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Genetic influences of resting state fMRI activity in language-related brain regions in healthy controls and schizophrenia patients: a pilot study

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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

  1. 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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Acknowledgements

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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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Authors and Affiliations

  1. Olin Neuropsychiatry Research Center, Institute of Living, 200 Retreat Ave, Hartford, CT, 06106, USA

    Sharna Jamadar, Shashwath A. Meda & Godfrey D. Pearlson

  2. Department of Genetics, Yale University, New Haven, CT, USA

    Natalie R. Powers, Joel Gelernter & Jeffrey R. Gruen

  3. Department of Psychiatry, Yale University, New Haven, CT, USA

    Vince D. Calhoun, Joel Gelernter & Godfrey D. Pearlson

  4. Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA

    Vince D. Calhoun

  5. The Mind Research Network, Albuquerque, NM, USA

    Vince D. Calhoun

  6. Department of Pediatrics, Yale University, New Haven, CT, USA

    Jeffrey R. Gruen

  7. Department of Neurobiology, Yale University, New Haven, CT, USA

    Godfrey D. Pearlson

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  1. Sharna Jamadar
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  2. Natalie R. Powers
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  3. Shashwath A. Meda
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Correspondence to Sharna Jamadar.

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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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