Genetic and Environmental Factors Related to Child and Parent Mental Health in the Context of Intellectual Disabilities

Abstract

Mental health problems in children and young people (CYP) with intellectual disabilities (ID) and other neurodevelopmental disorders (NDDs) have long been a concern of research and clinical practice. Genetic diagnosis has become increasingly available for this group in the past decade, opening new opportunities to understand the variance of mental health within this population. This thesis aims to explore the complex effect of genetic and environmental factors on mental health problems, in a large cohort of CYP with ID of known genetic origin (IMAGINE-ID), and a smaller group of CYP with rare neurogenetic disorders (RGDs) during the COVID-19 pandemic (CoIN). Within both cohorts, I investigated mental health in CYP with ID/RGDs and their parents/carers, as they both face elevated mental health risks and can be an important source of influence within the family. In Chapter 2, I use structural equation modelling to explore the impact of genetic diagnoses on parental mental health within IMAGINE-ID. I show that genetic variant type and timing of genetic diagnoses significantly influence parental well-being, via parents’ appraisal of the impact of their child’s condition. Parent-perceived impact falls into two dimensions, and the home and distress dimension play a key role in linking genetic diagnosis, CYP phenotypes and parents’ mental health. In Chapter 3, I focus on CYP with rare pathogenic Copy Number Variants (CNVs) in IMAGINE-ID, exploring the genomic predictors of ID/DD and neurodevelopmental and mental health characteristics in this large and diverse group. The results indicate a complex interplay between CNV characteristics, CNV inheritance and socioeconomic status (SES) in predicting child phenotypes. In Chapter 4, also within CNV-associated ID, the focus shifts to the network structure of ID/DD, neurodevelopmental and psychiatric traits in CYP, and the mental health of their parents. Network analysis highlights the inter-correlated nature of these traits and identifies nodes that play a central role in connecting mental health problems within families, including anxiety, language impairments, developmental quotient and autism. Chapter 5 examines the longitudinal mental health trajectories of children with RGDs and their parents during the COVID-19 pandemic in the CoIN study. The results reveal that children with RGDs exhibited a decrease in emotional problems and an increase in prosocial behaviour, while parental mental health fluctuated in response to changing pandemic conditions. Overall, this thesis provides a better understanding of the complex effects of genetic and environmental factors and their interactive influence on mental health in CYP with NDDs, especially ID, and their families. The findings also indicate that statistical and genomic analysis methods can be combined to better predict the risk of neurodevelopmental and mental health problems and the multivariate and bidirectional network relationships between them at individual and family levels.