Chris Oliver

Purpose: Identifying potential risk markers implicated in the development and maintenance of anxiety will inform theoretical models and intervention development. However, there is an identified gap in the literature exploring this in individuals with moderate-profound intellectual disability (ID). The current study sought to identify correlates of anxiety in this population. Methods: A community-based sample of 165 parents/carers of individuals with ID took part in a cross-sectional questionnaire study exploring the relationships between sensory processing differences, repetitive behaviour, intolerance of uncertainty, health difficulties, and anxiety. Demographic factors such as age and gender, as well as potential covariates including diagnosis and autism characteristics were considered in the analyses. Due to a paucity of validated measures for individuals with moderate-profound ID, analyses were explored across two existing anxiety measures. Results: Diagnosis of genetic syndromes and demographic variables were not consistently significantly associated with anxiety once other factors associated with anxiety were added. Auditory sensory processing differences, intolerance of uncertainty and health difficulties were consistently associated with anxiety. Repetitive behaviour, tactile and visual sensory processing differences were not associated with anxiety, Conclusion: This work may help to inform explanations for differing prevalence rates across groups, whilst fostering an inclusive approach by including individuals with diagnoses associated with ID and autism, who may present to the same clinical services.

Background: Cornelia de Lange syndrome (CdLS) and fragile X syndrome (FXS) are associated with co‐occurring autism and anxiety. In autistic people, intolerance of uncertainty (IU) mediates the relationship between autistic characteristics and anxiety, but it is not known whether this relationship is evident in these genetic syndromes. Understanding the relationship between autism, anxiety and IU is essential to informing the theoretical frameworks of anxiety in rare genetic syndromes and improving clinical interventions. Method: Sixty participants with CdLS or FXS participated in a questionnaire‐based study to examine the association between autistic characteristics, anxiety and IU. Results: IU mediated the association between autism and anxiety in participants with CdLS but not in participants with FXS. Conclusions: These results suggest that other factors may contribute to the autism‐anxiety relationship in FXS, and highlight the merit of syndrome‐specific approaches to the study of anxiety. Recommendations are made for intervention‐based research to ameliorate anxiety in CdLS.

SATB2-associated syndrome (SAS) is a genetic syndrome characterised by intellectual disability, severe speech delay, and palatal and dental problems. Behaviours that challenge (BtC) are reported frequently; however, there is limited research on specific forms of BtC and the correlates of these behaviours. The current study explores correlates of well-defined BtC, self-injury, aggression, and property destruction, in SAS. Eighty-one parents/caregivers of individuals with SAS (53.1% male, Mage 10.12 years) completed questionnaire measures of health, behavioural, emotional, and autism characteristics. Individuals with SAS were grouped based on caregiver responses to the presence or absence of self-injury, aggression, and property destruction on the Challenging Behaviour Questionnaire. Rates of self-injury, aggression and property destruction were 42%, 77% and 49%, respectively. Between-group comparisons were conducted to compare characteristics between behaviour groups. Significantly differing characteristics were entered into separate hierarchical logistic regressions for each form of BtC. Behavioural comparisons indicated variation in the characteristics associated with each behaviour. All hierarchical logistic regression models were significant (p < .001): self-injury (χ²(5) = 38.46, R² = 0.571), aggression (χ²(4) = 25.12, R² = 0.414), property destruction (χ²(4) = 23.70, R² = 0.346), explaining between 34.6% and 57.1% of the variance in behaviour presence. This is the first study to identify correlates of self-injury, aggression, and property destruction in SAS. Variability in the characteristics associated with each behaviour highlights the importance of specificity when examining BtC. Understanding correlates of specific forms of BtC has important implications for informing SAS-associated pathways to behavioural outcomes and the implementation of tailored behavioural interventions.

Background: CHARGE syndrome (OMIM #214800) is a phenotypically complex genetic condition characterised by multi-system, multi-sensory impairments. Behavioural, psychological, cognitive and sleep difficulties are not well delineated and are likely associated with biopsychosocial factors.Methods: This meta-analysis investigated the prevalence of clinical features, physical characteristics and conditions, behavioural, psychological, cognitive and sleep characteristics in CHARGE syndrome, and statistically evaluated directional associations between these characteristics. Pooled prevalence estimates were calculated using reliable, prespecified quality weighting criteria, and meta-regression was conducted to identify associations between characteristics.Results: Of the 42 eligible studies, data could be extracted for 1675 participants. Prevalence estimates were highest for developmental delay (84%), intellectual disability (64%), aggressive behaviour (48%), self-injurious behaviour (44%) and sleep difficulties (45%). Meta-regression indicated significant associations between intellectual disability and choanal atresia, intellectual disability and inner ear anomalies, sleep difficulties and growth deficiency, and sleep difficulties and gross motor difficulties.Conclusions: Our comprehensive review of clinical features, behavioural, psychological, cognitive and physical characteristics, conditions and comorbidities in CHARGE syndrome provides an empirically based foundation to further research and practice.

