Annual Research Review: Rare genotypes and childhood psychopathology – uncovering diverse developmental mechanisms of ADHD risk / Gaia SCERIF in Journal of Child Psychology and Psychiatry, 56-3 (March 2015)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 56-3 (March 2015) . - p.251-273 Titre : Annual Research Review: Rare genotypes and childhood psychopathology – uncovering diverse developmental mechanisms of ADHD risk Type de document : Texte imprimé et/ou numérique Auteurs : Gaia SCERIF, Auteur ; Kate BAKER, Auteur Article en page(s) : p.251-273 Langues : Anglais (eng) Mots-clés : Rare genotypes  causal pathways  developmental mechanisms  ADHD risk Index. décimale : PER Périodiques Résumé : Background Through the increased availability and sophistication of genetic testing, it is now possible to identify causal diagnoses in a growing proportion of children with neurodevelopmental disorders. In addition to developmental delay and intellectual disability, many genetic disorders are associated with high risks of psychopathology, which curtail the wellbeing of affected individuals and their families. Beyond the identification of significant clinical needs, understanding the diverse pathways from rare genetic mutations to cognitive dysfunction and emotional–behavioural disturbance has theoretical and practical utility. Methods We overview (based on a strategic search of the literature) the state-of-the-art on causal mechanisms leading to one of the most common childhood behavioural diagnoses – attention deficit hyperactivity disorder (ADHD) – in the context of specific genetic disorders. We focus on new insights emerging from the mapping of causal pathways from identified genetic differences to neuronal biology, brain abnormalities, cognitive processing differences and ultimately behavioural symptoms of ADHD. Findings First, ADHD research in the context of rare genotypes highlights the complexity of multilevel mechanisms contributing to psychopathology risk. Second, comparisons between genetic disorders associated with similar psychopathology risks can elucidate convergent or distinct mechanisms at each level of analysis, which may inform therapeutic interventions and prognosis. Third, genetic disorders provide an unparalleled opportunity to observe dynamic developmental interactions between neurocognitive risk and behavioural symptoms. Fourth, variation in expression of psychopathology risk within each genetic disorder points to putative moderating and protective factors within the genome and the environment. Conclusion A common imperative emerging within psychopathology research is the need to investigate mechanistically how developmental trajectories converge or diverge between and within genotype-defined groups. Crucially, as genetic predispositions modify interaction dynamics from the outset, longitudinal research is required to understand the multi-level developmental processes that mediate symptom evolution. En ligne : http://dx.doi.org/10.1111/jcpp.12374 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=259 [article] Annual Research Review: Rare genotypes and childhood psychopathology – uncovering diverse developmental mechanisms of ADHD risk [Texte imprimé et/ou numérique] / Gaia SCERIF, Auteur ; Kate BAKER, Auteur . - p.251-273. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 56-3 (March 2015) . - p.251-273 Mots-clés : Rare genotypes  causal pathways  developmental mechanisms  ADHD risk Index. décimale : PER Périodiques Résumé : Background Through the increased availability and sophistication of genetic testing, it is now possible to identify causal diagnoses in a growing proportion of children with neurodevelopmental disorders. In addition to developmental delay and intellectual disability, many genetic disorders are associated with high risks of psychopathology, which curtail the wellbeing of affected individuals and their families. Beyond the identification of significant clinical needs, understanding the diverse pathways from rare genetic mutations to cognitive dysfunction and emotional–behavioural disturbance has theoretical and practical utility. Methods We overview (based on a strategic search of the literature) the state-of-the-art on causal mechanisms leading to one of the most common childhood behavioural diagnoses – attention deficit hyperactivity disorder (ADHD) – in the context of specific genetic disorders. We focus on new insights emerging from the mapping of causal pathways from identified genetic differences to neuronal biology, brain abnormalities, cognitive processing differences and ultimately behavioural symptoms of ADHD. Findings First, ADHD research in the context of rare genotypes highlights the complexity of multilevel mechanisms contributing to psychopathology risk. Second, comparisons between genetic disorders associated with similar psychopathology risks can elucidate convergent or distinct mechanisms at each level of analysis, which may inform therapeutic interventions and prognosis. Third, genetic disorders provide