In vivo white matter microstructure in adolescents with early-onset psychosis: a multi-site mega-analysis via the ENIGMA Consortium.

BackgroundEmerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls (CTR) using diffusion tensor imaging (DTI). MethodsOur sample included 321 adolescents with EOP (mean age: 16.3 {+/-} 1.4 years, 46.4% females) and 265 adolescent CTR (mean age: 16.0 {+/-} 1.7 years, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. ResultsWe found widespread lower FA in EOP compared to CTR, with the largest effect sizes in the superior longitudinal fasciculus (Cohens d = 0.37), posterior corona radiata (d = 0.32), and superior fronto{square}occipital fasciculus (d = 0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. ConclusionUsing the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male patients with early-onset schizophrenia and patients with a shorter duration of illness.