title: Association of GRM3 polymorphism with white matter integrity in schizophrenia.
abstract: BACKGROUND
  While the functional disconnectivity hypothesis of schizophrenia has received considerable attention, fewer studies have investigated the contribution of genotype to structural connectivity between brain regions either in schizophrenia patients or in healthy controls. In this study, we obtained diffusion tensor imaging (DTI) data and genome-wide single nucleotide polymorphism (SNP) data from 74 cases and 87 age- and gender-matched controls.
  
  
  METHODS
  We used independent component analysis (ICA) to analyze fractional anisotropy (FA) values and correlated FA values with 121 SNPs in genes associated with myelination and/or schizophrenia risk.
  
  
  RESULTS
  Using ICA, we identified 6 maximally independent components in which the majority of the voxels corresponded to known white matter (WM) tracts. Among these WM-enriched components, two had FA values that were significantly decreased in patients. In addition, we examined the relationship between FA values and genotype and found that a SNP located in the intronic region of the metabotropic glutamate receptor 3 gene, GRM3, shows a significant correlation with FA values in a component containing tracts from the cortico-cerebellar-thalamic-cortical circuit of patients but not controls.
  
  
  CONCLUSIONS
  Our findings strengthen the evidence for an association between GRM3 genotype and schizophrenia and suggest a role for glutamate neurotransmission in the establishment and maintenance of myelinated fibers.
authors.affiliation: Department of Neuroscience, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Mounce
authors.affiliation: The Mind Research Network (MRN) and Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, USA. Electronic address: lluo@salud.unm.edu.
authors.forename: Li
authors.initials: L
authors.lastname: Luo
authors.affiliation: The Mind Research Network (MRN) and Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, USA.
authors.forename: Arvind
authors.initials: A
authors.lastname: Caprihan
authors.affiliation: The Mind Research Network (MRN) and Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, USA.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neuroscience, University of New Mexico, Albuquerque, NM, USA. Electronic address: NBizzozero@salud.unm.edu.
authors.forename: Nora I
authors.initials: NI
authors.lastname: Perrone-Bizzozero
authors.affiliation: Department of Neuroscience, University of New Mexico, Albuquerque, NM, USA; The Mind Research Network (MRN) and Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, USA; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA. Electronic address: vcalhoun@mrn.org.
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
chemical_list: D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3
keywords: Cortico–cerebellar–thalamic–cortical circuit; DTI; GRM3; Independent component analysis; Schizophrenia; mGluR3