Ofer Pasternak1, Yingying Tang1,2, Marek Kubicki1, Yogesh Rathi1, Tianhong Zhang2, Zhenying Qian2, William S Stone3, Susan Whitfield-Gabrieli4, Robert W McCarley5, Martha E. Shenton1,5, Jijun Wang2; 11. Brigham and Women’s Hospital, Harvard Medical School, 2Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 3Beth Israel Deaconess Medical Center, Harvard Medical School, 4McGovern Institute for Brain Research, Massachusetts Institute of Technology, 5Veterans Affairs Boston Healthcare System
Purpose: Recent free-water diffusion MRI studies suggest co-occurring extracellular changes, measured by free-water (FW), and microstructural cellular changes, measured by fractional anisotropy of tissue (FAt). The extracellular changes reveal a widespread extent during first psychotic episode, and lower levels during chronic stages of the illness. Cellular changes were limited in the first episode stage, and were more widespread in the chronic stage. These findings led to the hypothesis that FW increases may reflect an acute brain response to psychosis, while FAt may reflect a continuous process of accumulating damage. What is not yet clear is the presentation of these abnormalities prior to the onset of psychosis. Materials and methods: Using 3T diffusion MRI data from the SHARP study we explored white matter alterations in 50 individuals at clinical high risk (CHR) for psychosis who were largely medication-naïve, and 50 matching healthy controls (HC). Results: CHR subjects showed significantly reduced FAt (p=0.020), but no changes in FW (p=0.137). FAt was positively correlated with age (p=0.018) in HC, but not in CHR (p=0.290). Conclusion: Our findings suggest that cellular changes precede the onset of psychosis and may reflect altered neurodevelopmental processes in CHR. As no differences in FW were observed, we predict that FW increases will emerge as an acute response in this CHR sample, closer to the onset of psychosis. We therefore plan to follow-up on these findings in longitudinal analyses to investigate both FW and FAt between individuals who convert to psychosis compared to those who do not convert.
