Using hierarchical dimensional models to investigate the genomic and neural correlates of transdiagnostic psychiatric phenotypes across the lifespan

Abstract

Hierarchical dimensional models have gained popularity as a data-driven alternative to traditional psychiatric classification systems. The transdiagnostic phenotypes derived from these models demonstrate greater reliability and validity than traditional diagnostic categories and promise to facilitate new discoveries regarding the biological underpinnings of mental illness. Chapter 1 presents a broad overview of hierarchical dimensional models of psychopathology, focusing on important methodological considerations, the advantages of hierarchical models in identifying biological associations, and emphasizing the need to adopt a lifespan approach to this research. Chapter 2 is the first systematic review to investigate the genetic and neural correlates of transdiagnostic dimensions of psychopathology across the lifespan. The review identified a range of biological correlates that have been reported across multiple studies and age groups; however, there were no included studies that investigated these relationships specifically in older adulthood. Chapter 3 presents the first study to investigate the latent hierarchical structure of psychopathology in older adults, examines whether a lower-order dimension capturing cognitive dysfunction can be incorporated into this structure, and examines whether this structure is invariant across four age groups throughout later life. Chapter 4 presents the first study to investigate whether transdiagnostic dimensions of psychopathology are associated with brain structure in older adulthood. Chapter 5 presents the first study to investigate the genomic correlates of transdiagnostic dimensions specifically in older adulthood. Chapters 4-5 additionally examine the utility of hierarchical dimensional models of psychopathology in investigating the relationships between psychopathology and all-cause incident dementia in later life.