Tang Y, Pasternak O, Kubicki M, et al. - Researchers examined if a predominantly medication-naive cohort of clinical high-risk individuals experiencing attenuated psychotic symptoms display the presence of cellular and extracellular alterations. They compared 3-T multishell diffusion MRI data of 50 individuals at clinical high risk, of whom 40 were never medicated, vs 50 healthy control individuals who were group-matched for age, gender, and parental socioeconomic status. The clinical high-risk group vs the healthy control group had significantly lower fractional anisotropy of cellular tissue (FA_T). They observed a significant association of lower FA_T in the clinical high-risk group with a decline in Global Assessment of Functioning Scale (GAF) score compared with highest GAF score in the previous 12 months. Findings thus suggest that the clinical high-risk group, especially those who experienced a decline in functioning, cellular but not extracellular alterations occur. These cellular differences reflect an early deficit that may indicate a predisposition to develop attenuated psychotic symptoms. In contrast, they identified no extracellular alterations in this clinical high-risk sample. This indicates a possible value of previously reported extracellular abnormalities as an acute response to psychosis, which plays a more prominent role closer to or at onset of psychosis.