In vivo white matter microstructure in adolescents with early-onset psychosis: a multi-site mega-analysis

Area of Science:

• Neuroscience
• Psychiatry
• Medical Imaging

Background:

• Early-onset psychosis (EOP) in adolescents (<18 years) is associated with emerging evidence of brain white matter alterations.
• Previous neuroimaging studies have yielded inconclusive results due to methodological variations and small sample sizes.

Purpose of the Study:

• To investigate white matter microstructure differences in adolescents with EOP compared to healthy controls using diffusion tensor imaging (DTI).
• To identify specific white matter regions and diffusion parameters most affected in EOP.
• To explore associations between white matter alterations and clinical variables.

Main Methods:

• A mega-analytic approach pooling harmonized DTI data from 321 adolescents with EOP and 265 healthy controls across nine sites.
• Extraction of mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) from 25 white matter regions of interest.
• ComBat harmonization to adjust for scanner differences, followed by multiple linear regression analyses.

Main Results:

• Widespread lower FA was observed in EOP adolescents compared to controls, with significant effects in the superior longitudinal fasciculus, posterior corona radiata, and superior fronto-occipital fasciculus.
• Higher RD was widespread, alongside more localized increases in MD and AD in EOP.
• Significant effects of diagnostic subgroup, sex, and duration of illness were detected, but not medication status.

Conclusions:

• This study, utilizing the largest EOP DTI sample to date, confirms a profile of widespread white matter microstructure alterations in adolescents with EOP.
• Findings highlight the prominent impact on males with early-onset schizophrenia and those with a shorter duration of illness.
• These results underscore the importance of DTI in understanding the neurobiological underpinnings of EOP.