Understanding treatment-related phenotypes in depression and anxiety: genetic and longitudinal approaches

Student thesis: Doctoral ThesisDoctor of Philosophy


Depression and anxiety are the most common mental health disorders and represent a substantial burden at both the societal and individual level. Effective treatments are available for depression and anxiety, however, a substantial proportion of patients do not recover. This is partly explainable by individual differences in response to treatment.
Individual differences during psychological therapy have been overlooked in comparison with endpoint outcomes but may be especially informative for clinical decisions and expectations, as well as progress monitoring. The onset and prognosis of depression and anxiety are influenced by a complex interplay of genetic and environmental factors including a large number of genetic variants with individually very small effects. Genetic studies of depression and anxiety require vast sample sizes for sufficient statistical power to detect these effects. Identifying associated genetic variants can elucidate downstream biological pathways and could contribute to prediction models of disorder onset and treatment outcomes. This thesis explores two main themes. First, assessing the use of resource-saving ‘brief phenotypes’ of treatment-related variables to increase sample size and thus power for genetic studies. Second, investigating the existence of individual differences in longitudinal patterns of treatment outcomes during psychological therapy, as evidenced by multiple subgroups of trajectories. Chapter 1 provides an overview of literature and concepts relevant to this thesis. Chapter 2 is a study investigating self- reported medication use in the UK Biobank as a brief phenotype of depression and anxiety.
The analysis presented in Chapter 3 is an investigation of the genetic overlap between symptom severity and functional impairment in a sample of patients with lifetime experience of depression or anxiety. This informs our understanding of using brief measures of symptom severity in genetic studies. The two studies in the second half of the thesis, Chapters 4 and 5, explore whether there are multiple subgroups of patients distinguished by similar outcome trajectories during psychological therapy. For this analysis, electronic treatment records from the NHS Improving Access to Psychological Therapies (IAPT) services were modelled. Chapter 4 uses data from in-person IAPT services, while Chapter 5 is an analysis of patients who received real-time therapy via the internet.
The final chapter presents a discussion of findings from the study chapters in relation to one another, general strengths and limitations, and future directions.
Date of Award1 Dec 2022
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorThalia Eley (Supervisor) & Gerome Breen (Supervisor)

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