Processing speed impairment in schizophrenia is mediated by white matter integrity
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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ABSTRACT: Speed of processing is impaired in schizophrenia but intact in schizotypal college students. In view of this disparity, we investigated whether deficient processing speed was associated with schizotypy in adults from the general community. Data were drawn from the Western Australian Family Study of Schizophrenia, including 216 (non-clinical) adults from the general community, and a reference group with schizophrenia spectrum disorder (N=224). Schizotypal traits were assessed with the Schizotypal Personality Questionnaire, whilst processing speed was assessed with a digit-symbol coding task. Community controls had significantly higher digit symbol coding scores than patients with psychosis. However, both correlational and hierarchical regression analysis indicated a lack of association between Cognitive-perceptual, Interpersonal or Disorganized schizotypy traits and digit symbol coding performance. Relative to Australian norms there was also no evidence of a non-linear decline in coding in high schizotypes in young, mature or senior age groups. The results show that speed of information processing is unimpaired in high schizotypes from the general community. The possibility that intact processing speed in at-risk groups confers protection to psychosis onset is discussed. Assessing the trajectory of processing speed throughout development may provide a useful clinical screening tool to distinguish those at heightened risk of developing psychosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.Psychiatry Research 06/2015; 228(3). DOI:10.1016/j.psychres.2015.06.003 · 2.47 Impact Factor