Developmental abnormalities in brain white matter in prodromes with 22q11.2 Deletion Syndrome: A tract based spatial statistics study

Abstract

Background Schizophrenia is believed to be a neurodevelopmental disorder, and might originate earlier than the first symptoms present clinically. Subjects with 22q11.2 Deletion Syndrome (22q11DS) represent a promising cohort to explore biomarkers of schizophrenia prior to symptoms onset, as there is a 30% incidence of schizophrenia in adult life. In this study, we explored whether changes in whole brain white matter are present in adolescents with 22q11.2DS and in prodromes (22q11DS subjects with a high score on Brief Psychiatric Rating Scale).

Methods Diffusion Magnetic Resonance Images (dMRI) of the brain white matter were acquired from 47 controls and 50 subjects with 22q11DS, including 9 prodromes (mean age 18 ± 2 years). Whole brain white matter was analyzed using the Tract Based Spatial Statistics (TBSS) method. dMRI measures, such as Fractional Anisotropy (FA), Mean Diffusivity (MD), Axial Diffusivity (AD) and Radial Diffusivity (RD) were compared between the groups.

Results When controls were compared to all the subjects with 22q11DS, statistically significant reductions in MD, AD and RD were found in the 22q11DS group. The changes were localized to the corpus callosum (CC) and the long association fiber tracts. When the 22q11DS group was split, the prodromes showed statistically significant reductions in MD, AD and RD in the CC and Superior Longitudinal Fasciculus (SLF).

Discussion Changes in white matter were observed in individuals with 22q11.2DS, which could be interpreted as developmental and axonal abnormalities. The changes found in the prodromes point to even more severe developmental abnormalities. The changes in dMRI indices, reported here, differ from those observed in chronic schizophrenia. In chronic schizophrenia reduced FA and increased RD are being interpreted as abnormalities of the myelin. We hope that studying these prodromes will allow us to develop a more complete understanding of the changes in brain white matter that lead to schizophrenia.