Tract-specific white matter microstructural alterations in subjects with schizophrenia and unaffected first-degree relatives

Abstract

White matter tracts alterations have been reported in schizophrenia (SZ), but whether such abnormalities are associated with the effects of the disorder itself and/or genetic vulnerability remains unclear. Moreover, the specific patterns of different parts of these altered tracts have been less well studied. Thus, diffusion-weighted images were acquired from 38 healthy controls (HCs), 48 schizophrenia patients, and 33 unaffected first-degree relatives of SZs (FDRs). Diffusion properties of the 25 major tracts automatically extracted with probabilistic tractography were calculated and compared among groups. Regarding the peripheral regions of the tracts, significantly higher diffusivity values in the left superior longitudinal fasciculus (SLF) and the left anterior thalamic radiation (ATR) were observed in SZs than in HCs and unaffected FDRs. However, there were no significant differences between HCs and FDRs in these two tracts. While no main effects of group with respect to the core regions of the 25 tracts survived multiple comparisons correction, FDRs had significantly higher diffusivity values in the left medial lemniscus and lower diffusivity values in the middle cerebellar peduncle than HCs and SZs. These findings enhance the understanding of the abnormal patterns in the peripheral and core regions of the tracts in SZs and those at high genetic risk for schizophrenia. Our results suggest that alterations in the peripheral regions of the left SLF and ATR are features of established illness rather than genetic predisposition, which may serve as critical neural substrates for the psychopathology of schizophrenia.

Keywords: Genetic predisposition; Probabilistic tractography; Schizophrenia; Unaffected first-degree relatives; White matter tracts.