Association between sleep disturbances and gray matter volume in individuals at clinical high-risk for psychosis and healthy controls: A longitudinal MRI study (NAPLS-3)

Objective

Sleep disturbances and brain alterations are common in psychotic disorders and individuals at clinical high risk for psychosis (CHR-P). It remains unclear whether gray matter volume changes are inherent to psychosis or partly driven by sleep disturbances. This study investigated whether sleep disturbances contribute to progressive structural brain changes.

Methods

Data were obtained from the North American Prodrome Longitudinal Study (NAPLS-3), including 507 CHR-P individuals (mean age 19; 56.0 % male) and 81 healthy controls (HC) (mean age 19; 49.4 % male), assessed with the Pittsburgh Sleep Quality Index (PSQI) and 3 T structural MRI at baseline and prospectively for 8 months. Cross-sectional associations between sleep and gray matter volume were assessed with whole-brain voxel-based morphometry analysis. Longitudinal associations between persistent sleep disturbances and thalamus, hippocampus, and cerebellum volume were examined using linear mixed models.

Results

Sleep disturbances were highly prevalent in CHR-P (mean PSQI = 7.45) and more common than in HC (p < .001). No significant cross-sectional or longitudinal associations were observed between sleep disturbances and gray matter volume in CHR-P nor HC. Exploratory analyses showed that higher PSQI scores were associated with increased odds of conversion to psychosis (OR = 1.059, p = .040).

Conclusions

Our findings indicate no association between sleep disturbances and gray matter volume in CHR-P individuals or HC. This negative result suggests that sleep problems, though prevalent and predictive of psychosis risk, likely act through mechanisms other than structural brain changes, underscoring their value as accessible targets for early intervention.