Abstract
Post-mortem studies have demonstrated alterations in superficial white matter (SWM) in schizophrenia patients. Diffusion tensor imaging (DTI) can be used to assess SWM in vivo, and compare SWM fractional anisotropy (FA) in schizophrenia patients vs healthy controls. The assessment of SWM in vivo also provides an opportunity to identify novel neural correlates of cognitive performance, and potential cognitive impairment in schizophrenia patients. Forty-four patients with schizophrenia and 44 matched healthy controls underwent neuroimaging and cognitive protocols. Using an SWM mask and tract-based spatial statistics, differences in SWM-FA were examined between groups. SWM-FA clusters different between groups were then used to predict cognitive performance with multiple linear regression. The relative contribution of SWM fiber subtypes (deep white matter extensions vs U-fibers and intraregional fibers) from significantly different clusters was examined. Compared to controls, patients with schizophrenia had reduced FA in five SWM clusters: the largest a left posterior parieto-occipital cluster, followed by four clusters in the left frontal lobe. SWM-FA in the frontal lobe clusters predicted attention, working memory, and processing speed performance in healthy controls, but not in patients with schizophrenia. The majority of streamlines tracked from these clusters were restricted to U-fibers and intraregional fibers, rather than deep white matter extensions. Our analyses revealed prominent SWM disruption in patients with schizophrenia compared to controls. SWM–cognition relationships shown in healthy individuals were disrupted in patients with schizophrenia. SWM may be an important neurobiological substrate of cognitive performance and a novel cortical treatment target for cognitive deficits in schizophrenia patients.
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Acknowledgements
This work was supported by the Canadian Institutes of Health Research, Ontario Mental Health Foundation, the Brain and Behavior Research Foundation (formerly known as NARSAD), the Centre for Addiction and Mental Health (CAMH), and the CAMH Foundation through the Kimel Family, Koerner New Scientist Award, and Paul E Garfinkel New Investigator Catalyst Award. No sponsor or funder played any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
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Dr Mulsant currently receives research support from Bristol-Myers Squibb (medications for a NIH-funded clinical trial) and Pfizer (medications for a NIH-funded clinical trial). He directly owns stocks of General Electric (<$5000). Within the past 3 years, he has also received some travel support from Roche.
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Nazeri, A., Chakravarty, M., Felsky, D. et al. Alterations of Superficial White Matter in Schizophrenia and Relationship to Cognitive Performance. Neuropsychopharmacol 38, 1954–1962 (2013). https://doi.org/10.1038/npp.2013.93
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DOI: https://doi.org/10.1038/npp.2013.93
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