Article

Alterations of Superficial White Matter in Schizophrenia and Relationship to Cognitive Performance

Kimel Family Translational Imaging-Genetics Laboratory.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology (Impact Factor: 7.83). 04/2013; 38(10). DOI: 10.1038/npp.2013.93
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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. 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 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.Neuropsychopharmacology accepted article preview online, 16 April 2013; doi:10.1038/npp.2013.93.

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    • "ocytes to oligodendrocytes , as oligo - dendrocytes are involved in myelination . The oligodendro - cyte changes thought to be accompanied by altered gene expression and abnormal myelination ( Uranova et al . , 2011 ) are a possible source of the white matter alterations detected by DTI studies ( Whitford et al . , 2011 ; Nakamura et al . , 2012 ; Nazeri et al . , 2013 ) . Since oligodendrocytes are known to express excitatory glutamate receptors , the putative deficits in glutamatergic neurotransmission in schizophrenia ( see Harrison and Weinberger , 2005 for review ) may reflect oligodendroglial changes . Disruption of the glutamate – glutamine cycle , or changes in perineuronal nets in late develo"
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    • "Diffusion tensor imaging (DTI) is widely used for quantification of cerebral white matter (WM) integrity in disorders that affect cerebral connectivity including schizophrenia (Friedman et al., 2008; Jones et al., 2006; Kanaan et al., 2005; Kochunov et al., 2013; Mori et al., 2007; Nazeri et al., 2013) and other psychiatric and neurological disorders (Allan et al., 2011; Blood et al., 2011; Kanaan et al., 2005; Kieseppa et al., 2011; Korgaonkar et al., 2011; White et al., 2008; Zhang et al., 2012). DTI-derived fractional anisotropy (FA) of water diffusion (Basser and Pierpaoli, 1996; Kochunov et al., 2007; Pfefferbaum et al., 2000; Song et al., 2003, 2005) has emerged as one of the more sensitive imaging biomarkers in schizophrenia research (Friedman et al., 2008; Glahn et al., 2011; Mori et al., 2007). "
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