Psychiatric Comorbidities in Children with Autism Spectrum Disorder and Intellectual Disability

Background: Intellectual disability (ID) is characterised by significant limitations in cognitive functioning, adaptive behaviour, and with significant behavioural difficulties or mental health problems. IMAGINE-ID is a UK national cohort study exploring psychiatric risk in children with ID of known genetic aetiology (CNV and SNV).

Objectives: IMAGINE-ID is a genotype-first study of psychiatric risk. We conducted deep-phenotyping, subsequent to the identification of pathogenic CNV or SNV as a cause of developmental delay. Our objective was to assess the prevalence of ASD in an ID cohort identified through NHS genotyping, and to contrast psychiatric comorbidities in those with and without ASD.

Methods: 2,381 children with ID of known genetic aetiology, confirmed by microarray, have been recruited from UK Regional Genetic Centres. Caregivers completed a standardised psychiatric and developmental history interview (the Development and Wellbeing Assessment - DAWBA). The DAWBA generates probability scores for DSM-5 diagnoses, which are then validated by clinical review. Additional measures include the Strengths and Difficulties Questionnaire (SDQ; child emotional and behavioural adjustment); and the Everyday Feelings Questionnaire (EFQ; parental emotional wellbeing). All measures have been used in national UK studies of child mental health. 1,850 assessments have been completed and 1,049 have been rated by clinicians to date. Mean age of cohort was 9.21 (SD 3.87, range 4-18 years).

Results: Overall, 39% met criteria for ASD, with no significant differences in age, mental age or language ability between children with and without ASD. There was a significant gender bias in children with ASD than without (males predominated; 62.5%, p<0.01). Children with ASD were significantly more likely to meet DSM-5 criteria for any additional psychiatric disorder than children without ASD (44% vs 27%, p<.001): with a significantly higher prevalence of Attention-Deficit/Hyperactivity Disorder (ADHD; 28% vs 17%, p<0.001), Oppositional Defiant Disorder (ODD; 17% vs 5%, p<0.001), Anxiety Disorders (15% vs 8%, p<0.001) and Tic Disorders (5% vs 1.7%, p<0.005). There were no significant prevalence differences between the groups in terms of Obsessive Compulsive Disorder, Depression or Conduct Disorder.

Within-group comparisons on the basis of SDQ total scores showed that emotional and behavioural problems were significantly more severe in children with ASD than those without (p<0.001). A comparison with national UK population data showed that 41% of those with ASD had scores above the 95^th centile in total SDQ score. EFQ scores were significantly higher in caregivers of children with ASD (p<0.001) than in families whose child had ID alone.

Conclusions: A high proportion of children with ID of genetic aetiology meet DSM-5 criteria for an ASD, irrespective of the specific CNV or SNV. Compared with children whose ID is not associated with ASD, and who are of equivalent mental age, there is an excess of specific psychiatric comorbidities, including ADHD, ODD, Anxiety Disorders and Tic Disorders. Parents of children with ID of known genetic origin that is associated with ASD have an enhanced risk of stress-related disorders of mood and feelings, and their parents have an enhanced risk of stress-related disorders of mood and feelings.