an unparalleled opportunity to observe dynamic developmental interactions between neurocognitive risk and behavioural symptoms. Fourth, variation in expression of psychopathology risk within each genetic disorder points to putative moderating and protective factors within the genome and the environment. Conclusion A common imperative emerging within psychopathology research is the need to investigate mechanistically how developmental trajectories converge or diverge between and within genotype-defined groups. Crucially, as genetic predispositions modify interaction dynamics from the outset, longitudinal research is required to understand the multi-level developmental processes that mediate symptom evolution. En ligne : http://dx.doi.org/10.1111/jcpp.12374 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=259

Gene functional networks and autism spectrum characteristics in young people with intellectual disability: a dimensional phenotyping study / Diandra BRKI? in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) Titre : Gene functional networks and autism spectrum characteristics in young people with intellectual disability: a dimensional phenotyping study Type de document : Texte imprimé et/ou numérique Auteurs : Diandra BRKI?, Auteur ; Elise NG-CORDELL, Auteur ; Sinéad O'BRIEN, Auteur ; Gaia SCERIF, Auteur ; Duncan E. ASTLE, Auteur ; Kate BAKER, Auteur Langues : Anglais (eng) Mots-clés : Anxiety  Autism dimensions  Genetics  Hyperactivity  Intellectual disability Index. décimale : PER Périodiques Résumé : BACKGROUND: The relationships between specific genetic aetiology and phenotype in neurodevelopmental disorders are complex and hotly contested. Genes associated with intellectual disability (ID) can be grouped into networks according to gene function. This study explored whether individuals with ID show differences in autism spectrum characteristics (ASC), depending on the functional network membership of their rare, pathogenic de novo genetic variants. METHODS: Children and young people with ID of known genetic origin were allocated to two broad functional network groups: synaptic physiology (n?=?29) or chromatin regulation (n?=?23). We applied principle components analysis to the Social Responsiveness Scale to map the structure of ASC in this population and identified three components-Inflexibility, Social Understanding and Social Motivation. We then used Akaike information criterion to test the best fitting models for predicting ASC components, including demographic factors (age, gender), non-ASC behavioural factors (global adaptive function, anxiety, hyperactivity, inattention), and gene functional networks. RESULTS: We found that, when other factors are accounted for, the chromatin regulation group showed higher levels of Inflexibility. We also observed contrasting predictors of ASC within each network group. Within the chromatin regulation group, Social Understanding was associated with inattention, and Social Motivation was predicted by hyperactivity. Within the synaptic group, Social Understanding was associated with hyperactivity, and Social Motivation was linked to anxiety. LIMITATIONS: Functional network definitions were manually curated based on multiple sources of evidence, but a data-driven approach to classification may be more robust. Sample sizes for rare genetic diagnoses remain small, mitigated by our network-based approach to group comparisons. This is a cross-sectional study across a wide age range, and longitudinal data within focused age groups will be informative of developmental trajectories across network groups. CONCLUSION: We report that gene functional networks can predict Inflexibility, but not other ASC dimensions. Contrasting behavioural associations within each group suggest network-specific developmental pathways from genomic variation to autism. Simple classification of neurodevelopmental disorder genes as high risk or low risk for autism is unlikely to be valid or useful. En ligne : http://dx.doi.org/10.1186/s13229-020-00403-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438 [article] Gene functional networks and autism spectrum characteristics in young people with intellectual disability: a dimensional phenotyping study [Texte imprimé et/ou numérique] / Diandra BRKI?, Auteur ; Elise NG-CORDELL, Auteur ; Sinéad O'BRIEN, Auteur ; Gaia SCERIF, Auteur ; Duncan E. ASTLE, Auteur ; Kate BAKER, Auteur. Langues : Anglais (eng) in Molecular Autism > 11 (2020) Mots-clés : Anxiety  Autism dimensions  Genetics  Hyperactivity  Intellectual disability Index. décimale : PER Périodiques Résumé : BACKGROUND: The relationships between specific genetic aetiology and phenotype in neurodevelopmental disorders are complex and hotly contested. Genes associated with intellectual disability (ID) can be grouped into networks according to gene function. This study explored whether individuals with ID show differences in autism spectrum characteristics (ASC), depending on the functional network membership of their rare, pathogenic de novo genetic variants. METHODS: Children and young people with ID of known genetic origin were allocated to two broad functional network groups: synaptic physiology (n?