Processing speed impairment in schizophrenia is mediated by white matter integrity

Abstract

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.

Reaction Time Is Negatively Associated with Corpus Callosum Area in the Early Stages of CADASIL

“…22 Processing speed has previously been associated with CC A in sporadic forms of SVD and in other brain disorders. 5,[23][24][25] Regarding reports of sporadic forms of SVD, the absence of control subjects did not allow formally disentangling the effects of age from those of SVD in these studies. Moreover, study samples were heterogeneous, including older patients, with a significant proportion probably having associated Alzheimer disease (29% of diagnosed dementia on a 3-year follow-up 6 ).…”

Potassium channel gene associations with joint processing speed and white matter impairments in schizophrenia

“…White matter abnormalities in patients with schizophrenia have been shown to mediate their processing speed deficit (Karbasforoushan et al 2015; Wright et al 2015). Furthermore, processing speed and white matter FA have been found to be phenotypically and genetically correlated (Kochunov et al 2016a).…”

The common genetic influence over processing speed and white matter microstructure: Evidence from the Old Order Amish and Human Connectome Projects

“…Among research findings linking neuroimaging measurements to variance in cognition, the strongest association was observed between white matter FA values and other proxy-measurements of white matter microstructure and fiber organization and the neurocognitive processing speed (Bartzokis, 2004; Bartzokis et al, 2008; Charlton et al, 2009; Karbasforoushan et al, 2015; Kennedy and Raz, 2009; Kochunov et al, 2009a; Kochunov et al, 2009b; Konrad et al, 2009; Muetzel et al, 2008; Schiavone et al, 2009; Vernooij et al, 2009). The overall conclusion of these studies was that white matter microstructure as indexed by FA and other neuroimaging indices are associated with the speed of cerebral information processing (Bartzokis et al, 2010).…”