Genetic counseling as preventive intervention: toward individual specification of transgenerational autism risk / Natasha MARRUS in Journal of Neurodevelopmental Disorders, 13 (2021)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 13 (2021) Titre : Genetic counseling as preventive intervention: toward individual specification of transgenerational autism risk Type de document : texte imprimé Auteurs : Natasha MARRUS, Auteur ; Tychele N. TURNER, Auteur ; Elizabeth FORSEN, Auteur ; Drew BOLSTER, Auteur ; Alison MARVIN, Auteur ; Andrew WHITEHOUSE, Auteur ; Laura KLINGER, Auteur ; Christina A. GURNETT, Auteur ; J.N. CONSTANTINO, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/epidemiology/genetics  Autistic Disorder/epidemiology/genetics  Genetic Counseling  Humans  Parents  Prospective Studies  Early detection  Family studies  Personalized medicine  Reproductive health planning  for the Social Responsiveness Scale. Index. décimale : PER Périodiques Résumé : BACKGROUND: Although autism spectrum disorders (ASD) are among the most heritable of all neuropsychiatric syndromes, most affected children are born to unaffected parents. Recently, we reported an average increase of 3-5% over general population risk of ASD among offspring of adults who have first-degree relatives with ASD in a large epidemiologic family sample. A next essential step is to investigate whether there are measurable characteristics of individual parents placing them at higher or lower recurrence risk, as this information could allow more personalized genetic counseling. METHODS: We assembled what is to our knowledge the largest collection of data on the ability of four measurable characteristics of unaffected prospective parents to specify risk for autism among their offspring: (1) sub clinical autistic trait burden, (2) parental history of a sibling with ASD, (3) transmitted autosomal molecular genetic abnormalities, and (4) parental age. Leveraging phenotypic and genetic data in curated family cohorts, we evaluate the respective associations between these factors and child outcome when autism is present in the family in the parental generation. RESULTS: All four characteristics were associated with elevation in offspring risk; however, the magnitude of their predictive power-with the exception of isolated rare inherited pathogenic variants -does not yet reach a threshold that would typically be considered actionable for reproductive decision-making. CONCLUSIONS: Individual specification of risk to offspring of adults in ASD-affected families is not straightforwardly improved by ascertainment of parental phenotype, and it is not yet clear whether genomic screening of prospective parents in families affected by idiopathic ASD is warranted as a clinical standard. Systematic screening of affected family members for heritable pathogenic variants, including rare sex-linked mutations, will identify a subset of families with substantially elevated transmission risk. Polygenic risk scores are only weakly predictive at this time but steadily improving and ultimately may enable more robust prediction either singly or when combined with the risk variables examined in this study. En ligne : https://dx.doi.org/10.1186/s11689-021-09389-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Genetic counseling as preventive intervention: toward individual specification of transgenerational autism risk [texte imprimé] / Natasha MARRUS, Auteur ; Tychele N. TURNER, Auteur ; Elizabeth FORSEN, Auteur ; Drew BOLSTER, Auteur ; Alison MARVIN, Auteur ; Andrew WHITEHOUSE, Auteur ; Laura KLINGER, Auteur ; Christina A. GURNETT, Auteur ; J.N. CONSTANTINO, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 13 (2021) Mots-clés : Autism Spectrum Disorder/epidemiology/genetics  Autistic Disorder/epidemiology/genetics  Genetic Counseling  Humans  Parents  Prospective Studies  Early detection  Family studies  Personalized medicine  Reproductive health planning  for the Social Responsiveness Scale. Index. décimale : PER Périodiques Résumé : BACKGROUND: Although autism spectrum disorders (ASD) are among the most heritable of all neuropsychiatric syndromes, most affected children are born to unaffected parents. Recently, we reported an average increase of 3-5% over general population risk of ASD among offspring of adults who have first-degree relatives with ASD in a large epidemiologic family sample. A next essential step is to investigate whether there are measurable characteristics of individual parents placing them at higher or lower recurrence risk, as this information could allow more personalized genetic counseling. METHODS: We assembled what is to our knowledge the largest collection of data on the ability of four measurable characteristics of unaffected prospective parents to specify risk for autism among their offspring: (1) sub clinical autistic trait burden, (2) parental history of a sibling with ASD, (3) transmitted autosomal molecular genetic abnormalities, and (4) parental age. Leveraging phenotypic and genetic data in curated family cohorts, we evaluate the respective associations between these factors and child outcome when autism is present in the family in the parental