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Physiogenomic Analysis of Localized fMRI Brain Activity in Schizophrenia

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Abstract

The search for genetic factors associated with disease is complicated by the complexity of the biological pathways linking genotype and phenotype. This analytical complexity is particularly concerning in diseases historically lacking reliable diagnostic biological markers, such as schizophrenia and other mental disorders. We investigate the use of functional magnetic resonance imaging (fMRI) as an intermediate phenotype (endophenotype) to identify physiogenomic associations to schizophrenia. We screened 99 subjects, 30 subjects diagnosed with schizophrenia, 13 unaffected relatives of schizophrenia patients, and 56 unrelated controls, for gene polymorphisms associated with fMRI activation patterns at two locations in temporal and frontal lobes previously implied in schizophrenia. A total of 22 single nucleotide polymorphisms (SNPs) in 15 genes from the dopamine and serotonin neurotransmission pathways were genotyped in all subjects. We identified three SNPs in genes that are significantly associated with fMRI activity. SNPs of the dopamine beta-hydroxylase (DBH) gene and of the dopamine receptor D4 (DRD4) were associated with activity in the temporal and frontal lobes, respectively. One SNP of serotonin-3A receptor (HTR3A) was associated with temporal lobe activity. The results of this study support the physiogenomic analysis of neuroimaging data to discover associations between genotype and disease-related phenotypes.

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Acknowledgments

This work was supported in part by grants from the National Institutes of Health, under RO1 grants MH60504, MH43775, MH52886, EB000840, EB005846, and an NIMH MERIT award (to GP), as well as SBIR R43 grant MH075481 (to GR).

Financial Disclosures

Dr. Windemuth, Dr. Ruaño, and Mr. Kocherla report financial interest in Genomas Inc. in the form of salary, stock, and stock options. Dr. Calhoun and Dr. Pearlson report no financial interests in companies or potential conflicts of interest.

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Authors and Affiliations

  1. Genomas, Inc., Hartford, CT, 06106, USA

    Andreas Windemuth, Mohan Kocherla & Gualberto Ruaño

  2. Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT, 06106, USA

    Vince D. Calhoun, Godfrey D. Pearlson & Kanchana Jagannathan

  3. Yale University School of Medicine, New Haven, CT, 06520, USA

    Vince D. Calhoun & Godfrey D. Pearlson

  4. The MIND Institute, Albuquerque, NM, 87131, USA

    Vince D. Calhoun

  5. Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, 87131, USA

    Vince D. Calhoun

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  3. Godfrey D. Pearlson
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  4. Mohan Kocherla
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  5. Kanchana Jagannathan
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  6. Gualberto Ruaño
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Correspondence to Andreas Windemuth.

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Windemuth, A., Calhoun, V.D., Pearlson, G.D. et al. Physiogenomic Analysis of Localized fMRI Brain Activity in Schizophrenia. Ann Biomed Eng 36, 877–888 (2008). https://doi.org/10.1007/s10439-008-9475-2

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  • DOI: https://doi.org/10.1007/s10439-008-9475-2

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