Kircher verfasserin aut In Molecular Autism BMC, 2010 11(2020), 1, Seite 19 (DE-627)620141522 (DE-600)2540930-X 20402392 nnns volume:11 year:2020 number:1 pages:19 https://doi.org/10.1186/s13229-020-00345-2 kostenfrei https://doaj.org/article/06f7773622724f6e8c4366eee4a1e2fc kostenfrei http://link.springer.com/article/10.1186/s13229-020-00345-2 kostenfrei https://doaj.org/toc/2040-2392 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 1 19
language	English
source	In Molecular Autism 11(2020), 1, Seite 19 volume:11 year:2020 number:1 pages:19
sourceStr	In Molecular Autism 11(2020), 1, Seite 19 volume:11 year:2020 number:1 pages:19
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Advanced paternal age (APA) Diffusion tension imaging (DTI) Voxel-based morphometry (VBM) Social behavior Ultrasonic vocalization Neurology. Diseases of the nervous system
isfreeaccess_bool	true
container_title	Molecular Autism
authorswithroles_txt_mv	Axel Krug @@aut@@ Markus Wöhr @@aut@@ Dominik Seffer @@aut@@ Henrike Rippberger @@aut@@ A. Özge Sungur @@aut@@ Bruno Dietsche @@aut@@ Frederike Stein @@aut@@ Sugirthan Sivalingam @@aut@@ Andreas J. Forstner @@aut@@ Stephanie H. Witt @@aut@@ Helene Dukal @@aut@@ Fabian Streit @@aut@@ Anna Maaser @@aut@@ Stefanie Heilmann-Heimbach @@aut@@ Till F. M. Andlauer @@aut@@ Stefan Herms @@aut@@ Per Hoffmann @@aut@@ Marcella Rietschel @@aut@@ Markus M. Nöthen @@aut@@ Martin Lackinger @@aut@@ Gerhard Schratt @@aut@@ Michael Koch @@aut@@ Rainer K. W. Schwarting @@aut@@ Tilo Kircher @@aut@@
publishDateDaySort_date	2020-01-01T00:00:00Z
hierarchy_top_id	620141522
id	DOAJ068662416
language_de	englisch
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callnumber-first	R - Medicine
author	Axel Krug
spellingShingle	Axel Krug misc RC346-429 misc Advanced paternal age (APA) misc Diffusion tension imaging (DTI) misc Voxel-based morphometry (VBM) misc Social behavior misc Ultrasonic vocalization misc Neurology. Diseases of the nervous system Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study
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topic_title	RC346-429 Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study Advanced paternal age (APA) Diffusion tension imaging (DTI) Voxel-based morphometry (VBM) Social behavior Ultrasonic vocalization
topic	misc RC346-429 misc Advanced paternal age (APA) misc Diffusion tension imaging (DTI) misc Voxel-based morphometry (VBM) misc Social behavior misc Ultrasonic vocalization misc Neurology. Diseases of the nervous system
topic_unstemmed	misc RC346-429 misc Advanced paternal age (APA) misc Diffusion tension imaging (DTI) misc Voxel-based morphometry (VBM) misc Social behavior misc Ultrasonic vocalization misc Neurology. Diseases of the nervous system
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title	Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study
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title_full	Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study
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author_browse	Axel Krug Markus Wöhr Dominik Seffer Henrike Rippberger A. Özge Sungur Bruno Dietsche Frederike Stein Sugirthan Sivalingam Andreas J. Forstner Stephanie H. Witt Helene Dukal Fabian Streit Anna Maaser Stefanie Heilmann-Heimbach Till F. M. Andlauer Stefan Herms Per Hoffmann Marcella Rietschel Markus M. Nöthen Martin Lackinger Gerhard Schratt Michael Koch Rainer K. W. Schwarting Tilo Kircher
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title_sort	advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study
callnumber	RC346-429
title_auth	Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study
abstract	Abstract 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.
abstractGer	Abstract 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.
abstract_unstemmed	Abstract 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.
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title_short	Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study
url	https://doi.org/10.1186/s13229-020-00345-2 https://doaj.org/article/06f7773622724f6e8c4366eee4a1e2fc http://link.springer.com/article/10.1186/s13229-020-00345-2 https://doaj.org/toc/2040-2392
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author2	Markus Wöhr Dominik Seffer Henrike Rippberger A. Özge Sungur Bruno Dietsche Frederike Stein Sugirthan Sivalingam Andreas J. Forstner Stephanie H. Witt Helene Dukal Fabian Streit Anna Maaser Stefanie Heilmann-Heimbach Till F. M. Andlauer Stefan Herms Per Hoffmann Marcella Rietschel Markus M. Nöthen Martin Lackinger Gerhard Schratt Michael Koch Rainer K. W. Schwarting Tilo Kircher
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