Background
Processing speed predicts functional outcome and is a potential endophenotype for schizophrenia. Establishing the neural basis of processing speed impairment may inform the treatment and etiology of schizophrenia. Neuroimaging investigations in healthy subjects have linked processing speed to brain anatomical connectivity. However, the relationship between processing speed impairment and white matter integrity in schizophrenia is unclear.
Methods
Individuals with schizophrenia and healthy subjects underwent diffusion tensor imaging (DTI) and completed a brief neuropsychological assessment that included measures of processing speed, verbal learning, working memory, and executive functioning. Group differences in white matter integrity, inferred from fractional anisotropy (FA), were examined throughout the brain and the hypothesis that processing speed impairment in schizophrenia is mediated by diminished white matter integrity was tested.
Results
White matter integrity of the corpus callosum, cingulum, superior and inferior frontal gyri, and precuneus was reduced in schizophrenia. Average FA in these regions mediated group differences in processing speed, but not other cognitive domains. Diminished white matter integrity in schizophrenia was accounted for, in large part, by individual differences in processing speed.
Conclusions
Cognitive impairment in schizophrenia mediated by reduced white matter integrity. This relationship was strongest for processing speed as deficits in working memory, verbal learning, and executive functioning were not mediated by white integrity. Larger sample sizes may be required to detect more subtle mediation effects in these domains. Interventions that preserve white matter integrity or ameliorate white matter disruption may enhance processing speed and functional outcome in schizophrenia.