Salahuddin Mohammad: Deciphering Adult Autism: Exploring Polygenic Risk, Brain Structure, Well-being, Migraine, and Mental Health Disorders

Abstract

This research work comprises four studies investigating mental health disorders, with a particular focus on Autism Spectrum Disorder (ASD, hereafter referred to as autism). The research integrates epidemiological perspectives and genetic frameworks to explore connections with well-being, conditions such as migraine, and neuroanatomical brain structure changes in adulthood, utilizing data from the large European population cohort, UK Biobank, with over half a million participants.

Paper I examined the relationship between job satisfaction, job tenure, and 16 self-reported physician posed diagnosed mental health conditions. The findings show that Neurotic & Stress Disorders, Eating Disorders, and Other Mental Health Disorders are strongly associated with lower job satisfaction and shorter job tenure, highlighting the impact of mental health on workplace participation. Personality trait neuroticism significantly influences job satisfaction but not job tenure.

Paper II explored the relationship between genetic predispositions for autism and five well-being traits (neuroticism, depression, loneliness, life satisfaction, and positive affect). Polygenic risk scores (PRS) for autism were significantly associated with decreased well-being, particularly an increased risk of negative traits such as neuroticism and depression, and reduced positive traits such as life satisfaction, highlighting the genetic basis of well-being in individuals with autism.

Paper III examined the genetic link between autism and migraine, revealing that individuals with a genetic predisposition for autism have an increased risk of migraine, including both major types, migraine with and without aura. While no moderating effect of sex was found, personality trait neuroticism significantly mediated the relationship between autism and migraine, emphasizing the complex genetic and pathophysiological connections between autism and migraine, with neuroticism playing a key role in mediating this association.

Paper IV investigated the association between autism polygenic risk scores and brain volume alterations in the cerebellum, brainstem, and global brain structures in adults. The results demonstrated significant correlations, with higher autism PRS linked to reduced brain volumes, particularly in the cerebellum and brainstem, highlighting the genetic influence on neuroanatomical changes in autism adulthood.

These studies highlight the intricate connections between mental health, genetics, and brain structure, offering valuable insights for improving workplace participation and well-being in individuals with mental health issues including autism.