A longitudinal study investigating sub-threshold symptoms and white matter changes in individuals with an 'at risk...

Evidence supports disruption in white matter (WM) connectivity in established schizophrenia, however, it is unclear when these abnormalities occur during the course of illness and if they are progressive. Here we investigated whether WM abnormalities predate illness onset by examining a group of individuals with an 'at risk mental state' (ARMS) and assess whether there is evidence of progressive change. We hypothesized that WM abnormalities are associated with symptom change.

Sixteen healthy controls and 41 ARMS subjects at baseline underwent Diffusion Tensor Imaging (DTI). Sub-threshold positive symptoms were measured using the Scale of Prodromal Symptoms (SOPS). Imaging and symptoms were re-administered in the ARMS group after one year (52weeks). Fractional anisotropy (FA) value differences between ARMS and control groups at baseline were localized using the method of Tract-Based Spatial Statistics (TBSS).

At baseline, FA was significantly reduced in a sub-region of the corpus callosum (CC) in the ARMS group as a whole compared to controls. This reduction was also found in the 34 individuals who did not transition (ARMS-N) during the one-year follow-up. However, the ARMS-N group showed a significant improvement in sub-threshold positive symptoms at follow-up, which was correlated with an increase in FA in the same CC region (r=-0.664, p<0.001).

There was a significant FA reduction in the CC in individuals at high risk for psychosis regardless of transition status at one year. This suggests that WM abnormalities in the CC may represent a biological vulnerability to psychosis. Improvement in sub-threshold positive symptoms was associated with improvement in measures of WM integrity in the CC. This may suggest that neurobiological 'resilience' is associated with improved outcomes, although this notion requires future study.