Genetic and environmental contributors to co-occurring depression in autism spectrum disorder

Underwood, Jack ORCID: https://orcid.org/0000-0003-1731-6039 2025. Genetic and environmental contributors to co-occurring depression in autism spectrum disorder. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Autistic individuals have elevated prevalences of co-occurring mental health problems, notably depression and anxiety, but what may be causing this elevation is less well examined. The aim of this thesis was to establish the impact of specific identified genomic (polygenic score for autism and depression) and socioenvironmental (socioeconomic deprivation and childhood trauma) factors on depression prevalence, phenotype and symptom severity in autistic adults. In analyses of 501 autistic individuals with genotypic and phenotypic data recruited from the National Centre for Mental Health (NCMH) cohort, common genetic variants (as a polygenic score) associated with depression (PGSMDD) showed no association with lifetime depression diagnosis or phenotype. By contrast, PGS for autism (PGSASD) showed some protective association against depression in autistic men. In a cross-disorder sample, DRAGON-Data, collated from 15 separate studies of different mental health conditions, neither PGSASD nor PGSMDD had a robust effect on depression diagnosis or phenotype. In a subset of the NCMH sample whom I re-contacted and assessed with a battery of measures autism trait severity was strongly positively associated with current depression symptoms, but not lifetime depression diagnosis. I demonstrated depression was highly prevalent in autistic individuals in Wales, using healthcare record data drawn from the SAIL databank, and that it is associated with greater socioeconomic deprivation. In the Avon Longitudinal Study of Parents and Children (ALSPAC), I again showed that worse depression symptom severity is associated with greater autism trait severity, particularly social communication difficulties, and that childhood trauma had a mediating effect on the relationship between the traits and depression. The findings of this PhD add to the evidence around co-occurring depression in autism, generate hypotheses for future work exploring the relationship between autism traits, childhood trauma, socioeconomic deprivation, and depression, and provides potential targets for future interventions to reduce depression severity in autistic individuals.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Medicine
Date of First Compliant Deposit:	27 May 2025
Last Modified:	27 May 2025 08:55
URI:	https://orca.cardiff.ac.uk/id/eprint/178503

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