Tang Y, et al. - Given the significance of the identification of brain abnormalities in clinical high-risk populations before the onset of psychosis for tracking pathological pathways and for identifying possible intervention strategies that may impede or prevent the onset of psychotic disorders, researchers examined whether a predominantly medication-naive cohort of clinical high-risk individuals experiencing attenuated psychotic symptoms display cellular and extracellular alterations. They performed 3-T multishell diffusion MRI on 50 individuals at clinical high risk, of whom 40 were never medicated, and 50 healthy control subjects for determining free-water imaging white matter measures, including fractional anisotropy of cellular tissue (FA_T) and the volume fraction of extracellular free water (FW) The clinical high-risk group vs the healthy control group showed significantly lower FA_T but had no statistically significant FW alterations. The clinical high-risk group displayed significant association of lower FA_T with a decline in Global Assessment of Functioning Scale (GAF) score compared with highest GAF score in the previous 12 months. As this clinical high-risk sample displayed no extracellular alterations, it seems that previously reported extracellular abnormalities may due to an acute response to psychosis, which plays a more prominent role closer to or at onset of psychosis.