Alterations of white matter microstructure have been reported in the psychosis spectrum. However, the development of these alterations during preclinical stages remains poorly understood. The framework proposed by schizotypy research as the personality base for liability to develop psychosis spectrum disorders offers 3 interconnected dimensions thought to impact neurodevelopment, affording an opportunity to investigate premorbid risk.
In this study, 102 typically developing individuals aged between 12 and 20 y.o. at baseline were scanned longitudinally between 1 and 4 times, and schizotypy was assessed at each visit. Ten white matter tracts were reconstructed using TRACULA, and mixed model regression was used to characterize age-related changes in main diffusion parameters (ie, fractional anisotropy [FA]). Estimated longitudinal trajectories of the 3 dimensions of schizotypy were tested for different trajectories of diffusion parameters as a function of age.
Positive schizotypy trajectory was the most strongly decreased when FA in the anterior thalamic radiation (atr-FA) increased in young adults compared with a moderate decrease in younger participants. Furthermore, in adolescents, disorganized schizotypy followed a steep increase when atr-FA increased, while in the older participants, it decreased as a function of atr-FA. Independent of age, intraindividual positive schizotypy was further longitudinally negatively associated with FA in the cingulate gyrus, and disorganized schizotypy was positively associated with FA in the superior longitudinal fasciculus.
Given that abnormalities in fronto-thalamo-cingulate subcircuit are present in schizophrenia and converters to psychosis, our results support the hypothesis of schizotypy as a personality base risk to develop psychosis.