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Oligodendrocyte Genes, White Matter Tract Integrity, and Cognition in Schizophrenia

Institution:	1Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. 2Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. 3Rotman Research Institute, Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada. 4Brigham and Women's Hospital and Brockton VA Healthcare System, Harvard Medical School, Boston/Brockton, MA, USA. 5Department of Psychiatry, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada. 6Neurogenetics Section, Neuroscience Department, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Publisher:	HighWire Press
Publication Date:	Jul-2012
Journal:	Cereb Cortex
Citation:	Cereb Cortex. 2012 Jul 6.
PubMed ID:	22772651
Keywords:	cognition, DTI, genetics, oligodendrocytes, white matter
Appears in Collections:	PNL
Generated Citation:	Voineskos A.N., Felsky D., Kovacevic N., Tiwari A.K., Zai C., Chakravarty M.M., Lobaugh N.J., Shenton M.E., Rajji T.K., Miranda D., Pollock B.G., Mulsant B.H., McIntosh A.R., Kennedy J.L. Oligodendrocyte Genes, White Matter Tract Integrity, and Cognition in Schizophrenia. Cereb Cortex. 2012 Jul 6. PMID: 22772651.
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Oligodendrocyte genes and white matter tracts have been implicated in the pathophysiology of schizophrenia and may play an important etiopathogenic role in cognitive dysfunction in schizophrenia. The objective of the present study in 60 chronic schizophrenia patients individually matched to 60 healthy controls was to determine whether 1) white matter tract integrity influences cognitive performance, 2) oligodendrocyte gene variants influence white matter tract integrity and cognitive performance, and 3) effects of oligodendrocyte gene variants on cognitive performance are mediated via white matter tract integrity. We used the partial least-squares multivariate approach to ascertain relationships among oligodendrocyte gene variants, integrity of cortico-cortical and subcortico-cortical white matter tracts, and cognitive performance. Robust relationships among oligodendrocyte gene variants, white matter tract integrity, and cognitive performance were found in both patients and controls. We also showed that effects of gene variants on cognitive performance were mediated by the integrity of white matter tracts. Our results were strengthened by bioinformatic analyses of gene variant function. To our knowledge, this is the first study that has brought together these lines of investigation in the same population and highlights the importance of the oligodendrocyte/white matter pathway in schizophrenia, particularly as it pertains to cognitive function.