Information processing speed mediates the relationship between white matter and general intelligence in schizophrenia

• We examined whether white matter microstructure was associated with general intelligence through information processing speed in schizophrenia.
• Fractional anisotropy (FA) and mean diffusivity (MD) were extracted from 46 white matter regionsusing Tract-based Spatial Statistics.
• General factors were obtained from FA and MD and a battery of cognitive tests using principal component analysis.
• There was a significant association between general intelligence and the general factor for FA which was mediated by information processing speed.
• We suggest a plausible model of structure-function where white matter may provide a neuroanatomical substrate for general intelligence supported partially by information processing speed.

Several authors have proposed that schizophrenia is the result of impaired connectivity between specific brain regions rather than differences in local brain activity. White matter abnormalities have been suggested as the anatomical substrate for this dysconnectivity hypothesis. Information processing speed may act as a key cognitive resource facilitating higher order cognition by allowing multiple cognitive processes to be simultaneously available. However, there is a lack of established associations between these variables in schizophrenia. We hypothesised that the relationship between white matter and general intelligence would be mediated by processing speed. White matter water diffusion parameters were studied using Tract-based Spatial Statistics and computed within 46 regions-of-interest (ROI). Principal component analysis was conducted on these white matter ROI for fractional anisotropy (FA) and mean diffusivity, and on neurocognitive subtests to extract general factors of white mater structure (gFA, gMD), general intelligence (g) and processing speed (gspeed). There was a positive correlation between g and gFA (r= 0.67, p =0.001) that was partially and significantly mediated by gspeed (56.22% CI: 0.10–0.62). These findings suggest a plausible model of structure-function relations in schizophrenia, whereby white matter structure may provide a neuroanatomical substrate for general intelligence, which is partly supported by speed of information processing.