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
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.
Available from: Walter Heinrichs
- "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. "
[Show abstract] [Hide abstract]
ABSTRACT: The validity and significance of normal range neurocognition in schizophrenia remain unclear and controversial. We assessed whether normal range patients and controls demonstrate evidence of decline relative to premorbid ability and differ in performance profiles across measures, including those external to the normality criterion. In addition, we compared below normal range healthy control participants with patients at the same ability level. Performance normality was defined as a MATRICS Consensus Cognitive Battery (MCCB) composite T score between 40 and 60. Patients (n=17) and controls (n=24) meeting the criterion were compared on MCCB domain scores and on independent measures of reading ability, probabilistic and social reasoning. Patients (n=19) and controls (n=20) scoring below 40 on the MCCB composite were compared on the same set of measures. Cognitively normal range patients and controls did not differ on estimated premorbid ability or decline and differed only on the Processing Speed domain of the MCCB. Performance did not differ across other domains or on social and probabilistic reasoning tasks. Cognitively below normal range patients and controls showed marked discrepancies between premorbid and current ability, but there were no group differences. In addition, below normal range groups did not differ on any MCCB domain score or in terms of external cognitive measures. Cognitively normal range schizophrenia patients may be largely indistinguishable from normal range controls, with the exception of processing speed performance. More typical schizophrenia patients below the normal range may be indistinguishable from low-performing controls even in terms of processing speed.
[Show abstract] [Hide abstract]
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.
Available from: Thomas R. Coyle
[Show abstract] [Hide abstract]
ABSTRACT: Speed with which brain performs information processing influences overall cognition and is dependent on the white matter fibers. To understand genetic influences on processing speed and white matter FA, we assessed processing speed and diffusion imaging fractional anisotropy (FA) in related individuals from two populations. Discovery analyses were performed in 146 individuals from large Old Order Amish (OOA) families and findings were replicated in 485 twins and siblings of the Human Connectome Project (HCP). The heritability of processing speed was h(2)=43% and 49% (both p<0.005), while the heritability of whole brain FA was h(2)=87% and 88% (both p<0.001), in the OOA and HCP, respectively. Whole brain FA was significantly correlated with processing speed in the two cohorts. Quantitative genetic analysis demonstrated a significant degree to which common genes influenced joint variation in FA and brain processing speed. These estimates suggested common sets of genes influencing variation in both phenotypes, consistent with the idea that common genetic variations contributing to white matter may also support their associated cognitive behavior.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.