title: Oligodendrocyte genes, white matter tract integrity, and cognition in schizophrenia.
abstract: 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.
authors: Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. aristotle_voineskos@camh.net
authors: Aristotle N
authors: AN
authors: Voineskos
authors: Daniel
authors: D
authors: Felsky
authors: Natasa
authors: N
authors: Kovacevic
authors: Arun K
authors: AK
authors: Tiwari
authors: Clement
authors: C
authors: Zai
authors: M Mallar
authors: MM
authors: Chakravarty
authors: Nancy J
authors: NJ
authors: Lobaugh
authors: Martha E
authors: ME
authors: Shenton
authors: Tarek K
authors: TK
authors: Rajji
authors: Dielle
authors: D
authors: Miranda
authors: Bruce G
authors: BG
authors: Pollock
authors: Benoit H
authors: BH
authors: Mulsant
authors: Anthony R
authors: AR
authors: McIntosh
authors: James L
authors: JL
authors: Kennedy
mesh_terms: D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / Q000235:genetics; D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002540:Cerebral Cortex / Q000473:pathology*; D003071:Cognition; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018992:Myelin-Associated Glycoprotein / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020890:Neuregulin-1 / Q000235:genetics; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia; D020641:Polymorphism, Single Nucleotide; D066247:Receptor, ErbB-4; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
chemical_list: D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D051792:Basic Helix-Loop-Helix Proteins; D066246:ErbB Receptors; D018992:Myelin-Associated Glycoprotein; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D000076104:Oligodendrocyte Transcription Factor 2; D066247:Receptor, ErbB-4; C115082:MAG protein, human; C094131:NRG1 protein, human; C405708:OLIG2 protein, human; C587689:ERBB4 protein, human; C571337:CNP protein, human