=?29) or chromatin regulation (n?=?23). We applied principle components analysis to the Social Responsiveness Scale to map the structure of ASC in this population and identified three components-Inflexibility, Social Understanding and Social Motivation. We then used Akaike information criterion to test the best fitting models for predicting ASC components, including demographic factors (age, gender), non-ASC behavioural factors (global adaptive function, anxiety, hyperactivity, inattention), and gene functional networks. RESULTS: We found that, when other factors are accounted for, the chromatin regulation group showed higher levels of Inflexibility. We also observed contrasting predictors of ASC within each network group. Within the chromatin regulation group, Social Understanding was associated with inattention, and Social Motivation was predicted by hyperactivity. Within the synaptic group, Social Understanding was associated with hyperactivity, and Social Motivation was linked to anxiety. LIMITATIONS: Functional network definitions were manually curated based on multiple sources of evidence, but a data-driven approach to classification may be more robust. Sample sizes for rare genetic diagnoses remain small, mitigated by our network-based approach to group comparisons. This is a cross-sectional study across a wide age range, and longitudinal data within focused age groups will be informative of developmental trajectories across network groups. CONCLUSION: We report that gene functional networks can predict Inflexibility, but not other ASC dimensions. Contrasting behavioural associations within each group suggest network-specific developmental pathways from genomic variation to autism. Simple classification of neurodevelopmental disorder genes as high risk or low risk for autism is unlikely to be valid or useful. En ligne : http://dx.doi.org/10.1186/s13229-020-00403-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438

Shaping long-term primate development: Telomere length trajectory as an indicator of early maternal maltreatment and predictor of future physiologic regulation / Stacy S. DRURY in Development and Psychopathology, 29-5 (December 2017)  

Public ISBD [article]  inDevelopment and Psychopathology > 29-5 (December 2017) . - p.1539-1551 Titre : Shaping long-term primate development: Telomere length trajectory as an indicator of early maternal maltreatment and predictor of future physiologic regulation Type de document : Texte imprimé et/ou numérique Auteurs : Stacy S. DRURY, Auteur ; Brittany R. HOWELL, Auteur ; Christopher JONES, Auteur ; Kyle ESTEVES, Auteur ; Elyse MORIN, Auteur ; Reid SCHLESINGER, Auteur ; Jerrold S. MEYER, Auteur ; Kate BAKER, Auteur ; Mar M. SANCHEZ, Auteur Article en page(s) : p.1539-1551 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : The molecular, neurobiological, and physical health impacts of child maltreatment are well established, yet mechanistic pathways remain inadequately defined. Telomere length (TL) decline is an emerging molecular indicator of stress exposure with definitive links to negative health outcomes in maltreated individuals. The multiple confounders endemic to human maltreatment research impede the identification of causal pathways. This study leverages a unique randomized, cross-foster, study design in a naturalistic translational nonhuman primate model of infant maltreatment. At birth, newborn macaques were randomly assigned to either a maltreating or a competent control mother, balancing for sex, biological mother parenting history, and social rank. Offspring TL was measured longitudinally across the first 6 months of life (infancy) from peripheral blood. Hair cortisol accumulation was also determined at 6, 12, and 18 months of age. TL decline was greater in animals randomized to maltreatment, but also interacted with biological mother group. Shorter TL at 6 months was associated with higher mean cortisol levels through 18 months (juvenile period) when controlling for relevant covariates. These results suggest that even under the equivalent social, nutritional, and environmental conditions feasible in naturalistic translational nonhuman primate models, early adverse caregiving results in lasting molecular scars that foreshadow elevated health risk and physiologic dysregulation. En ligne : http://dx.doi.org/10.1017/S0954579417001225 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=323 [article] Shaping long-term primate development: Telomere length trajectory as an indicator of early maternal maltreatment and predictor of future physiologic regulation [Texte imprimé et/ou numérique] / Stacy S. DRURY, Auteur ; Brittany R. HOWELL, Auteur ; Christopher JONES, Auteur ; Kyle ESTEVES, Auteur ; Elyse MORIN, Auteur ; Reid SCHLESINGER, Auteur ; Jerrold S. MEYER, Auteur ; Kate BAKER, Auteur ; Mar M. SANCHEZ, Auteur . - p.1539-1551. Langues : Anglais (eng) in Development and Psychopathology > 29-5 (December 2017) . - p.1539-1551 Index. décimale : PER Périodiques Résumé : The molecular, neurobiological, and physical health impacts of child maltreatment are well established, yet mechanistic pathways remain inadequately defined. Telomere length (TL) decline is an emerging molecular indicator of stress exposure with definitive links to negative health outcomes in maltreated individuals. The multiple confounders endemic to human maltreatment research impede the identification of causal pathways. This study leverages a unique randomized, cross-foster, study design in a naturalistic translational nonhuman primate model of infant maltreatment. At birth, newborn macaques were randomly assigned to either a maltreating or a competent control mother, balancing for sex, biological mother parenting history, and social rank. Offspring TL was measured longitudinally across the first 6 months of life (infancy) from peripheral blood. Hair cortisol accumulation was also determined at 6, 12, and 18 months of age. TL decline was greater in animals randomized to maltreatment, but also interacted with biological mother group. Shorter TL at 6 months was associated with higher mean cortisol levels through 18 months (juvenile period) when controlling for relevant covariates. These results suggest that even under the equivalent social, nutritional, and environmental conditions feasible in naturalistic translational nonhuman primate models, early adverse caregiving results in lasting molecular scars that foreshadow elevated health risk and physiologic dysregulation. En ligne : http://dx.doi.org/10.1017/S0954579417001225 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=323

Social and emotional characteristics of girls and young women with DDX3X-associated intellectual disability: a descriptive and comparative study / Elise NG-CORDELL in Journal of Autism and Developmental Disorders, 53-8 (August 2023)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 53-8 (August 2023) . - p.3208-3219 Titre : Social and emotional characteristics of girls and young women with DDX3X-associated intellectual disability: a descriptive and comparative study Type de document : Texte imprimé et/ou numérique Auteurs : Elise NG-CORDELL, Auteur ; Anna KOLESNIK-TAYLOR, Auteur ; Sinéad O?BRIEN, Auteur ; Duncan ASTLE, Auteur ; Gaia SCERIF, Auteur ; Kate BAKER, Auteur Article en page(s) : p.3208-3219 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : DDX3X variants are a common cause of intellectual disability (ID) in females, and have been associated with autism spectrum disorder and emotional-behavioural difficulties. In this study, we compared phenotypic data for 23 females with DDX3X variants, to 23 females with ID and other genetic diagnoses. We found a wide range of adaptive, social and emotional function within the DDX3X group. Autism characteristics did not differ between DDX3X and comparison groups, while levels of anxiety and self-injurious behaviour (SIB) were significantly higher in the DDX3X group. Within the DDX3X group, adaptive function, autism characteristics, anxiety and SIB scores were positively correlated, with evidence for group-specific associations with SIB. Future work is warranted to explore the multilevel mechanisms contributing to social and emotional development in individuals with DDX3X variants. En ligne : https://doi.org/10.1007/s10803-022-05527-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=508 [article] Social and emotional characteristics of girls and young women with DDX3X-associated intellectual disability: a descriptive and comparative study [Texte imprimé et/ou numérique] / Elise NG-CORDELL, Auteur ; Anna KOLESNIK-TAYLOR, Auteur ; Sinéad O?BRIEN, Auteur ; Duncan ASTLE, Auteur ; Gaia SCERIF, Auteur ; Kate BAKER, Auteur . - p.3208-3219. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 53-8 (August 2023) . - p.3208-3219 Index. décimale : PER Périodiques Résumé : DDX3X variants are a common cause of intellectual disability (ID) in females, and have been associated with autism spectrum disorder and emotional-behavioural difficulties. In this study, we compared phenotypic data for 23 females with DDX3X variants, to 23 females with ID and other genetic diagnoses. We found a wide range of adaptive, social and emotional function within the DDX3X group. Autism characteristics did not differ between DDX3X and comparison groups, while levels of anxiety and self-injurious behaviour (SIB) were significantly higher in the DDX3X group. Within the DDX3X group, adaptive function, autism characteristics, anxiety and SIB scores were positively correlated, with evidence for group-specific associations with SIB. Future work is warranted to explore the multilevel mechanisms contributing to social and emotional development in individuals with DDX3X variants. En ligne : https://doi.org/10.1007/s10803-022-05527-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=508

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