Leiden University Scholarly Publications

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Roelofs, E.F. (2026)

Untangling the adolescent internalizing brain: investigations on brain networks in youth with anxious and depressive problems

Doctoral Thesis
Internalizing disorders, including anxiety and depressive disorders, frequently emerge during adolescence and are associated with substantial impairments in social, academic, and emotional functioning. This developmental period is marked by profound neurobiological changes, particularly in large-scale brain networks involved in emotion processing and regulation. This thesis investigates structural and functional brain connectivity in adolescents with internalizing disorders, with a focus on white matter microstructure and resting-state functional connectivity. Using longitudinal neuroimaging data, Part 1 examines developmental trajectories of brain networks in adolescents with anxiety and depression compared to healthy peers, revealing associations between baseline connectivity characteristics and subsequent symptom change. Part 2 focuses on social anxiety disorder (SAD) as a prototypical internalizing condition, employing a family-based design and large-scale mega-analysis to...Show moreInternalizing disorders, including anxiety and depressive disorders, frequently emerge during adolescence and are associated with substantial impairments in social, academic, and emotional functioning. This developmental period is marked by profound neurobiological changes, particularly in large-scale brain networks involved in emotion processing and regulation. This thesis investigates structural and functional brain connectivity in adolescents with internalizing disorders, with a focus on white matter microstructure and resting-state functional connectivity. Using longitudinal neuroimaging data, Part 1 examines developmental trajectories of brain networks in adolescents with anxiety and depression compared to healthy peers, revealing associations between baseline connectivity characteristics and subsequent symptom change. Part 2 focuses on social anxiety disorder (SAD) as a prototypical internalizing condition, employing a family-based design and large-scale mega-analysis to evaluate their potential as candidate endophenotypes and to identify alterations in white matter microstructure. Across studies, findings highlight the relevance of fronto-limbic and large-scale network connectivity in adolescent internalizing psychopathology and emphasize the importance of considering developmental timing, symptom comorbidity, and individual variability. Overall, this work advances understanding of the neurobiological mechanisms underlying internalizing disorders in adolescence and provides insights that may inform early identification, prevention, and intervention strategies.
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Neuroimaging
Adolescents
Anxiety
Depression
Internalizing disorders
White matter microstructure
Resting-state functional connectivity
All authors
Roelofs, E.F.
Supervisor
Vermeiren, R.R.J.M.; Wee, N.J.A. van der
Co-supervisor
Bas-Hoogendam, J.M.
Committee
Duijvenvoorde, A.C.K. van; Roelofs, K.; Veltman, D.J.; Vermetten, H.G.J.M.; Westenberg, P.M.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2026-03-11
ISBN (print)
9789465371146
DOI
doi:10.60602/1887-4296562