Processing speed impairment in schizophrenia is mediated by white matter integrity

Department of Psychiatry, Vanderbilt University, Нашвилл, Michigan, United States
Psychological Medicine (Impact Factor: 5.94). 05/2014; 45(01):1-12. DOI: 10.1017/S0033291714001111
Source: PubMed


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 (WM) integrity in schizophrenia is unclear.

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 WM integrity, inferred from fractional anisotropy (FA), were examined throughout the brain and the hypothesis that processing speed impairment in schizophrenia is mediated by diminished WM integrity was tested.

WM 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 in other cognitive domains. Diminished WM integrity in schizophrenia was accounted for, in large part, by individual differences in processing speed.

Cognitive impairment in schizophrenia was mediated by reduced WM integrity. This relationship was strongest for processing speed because deficits in working memory, verbal learning and executive functioning were not mediated by WM integrity. Larger sample sizes may be required to detect more subtle mediation effects in these domains. Interventions that preserve WM integrity or ameliorate WM disruption may enhance processing speed and functional outcome in schizophrenia.

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    • "Nevertheless, this does not account for the special sensitivity of processing speed tasks at higher joint ability levels. Recent evidence suggests that these tasks associate specifically with white matter integrity (Karbasforoushan et al., 2015). Therefore, a further possibility is that the general cognitive deficit observed across multiple domains in most schizophrenia patients is absent or virtually absent in a minority, but with reduced connectivity and hence slowed processing persisting as a residual weakness. "
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