generation. RESULTS: All four characteristics were associated with elevation in offspring risk; however, the magnitude of their predictive power-with the exception of isolated rare inherited pathogenic variants -does not yet reach a threshold that would typically be considered actionable for reproductive decision-making. CONCLUSIONS: Individual specification of risk to offspring of adults in ASD-affected families is not straightforwardly improved by ascertainment of parental phenotype, and it is not yet clear whether genomic screening of prospective parents in families affected by idiopathic ASD is warranted as a clinical standard. Systematic screening of affected family members for heritable pathogenic variants, including rare sex-linked mutations, will identify a subset of families with substantially elevated transmission risk. Polygenic risk scores are only weakly predictive at this time but steadily improving and ultimately may enable more robust prediction either singly or when combined with the risk variables examined in this study. En ligne : https://dx.doi.org/10.1186/s11689-021-09389-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Mapping neural correlates of biological motion perception in autistic children using high-density diffuse optical tomography / Dalin YANG in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 35p. Titre : Mapping neural correlates of biological motion perception in autistic children using high-density diffuse optical tomography Type de document : texte imprimé Auteurs : Dalin YANG, Auteur ; Alexandra M. SVOBODA, Auteur ; Tessa G. GEORGE, Auteur ; Patricia K. MANSFIELD, Auteur ; Muriah D. WHEELOCK, Auteur ; Mariel L. SCHROEDER, Auteur ; Sean M. RAFFERTY, Auteur ; Arefeh SHERAFATI, Auteur ; Kalyan TRIPATHY, Auteur ; Tracy BURNS-YOCUM, Auteur ; Elizabeth FORSEN, Auteur ; John R. PRUETT, Auteur ; Natasha M. MARRUS, Auteur ; Joseph P. CULVER, Auteur ; John N. CONSTANTINO, Auteur ; Adam T. EGGEBRECHT, Auteur Article en page(s) : 35p. Langues : Anglais (eng) Mots-clés : Humans  Tomography, Optical/methods  Male  Child  Female  Motion Perception/physiology  Brain Mapping/methods  Autism Spectrum Disorder/diagnostic imaging/physiopathology  Brain/diagnostic imaging/physiopathology  Autistic Disorder/physiopathology/diagnostic imaging  Magnetic Resonance Imaging/methods  Adolescent  Autism spectrum disorder  Biological motion  High-density diffuse optical tomography  Neuroimaging  Social perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD), a neurodevelopmental disorder defined by social communication deficits plus repetitive behaviors and restricted interests, currently affects 1/36 children in the general population. Recent advances in functional brain imaging show promise to provide useful biomarkers of ASD diagnostic likelihood, behavioral trait severity, and even response to therapeutic intervention. However, current gold-standard neuroimaging methods (e.g., functional magnetic resonance imaging, fMRI) are limited in naturalistic studies of brain function underlying ASD-associated behaviors due to the constrained imaging environment. Compared to fMRI, high-density diffuse optical tomography (HD-DOT), a non-invasive and minimally constraining optical neuroimaging modality, can overcome these limitations. Herein, we aimed to establish HD-DOT to evaluate brain function in autistic and non-autistic school-age children as they performed a biological motion perception task previously shown to yield results related to both ASD diagnosis and behavioral traits. METHODS: We used HD-DOT to image brain function in 46 ASD school-age participants and 49 non-autistic individuals (NAI) as they viewed dynamic point-light displays of coherent biological and scrambled motion. We assessed group-level cortical brain function with statistical parametric mapping. Additionally, we tested for brain-behavior associations with dimensional metrics of autism traits, as measured with the Social Responsiveness Scale-2, with hierarchical regression models. RESULTS: We found that NAI participants presented stronger brain activity contrast (coherent > scrambled) than ASD children in cortical regions related to visual, motor, and social processing. Additionally, regression models revealed multiple cortical regions in autistic participants where brain function is significantly associated with dimensional measures of ASD traits. LIMITATIONS: Optical imaging methods are limited in depth sensitivity and so cannot measure brain activity within deep subcortical regions. However, the field of view of this HD-DOT system includes multiple brain regions previously implicated in both task-based and task-free studies on autism. CONCLUSIONS: This study demonstrates that HD-DOT is sensitive to brain function that both differentiates between NAI and ASD groups and correlates with dimensional measures of ASD traits. These findings establish HD-DOT as an effective tool for investigating brain function in autistic and non-autistic children. Moreover, this study established neural correlates related to biological motion perception and its association with dimensional measures of ASD traits. En ligne : https://dx.doi.org/10.1186/s13229-024-00614-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Mapping neural correlates of biological motion perception in autistic children using high-density diffuse optical tomography [texte imprimé] / Dalin YANG, Auteur ; Alexandra M. SVOBODA, Auteur ; Tessa G. GEORGE, Auteur ; Patricia K. MANSFIELD, Auteur ; Muriah D. WHEELOCK, Auteur ; Mariel L. SCHROEDER, Auteur ; Sean M. RAFFERTY, Auteur ; Arefeh SHERAFATI, Auteur ; Kalyan TRIPATHY, Auteur ; Tracy BURNS-YOCUM, Auteur ; Elizabeth FORSEN, Auteur ; John R. PRUETT, Auteur ; Natasha M. MARRUS, Auteur ; Joseph P. CULVER, Auteur ; John N. CONSTANTINO, Auteur ; Adam T. EGGEBRECHT, Auteur . - 35p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 35p. Mots-clés : Humans  Tomography, Optical/methods  Male  Child  Female  Motion Perception/physiology  Brain Mapping/methods  Autism Spectrum Disorder/diagnostic imaging/physiopathology  Brain/diagnostic imaging/physiopathology  Autistic Disorder/physiopathology/diagnostic imaging  Magnetic Resonance Imaging/methods  Adolescent  Autism spectrum disorder  Biological motion  High-density diffuse optical tomography  Neuroimaging  Social perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD), a neurodevelopmental disorder defined by social communication deficits plus repetitive behaviors and restricted interests, currently affects 1/36 children in the general population. Recent advances in functional brain imaging show promise to provide useful biomarkers of ASD diagnostic likelihood, behavioral trait severity, and even response to therapeutic intervention. However, current gold-standard neuroimaging methods (e.g., functional magnetic resonance imaging, fMRI) are limited in naturalistic studies of brain function underlying ASD-associated behaviors due to the constrained imaging environment. Compared to fMRI, high-density diffuse optical tomography (HD-DOT), a non-invasive and minimally constraining optical neuroimaging modality, can overcome these limitations. Herein, we aimed to establish HD-DOT to evaluate brain function in autistic and non-autistic school-age children as they performed a biological motion perception task previously shown to yield results related to both ASD diagnosis and behavioral traits. METHODS: We used HD-DOT to image brain function in 46 ASD school-age participants and 49 non-autistic individuals (NAI) as they viewed dynamic point-light displays of coherent biological and scrambled motion. We assessed group-level cortical brain function with statistical parametric mapping. Additionally, we tested for brain-behavior associations with dimensional metrics of autism traits, as measured with the Social Responsiveness Scale-2, with hierarchical regression models. RESULTS: We found that NAI participants presented stronger brain activity contrast (coherent > scrambled) than ASD children in cortical regions related to visual, motor, and social processing. Additionally, regression models revealed multiple cortical regions in autistic participants where brain function is significantly associated with dimensional measures of ASD traits. LIMITATIONS: Optical imaging methods are limited in depth sensitivity and so cannot measure brain activity within deep subcortical regions. However, the field of view of this HD-DOT system includes multiple brain regions previously implicated in both task-based and task-free studies on autism. CONCLUSIONS: This study demonstrates that HD-DOT is sensitive to brain function that both differentiates between NAI and ASD groups and correlates with dimensional measures of ASD traits. These findings establish HD-DOT as an effective tool for investigating brain function in autistic and non-autistic children. Moreover, this study established neural correlates related to biological motion perception and its association with dimensional measures of ASD traits. En ligne : https://dx.doi.org/10.1186/s13229-024-00614-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Mate selection and current trends in the prevalence of autism / Elizabeth FORSEN in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 29p. Titre : Mate selection and current trends in the prevalence of autism Type de document : texte imprimé Auteurs : Elizabeth FORSEN, Auteur ; Natasha M. MARRUS, Auteur ; Jacqueline JOYCE, Auteur ; Yi ZHANG, Auteur ; John N. CONSTANTINO, Auteur Article en page(s) : 29p. Langues : Anglais (eng) Mots-clés : Adult  Child  Female  Humans  Male  Autistic Disorder/epidemiology/genetics  California/epidemiology  Hispanic or Latino  Missouri/epidemiology  Prevalence  White  Assortative mating  Autism  Autism prevalence  Mate selection  Racial and ethnic minorities  Responsiveness Scale-2, a quantitative measure of autistic traits. The remaining  authors declare that they have no conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: According to the most recent U.S. CDC surveillance data, the rise in prevalence of childhood autism spectrum disorder among minority children has begun to outpace that of non-Hispanic white children. Since prior research has identified possible differences in the extent of mate selection for autistic traits across families of different ethnicity, this study examined