Neurodevelopmental trajectories of adolescent mental health

Adolescence is a critical period for the emergence of mental health problems. However, the neurobiological, social, and behavioral mechanisms underlying their onset, heterogeneity, and long-term course remain incompletely understood. This thesis leverages large-scale longitudinal data from the Adolescent Brain Cognitive Development study, complemented by adult data from the UK Biobank, to investigate when and how deviations in brain development occur, how they relate to mental health outcomes, and to what extent early risk can be predicted.
Across six chapters, multimodal MRI, machine learning, transcriptomic mapping, and behavioral data were integrated to provide a developmental and transdiagnostic perspective on mental health problems. Longitudinal neuroimaging analyses revealed that the onset of mental health problems often coincides with shared and problem-specific neurodevelopmental changes. Imaging–transcriptomic analyses linked neurodevelopmental changes associated with ADHD and conduct problems onset to distinct molecular pathways. Meanwhile, unsupervised analyses in typically developing youth demonstrated that socioeconomic and family-related factors are associated with different functional brain development.
Supervised prediction models showed that behavioral symptoms can predict later mental health onset, whereas neuroimaging contributed limited predictive value. Further analyses addressing comorbidity indicated that anxiety, rather than depression, drives functional brain alterations in adults. Finally, prediction of symptom persistence showed that behavioral measures exhibit reduced predictive power, whereas neuroimaging may offer additional information on chronic symptom trajectories.
Together, this thesis advances understanding of adolescent mental health by clarifying the developmental timing, biological basis, and predictive limits of mental health problems, and provides clinically relevant insights into early identification, prevention, and intervention.