Abstract
Individuals with schizophrenia show a broad range of language impairments, similar to those observed in reading disability (RD). Genetic linkage and association studies of RD have identified a number of candidate RD-genes that are associated with neuronal migration. Some individuals with schizophrenia also show evidence of impaired cortical neuronal migration. We have previously linked RD-related genes with gray matter distributions in healthy controls and schizophrenia. The aim of the current study was to extend these structural findings and to examine links between putative RD-genes and functional connectivity of language-related regions in healthy controls (n = 27) and schizophrenia (n = 28). Parallel independent component analysis (parallel-ICA) was used to examine the relationship between language-related regions extracted from resting-state fMRI and 16 single nucleotide polymorphisms (SNPs) spanning 5 RD-related genes. Parallel-ICA identified four significant fMRI-SNP relationships. A Left Broca-Superior/Inferior Parietal network was related to two KIAA0319 SNPs in controls but not in schizophrenia. For both diagnostic groups, a Broca-Medial Parietal network was related to two DCDC2 SNPs, while a Left Wernicke-Fronto-Occipital network was related to two KIAA0319 SNPs. A Bilateral Wernicke-Fronto-Parietal network was related to one KIAA0319 SNP only in controls. Thus, RD-genes influence functional connectivity in language-related regions, but no RD-gene uniquely affected network function in schizophrenia as compared to controls. This is in contrast with our previous study where RD-genes affected gray matter distribution in some structural networks in schizophrenia but not in controls. Thus these RD-genes may exert a more important influence on structure rather than function of language-related networks in schizophrenia.
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Notes
To avoid confusion, the independent components extracted from the initial ICA using GIFT will be referred to as ‘components’ and the independent components extracted from the parallel-ICA will be referred to as ‘subcomponents’.
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Funding for this study was provided by NIMH Grants R37 MH43775, R01 MH074797, R01 MH077945, to G. Pearlson; funding for J.R. Gruen was provided by NINDS Grant R01 NS 43530.
Yale University has applied for a patent covering markers from and their application to reading disability, which has been licensed to a start-up company founded by J.R. Gruen. All other authors declare that they have no conflicts of interest.
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Jamadar, S., Powers, N.R., Meda, S.A. et al. Genetic influences of resting state fMRI activity in language-related brain regions in healthy controls and schizophrenia patients: a pilot study. Brain Imaging and Behavior 7, 15–27 (2013). https://doi.org/10.1007/s11682-012-9168-1
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DOI: https://doi.org/10.1007/s11682-012-9168-1