variation in autism related traits in contemporaneous, epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white populations. The purpose was to determine whether discrepancies by ethnicity could contribute to differential increases in prevalence in the current generation of young children. METHODS: Birth records were used to identify all twin pairs born between 2011 and 2013 in California and Missouri. Families were selected at random from pools of English-speaking Hispanic families in California and Non-Hispanic White families in Missouri. Autistic trait data of parents was obtained using the Adult Report Form of the Social Responsiveness Scale (SRS-2). RESULTS: We did not identify a statistically significant difference in the degree of mate selection for autism related traits between Hispanic and non-Hispanic white spousal pairs. However, the degree of spousal correlation observed in this recent cohort was pronounced (on the order of ICC 0.45) and exceeded that typically reported in prior research (on the order of 0.30), surpassing also widely reported estimates for sibling correlation (also on the order of 0.30). LIMITATIONS: The sample did not allow for a direct appraisal of change in the magnitude of spousal correlation over time and the ascertainments of trait burden were derived from spouse report. CONCLUSION: Across two epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white families across two U.S. states (respectively, California and Missouri), the extent of autism-related trait co-variation for parents of the current generation of young children is substantial and exceeds correlations typically observed for siblings. Given the heritability of these traits and their relation to autism risk, societal trends in the degree of mate selection for these traits should be considered as possible contributors to subtle increases in the incidence of autism over time and across generations. En ligne : https://dx.doi.org/10.1186/s13229-024-00607-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Mate selection and current trends in the prevalence of autism [texte imprimé] / Elizabeth FORSEN, Auteur ; Natasha M. MARRUS, Auteur ; Jacqueline JOYCE, Auteur ; Yi ZHANG, Auteur ; John N. CONSTANTINO, Auteur . - 29p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 29p. Mots-clés : Adult  Child  Female  Humans  Male  Autistic Disorder/epidemiology/genetics  California/epidemiology  Hispanic or Latino  Missouri/epidemiology  Prevalence  White  Assortative mating  Autism  Autism prevalence  Mate selection  Racial and ethnic minorities  Responsiveness Scale-2, a quantitative measure of autistic traits. The remaining  authors declare that they have no conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: According to the most recent U.S. CDC surveillance data, the rise in prevalence of childhood autism spectrum disorder among minority children has begun to outpace that of non-Hispanic white children. Since prior research has identified possible differences in the extent of mate selection for autistic traits across families of different ethnicity, this study examined variation in autism related traits in contemporaneous, epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white populations. The purpose was to determine whether discrepancies by ethnicity could contribute to differential increases in prevalence in the current generation of young children. METHODS: Birth records were used to identify all twin pairs born between 2011 and 2013 in California and Missouri. Families were selected at random from pools of English-speaking Hispanic families in California and Non-Hispanic White families in Missouri. Autistic trait data of parents was obtained using the Adult Report Form of the Social Responsiveness Scale (SRS-2). RESULTS: We did not identify a statistically significant difference in the degree of mate selection for autism related traits between Hispanic and non-Hispanic white spousal pairs. However, the degree of spousal correlation observed in this recent cohort was pronounced (on the order of ICC 0.45) and exceeded that typically reported in prior research (on the order of 0.30), surpassing also widely reported estimates for sibling correlation (also on the order of 0.30). LIMITATIONS: The sample did not allow for a direct appraisal of change in the magnitude of spousal correlation over time and the ascertainments of trait burden were derived from spouse report. CONCLUSION: Across two epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white families across two U.S. states (respectively, California and Missouri), the extent of autism-related trait co-variation for parents of the current generation of young children is substantial and exceeds correlations typically observed for siblings. Given the heritability of these traits and their relation to autism risk, societal trends in the degree of mate selection for these traits should be considered as possible contributors to subtle increases in the incidence of autism over time and across generations. En ligne : https://dx.doi.org/10.1186/s13229-024-00607-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

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