Understanding self-reported experiences
: Genetic influences and clinical outcomes

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Environmental adversity is robustly associated with the onset, course and outcomes of numerous mental health disorders. Self-reported measures are widely used as a means of capturing these environmental experiences. Compared to objective assessments, subjectively self-reported environmental adversity is associated with a greater risk of psychopathology. This indicates that the associated risk emerges largely as a product of the subjective experience, rather than the exposure alone. However, there is limited knowledge of why subjective reports of adversity confer a greater risk for poor outcomes, and how this risk relates to associated clinical features or confounding factors, such as genetic influences. By leveraging self-reports of environmental experiences, this thesis aims to further understanding of the pathways from exposure to differential outcomes.

Four empirical studies are presented that each use different methods to investigate clinical and genetic factors associated with self-reported experiences. The first study uses network analysis to explore differences in the presentation of depression and anxiety symptoms associated with self-reported lifetime trauma (Chapter 2). The second part of this thesis focuses on gene-environment interplay in self-reported experiences. Using polygenic scores, associations between retrospective self-reports of childhood trauma and genetic predisposition for personality, psychiatric and cognitive traits are assessed in young adults. By controlling for longitudinally assessed environmental adversity across development, the extent to which these associations are accounted for by gene-environment correlation is explored (Chapter 3).

The investigation of gene-environment interplay is then extended to the experience of positive environments. Using the twin design, the proportion of the heritable component of self-reported life events in adolescence accounted for by genetic influences on sensitivity to environmental influences and internal signals is estimated. Differential genetic overlap between sensitivity traits and the perception of life events as negative or positive is explored (Chapter 4). Finally, genetic influences on self-reported outcomes following treatment for depression and anxiety are investigated through genome-wide association meta-analysis and prediction modelling (Chapter 5). Through these studies, this thesis demonstrates the insights that can be harnessed through subjective reports about the processes underlying differential exposure and response to environmental risks and interventions across the lifespan.
Date of Award1 Jan 2023
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorThalia Eley (Supervisor) & Andrea Danese (Supervisor)

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