Adolescent brain and depression: a neuroimaging approach to understanding biological and psychosocial risk factors

Abstract

Adolescence is a period of significant neurodevelopment and increased vulnerability to the onset of depression. However, the neural underpinnings of depression during adolescence and the associated risk factors are not well understood. The aim of this PhD research was to fill this knowledge gap by examining biological and psychosocial factors associated with the emergence of depression during adolescence.

Using a large, population-based sample, the Adolescent Brain Cognitive Development (ABCD) Study, my doctoral work found that depression in early adolescence is associated with similar neuroimaging findings (cortical and white matter microstructural features) to those seen in adult depression samples. Further, the work in this thesis demonstrated that earlier pubertal timing is associated with an increased risk for later depression in adolescence. While earlier pubertal timing was also related to structural brain features, brain structure was not found to mediate the observed association between early pubertal timing and later depressive symptoms. This finding highlights the important role that other aspects of a young person’s biology, psychology and social world may play, and should be explored in future work.

This thesis also investigated how dynamic functional brain networks relate to irritability in adolescent depression using a co-produced youth-researcher design. In this pilot study, I first worked with young people to develop a novel fMRI irritability task that reflected the social nature of irritability in adolescence. Using a local sample of youth with depressive symptoms, I found that dynamic functional brain networks differed between the irritability task and a standard resting state scan, which provides preliminary evidence for validation of this novel task. Finally, my work demonstrated that properties of dynamic brain networks related to emotion regulation and cognitive control were associated with youth depressive symptoms and irritable mood.

Taken together, the findings of this thesis suggest that neuroanatomical differences may be present early in the disease course of depression and that biological factors, such as early pubertal development, relate to depression risk. Moreover, this work provides preliminary evidence to suggest that alterations in dynamic brain network properties are associated with depressive symptoms and irritability in adolescence. Further, this doctoral research highlights the importance of co-produced study designs in developmental cognitive neuroscience. This work makes an important contribution to our understanding of the factors associated with the emergence of depression during adolescence, which lays a strong foundation upon which to base future longitudinal research.