Autistic symptoms in early psychosis are associated with mean diffusivity-dominant alterations in white matter tracts implicated in schizophrenia and autism spectrum disorder.

BACKGROUND

Autistic symptoms occur across the psychosis spectrum and are linked to poorer cognitive, social, and clinical outcomes. Although prior studies have mainly examined gray matter, the relationship between autistic symptoms and white matter microstructure remains unclear in early psychosis. We examined node-wise white matter alterations associated with autistic symptom severity using diffusion tensor imaging.

METHODS

We included 126 participants: 48 at clinical high risk for psychosis, 46 with first-episode psychosis, and 32 controls. Autistic symptoms were assessed in the early psychosis group using the Positive and Negative Syndrome Scale Autism Severity Score. Fractional anisotropy and mean diffusivity were derived from diffusion tensor imaging data, and automated fiber quantification extracted node-wise measurements across five tracts. Group differences were examined using age- and sex-adjusted linear regression, and associations with autistic symptoms were evaluated in the early psychosis group using generalized additive models (GAM) adjusted for age, sex, and PANSS positive and general scores.

RESULTS

Compared with controls, the early psychosis group showed increased mean diffusivity across tracts, whereas fractional anisotropy did not differ significantly. In GAMs, autistic symptom severity showed no significant global association with fractional anisotropy but showed spatially heterogeneous associations. Mean diffusivity showed significant positive global and spatially varying associations with autistic symptom severity, particularly in the cingulum bundle, superior longitudinal fasciculus, and arcuate fasciculus.

CONCLUSION

Autistic symptoms in early psychosis were associated with predominantly mean diffusivity-based white matter alterations. These preliminary cross-sectional findings identify potential imaging correlates of autistic symptoms and require replication in larger longitudinal studies.