Water and metabolite transverse T2 relaxation time abnormalities in the white matter in schizophrenia

Abstract

Multiple lines of evidence suggest that microstructural abnormalities in the white matter are important in the pathophysiology of schizophrenia. Diffusion MRI approaches which can provide evidence on tissue structure have been widely used to probe these abnormalities in vivo, but transverse relaxation times (T2) may provide additional insights since they are determined by molecule-microenvironment interactions not revealed by diffusion MRI. T2 of water - located both intra and extracellularly - and N-acetylaspartate (NAA - located intracellularly) reflect related but distinct processes due to their differential localization and interactions with other molecules. In this study, we collected water and NAA T2 data from 16 healthy subjects (HC), and 16 patients with schizophrenia (SZ) at 4 T in a 9 cm(3) voxel in the right prefrontal white matter. The SZ group had longer water but shorter NAA T2 relaxation times when compared with the HC group. This pattern resulted in a statistically significant metabolite×group interaction (F(18,1):4.980, p=0.039). Prolongation of water T2 and shortening of NAA T2 is consistent with an impoverishment of white matter macromolecule structures (including myelin) and abnormal intra-axonal milieu and volume in SZ.