Age-associated alterations in thalamocortical structural connectivity in psychosis-spectrum youths

Objective: Psychotic symptoms typically emerge in adolescence when connections between the thalamus and cortex are still maturing. The extent to which thalamocortical connectivity differences observed in psychosis occur as a function of age-associated alterations is not fully understood. Methods: We analyzed diffusion-weighted imaging data from 1254 participants 8-23 years old (typically developing youth: N=626, psychosis-spectrum youth: N=329, other psychopathology: N=299) from the Philadelphia Neurodevelopmental Cohort. Using deterministic fiber tractography, we modeled eight tracts between the thalamus and cortical regions of interest. We extracted diffusion spectrum imaging (DSI) and conventional diffusion tensor imaging (DTI) measures. We used generalized additive models to determine group and age-associated differences in thalamocortical connectivity. Results: Compared to typically developing youth and youth with other psychopathologies, psychosis-spectrum youth exhibited thalamocortical reductions in DSI global fractional anisotropy (p-values range=3.0x10-6-0.05) and DTI fractional anisotropy (p-values range=4.2x10-4-0.03). Compared to typically developing youth, psychosis-spectrum youth exhibited shallower thalamus-prefrontal age-associated increases in DSI global fractional anisotropy and DTI fractional anisotropy during middle childhood, and steeper thalamus-prefrontal age-associated increases in those measures during adolescence. Both typically developing youth and youth with other psychopathologies exhibited decreases in mean and radial diffusivity in thalamus-frontal tracts during adolescence; psychosis-spectrum youth failed to show these age-related decreases. Conclusion: Our findings suggest group differences and altered age-related patterns of thalamocortical white matter connectivity in psychosis-spectrum youth. Consistent alterations present as early as middle childhood and altered age-associated patterns during adolescence and young adulthood may contribute to the disruptions in thalamocortical connectivity observed in adults with psychosis.

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