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=3.0×10−6-0.05) and DTI fractional anisotropy (p-values range=4.2×10−4-0.03). 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the NIMH R01 MH129636 ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: the Philadelphia Neurodevelopmental Cohort I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors