Longitudinal Associations of Structural and Functional Brain Connectivity With Dimensions of Psychopathology in...

Adolescence is a critical period of neurodevelopment marked by ongoing maturation of structural and functional brain connectivity. Simultaneously, this period is associated with an increase in mental health problems, spanning from subclinical symptoms to diagnosable disorders.

This study investigated longitudinal associations between psychopathology dimensions and voxelwise brain measures related to connectivity across 3 time points (ages 14, 19, and 23) in more than 1500 participants using the IMAGEN dataset. White matter (WM) microstructure was indexed using diffusion metrics quantified along the WM skeleton (N = 1736), while functional connectivity was captured as voxelwise degree centrality (DC) derived from resting-state functional imaging (N = 1510).

Development of WM microstructure was selectively linked to externalizing (but not internalizing) symptoms. Here, higher externalizing symptoms were associated with widespread reductions in fractional anisotropy (FA) across the WM skeleton as well as accelerated decreases in FA in the corticospinal tract over time. In contrast, functional DC was developmentally associated with general, rather than specific, psychopathology in frontal and temporal regions. An increase in total difficulties over time was associated with developmental decrease in DC in bilateral superior frontal gyri. In addition, a positive association between total difficulties and DC in left inferior temporal gyrus was observed in younger, but not older, adolescents or young adults.

These findings highlight the dynamic interplay between brain connectivity development and psychopathology in adolescence, with potential implications for identifying neural markers of risk and resilience during sensitive windows of development.