Childhood intellectual disability and parents' mental health: integrating social, psychological and genetic influences

Baker, Kate; Devine, Rory T.; Ng‐Cordell, Elise; Raymond, F. Lucy; Hughes, Claire

doi:10.1192/bjp.2020.38

Cited by 40 publications

(44 citation statements)

References 37 publications

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“…These findings are consistent with prior work suggesting that it is the confluence of multiple genetic risk factors that increases the likelihood of neurodevelopmental disorders, more broadly [Girirajan et al, 2012]. Interactions with environmental factors related to social and psychological familial aspects should also be considered [Baker, Devine, Ng-Cordell, Raymond, & Hughes, 2020] as a means to evaluate and understand the gene by environment mechanisms [Wender & Veenstra-Vanderweele, 2017]. As a note of caution, this exploratory study serves as a first foray into specifying specific secondary genetic and environmental factors related to the 16p11.2 CNV phenotype.…”

Section: Insarsupporting

confidence: 90%

Evaluating heterogeneity in ASD symptomatology, cognitive ability, and adaptive functioning among 16p11.2 CNV carriers

et al. 2020

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Individuals with 16p11.2 copy number variant (CNV) show considerable phenotypic heterogeneity. Although autism spectrum disorder (ASD) is reported in approximately 20–23% of individuals with 16p11.2 CNVs, ASD‐associated symptoms are observed in those without a clinical ASD diagnosis. Previous work has shown that genetic variation and prenatal and perinatal birth complications influence ASD risk and symptom severity. This study examined the impact of genetic and environmental risk factors on phenotypic heterogeneity among 16p11.2 CNV carriers. Participants included individuals with a 16p11.2 deletion (N = 96) or duplication (N = 77) with exome sequencing from the Simons VIP study. The presence of prenatal factors, perinatal events, additional genetic events, and gender was studied. Regression analyses examined the contribution of each risk factor on ASD symptomatology, cognitive functioning, and adaptive abilities. For deletion carriers, perinatal and additional genetic events were associated with increased ASD symptomatology and decrements in cognitive and adaptive functioning. For duplication carriers, secondary genetic events were associated with greater cognitive impairments. Being female sex was a protective factor for both deletion and duplication carriers. Our findings suggest that ASD‐associated risk factors contribute to the variability in symptom presentation in individuals with 16p11.2 CNVs. Lay Summary There are a wide range of autism spectrum disorder (ASD) symptoms and abilities observed for individuals with genetic changes of the 16p11.2 region. Here, we found perinatal complications contributed to more severe ASD symptoms (deletion carriers) and additional genetic mutations contributed to decreased cognitive abilities (deletion and duplication carriers). A potential protective factor was also observed for females with 16p11.2 variations. Autism Res 2020, 13: 1300–1310. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

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Section: Insarsupporting

confidence: 90%

Evaluating heterogeneity in ASD symptomatology, cognitive ability, and adaptive functioning among 16p11.2 CNV carriers

et al. 2020

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“…ASC are expected to change with chronological and developmental age, perhaps in a gender-modified fashion [ 33 ], necessitating longitudinal studies. Lastly, socioeconomic status and family characteristics such as household structure, parental education, family stress, and parental mental health may also interact with ASC, with complex bidirectional relationships between child and family factors [ 34 ], which may also encompass genetic diagnosis [ 3 ].…”

Section: Limitationsmentioning

confidence: 99%

“…The potential for dual ID-ASD diagnosis recognises that autism characteristics vary within the ID population and are not an inevitable consequence of low cognitive ability and adaptive impairments. Understanding autism within the ID population is important, because autism predicts the complexity of educational, occupational, and social support needs [ 2 ] and influences the well-being of family carers [ 3 ]. One factor which can influence behavioural phenotypes, including autism, is the aetiology of each individual’s ID.…”

Section: Introductionmentioning

confidence: 99%

Gene functional networks and autism spectrum characteristics in young people with intellectual disability: a dimensional phenotyping study

et al. 2020

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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.

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“…ASC are expected to change with chronological and developmental age, perhaps in a gender-modified fashion (32), necessitating longitudinal studies. Lastly, socioeconomic status and family characteristics such as household structure, parental education, family stress and parental mental health may also interact with ASC, with complex bidirectional relationships between child and family factors (33), which may also encompass genetic diagnosis (3).…”

Section: Limitationsmentioning

confidence: 99%

“…Intellectual disability (ID, defined as IQ <70 plus impaired adaptive function) and autism spectrum disorder (ASD, defined as persistent deficits in social communication and social interaction plus restricted, repetitive behaviours, interests, or activities) frequently co-occur, but are not synonymous (1). Understanding autism within the ID population is important, because autism predicts the complexity of educational, occupational and social support needs (2), and influences the well-being of family carers (3). One factor which can influence behavioural phenotypes, including autism, is the aetiology of each individual's ID.…”

Section: Introductionmentioning

confidence: 99%

Gene functional networks and autism spectrum characteristics in young people with intellectual disability

Brkić

Ng‐Cordell

O’Brien

et al. 2020

Preprint

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BackgroundGenes associated with Intellectual disability (ID) can be grouped into networks according to gene function. This study asked 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. MethodsChildren 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 (AIC) 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. ResultsWe 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. ConclusionWe report that gene functional networks can predict Inflexibility, but not other ASC dimensions.Contrasting behavioural associations within each group suggests 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.Affiliations:

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Childhood intellectual disability and parents' mental health: integrating social, psychological and genetic influences

Cited by 40 publications

References 37 publications

Evaluating heterogeneity in ASD symptomatology, cognitive ability, and adaptive functioning among 16p11.2 CNV carriers

Evaluating heterogeneity in ASD symptomatology, cognitive ability, and adaptive functioning among 16p11.2 CNV carriers

Gene functional networks and autism spectrum characteristics in young people with intellectual disability: a dimensional phenotyping study

Gene functional networks and autism spectrum characteristics in young people with intellectual disability

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