Background: SATB2-associated syndrome (SAS) is a multisystem neurodevelopmental disorder characterised by intellectual disability, speech delay, and craniofacial anomalies. Although the clinical presentation of SAS is well-delineated, behaviours associated with SAS are less well-defined. Given the varied social profile reported in SAS of a ‘jovial’ predisposition and autistic behaviours, there may be phenotypic overlap with both Angelman syndrome (AS) and non-syndromal autism. This study aimed to describe behaviours in SAS in relation to chronological age and level of ability and contrast aspects of the behavioural phenotype with AS and non-syndromal autism. Methods: Informant report questionnaire measures of behaviour, emotion, and autism characteristics were completed for 81 individuals with SAS (aged 1–36 years; 43 male). Within-group associations were analysed, and categorical data were compared between pre-school (1–5 years), school-age (6–15 years), and adolescent and adult SAS sub-groups (16 years and over). Cross-syndrome subscale and item-level analyses were conducted for 63 individuals with SAS (aged 1–27 years; 31 male), who were matched according to age and level of ability to 63 individuals with AS (aged 2–25 years; 32 male) and 63 individuals with non-syndromal autism (aged 3–26 years; 53 male). Results: In SAS, higher rates of overactivity were moderately associated with lower self-help ability, and higher general anxiety scores were reported for males compared with females. Cross-syndrome subscale analyses uncovered several significant differences (p < .01), with comparatively low rates of stereotyped behaviour, overactivity, insistence on sameness and positive affect, and comparatively greater interest and pleasure and compulsive behaviour in individuals with SAS. Item-level analyses revealed a distinct profile of repetitive and autistic behaviours. Limitations: Developmental analysis was based on a cross-sectional rather than a longitudinal research design, the contribution of pain and sleep to behaviour was not explored, and molecular genetic testing to determine genotype–phenotype behavioural relationships was not possible. Conclusions: This study highlights the importance of behavioural comparisons to well-delineated groups and the utility of fine-grained item-level analyses to elucidate aspects of behaviour that might be syndrome related or shared across neurodevelopmental disorders. Future research is needed to further describe the distinctive repetitive and autistic behavioural phenotype in SAS.

Background: Individuals with Down syndrome (DS) are at significant risk for early onset Alzheimer's disease (AD), likely due to the triplication of genes on chromosome 21 that facilitate AD neuropathology. To aid the effective early diagnosis of dementia in DS, we demonstrate the strategy of using single point assessment of cognitive performance with scoring normed for degree of intellectual disability to generate age related prevalence data for acquired mild cognitive impairment (AMCI).Methods: Four hundred and twelve adults with DS were assessed using the Neuropsychological Assessment of dementia in adults with Intellectual Disability. Normative data, banded by degree of intellectual disability, allowed identification of AMCI by atypical deviation from expected performance.Results: AMCI was evident in approximately 20% of adults with DS aged 40 and under, 40% aged 41–50 and 45% aged 51 and over. Relative risk increased significantly in those aged 46 and over. Analysis of prevalence by 5‐year age bands revealed two peaks for higher prevalence of AMCI.Conclusions: Psychometric data indicate single point assessment of AMCI is possible for the majority of adults with DS. Two peaks for age‐related prevalence of AMCI suggest the risk for onset of AD conferred by trisomy of chromosome 21 is moderated by another factor, possibly ApoE status.

Background: Cornelia de Lange syndrsome (CdLS) is a rare genetic syndrome with notable impaired expressive communication characterised by reduced spoken language. We examined gesture use to refine the description of expressive communication impairments in CdLS.Methods: During conversations, we compared gesture use in people with CdLS to peers with Down syndrome (DS) matched for receptive language and adaptive ability, and typically developing (TD) individuals of similar chronological age.Results: As anticipated the DS and CdLS groups used fewer words during conversation than TD peers (P < .001). However, the CdLS group used twice the number of gestures per 100 words compared with the DS and TD groups (P = .003).Conclusions: Individuals with CdLS have a significantly higher gesture rate than expected given their level of intellectual disability and chronological age. This result indicates the cause of reduced use of spoken language does not extend to all forms of expressive communication.

The assessment of depression in people with severe to profound intellectual disability (severe–profound ID) is challenging, primarily due to inability to report internal states such as mood, feelings of worthlessness and suicidal ideation. This group also commonly presents with challenging behaviours (e.g. aggression and self‐injury) with debate about whether these behaviours should be considered ‘depressive equivalents’ or are sensitive for, but not specific to, depression in severe–profound ID. We conducted a systematic review exploring behaviours associated with depression and low mood in individuals with severe–profound ID. The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (2009) guidelines. Three electronic databases were searched (Embase, PsycINFO and Ovid MEDLINE), and 13 studies were included and rated for quality. Few studies were rated as having high methodological quality. Behaviours captured by standard diagnostic schemes for depression (e.g. Diagnostic and Statistical Manual of Mental Disorders and International Classification of Diseases) showed a relationship with depression in severe–profound ID, including the two core symptoms (depressed affect and anhedonia), as well as irritability, sleep disturbance, psychomotor agitation, reduced appetite and fatigue. Challenging behaviours such as aggression, self‐injury, temper tantrums, screaming and disruptive behaviour were associated with depression. Challenging behaviours show a robust relationship with depression. Whilst these behaviours may suggest an underlying depression, study limitations warrant caution in labelling them as ‘depressive equivalents’. These limitations include not controlling for potential confounds (autism, other affective disorders and pain) and bias associated with comparing depressed/non‐depressed groups on the same behavioural criteria used to initially diagnose and separate these groups. Future studies that use depressive measures designed for ID populations, which control for confounds and which explore low mood irrespective of psychiatric diagnosis, are warranted to better delineate the behaviours associated with depression in this population (PROSPERO 2018: CRD42018103244).

We directly assessed the broader aspects of sociability (social enjoyment, social motivation, social interaction skills and social discomfort) in individuals with Cornelia de Lange (CdLS), fragile X (FXS) and Rubinstein-Taybi syndromes (RTS), and their association with autism characteristics and chronological age in these groups. Individuals with FXS (p < 0.01) and RTS (p < 0.01) showed poorer quality of eye contact compared to individuals with CdLS. Individuals with FXS showed less person and more object attention than individuals with CdLS (p < 0.01). Associations between sociability and autism characteristics and chronological age differed between groups, which may indicate divergence in the development and aetiology of different components of sociability across these groups. Findings indicate that individuals with CdLS, FXS and RTS show unique profiles of sociability.