title: Glutamate receptor δ 1 (GRID1) genetic variation and brain structure in schizophrenia.
abstract: Common genetic variation in the promoter region of the glutamate receptor delta 1 (GRID1) gene has recently been shown to confer increased risk for schizophrenia in several independent large samples. We analysed high-resolution magnetic resonance imaging (MRI) data from 62 patients with schizophrenia and 54 healthy controls using voxel-based morphometry (VBM) to assess the effect of single nucleotide polymorphism rs3814614 (located in the GRID1 promoter region), of which the T allele was identified as a risk factor in a previous association study. There were no effects of genotype or group × genotype interactions on total brain grey matter or white matter, but on regional grey matter. In healthy subjects, we identified a significant effect of rs3814614 genotype in the anterior thalamus (bilaterally), superior prefrontal cortex, and orbitofrontal cortex - in all cases with the homozygous risk genotype TT resulting in higher grey matter density. We did not find this association within the schizophrenia sample, where rs3814614 variation was only associated with grey matter reduction in TT homozygous subjects in medial parietal cortex and increased grey matter in right medial cerebellum. For white matter, we did not find significant genotype effects in healthy controls, and only minor effects within schizophrenia patients in the posterior temporal lobe white matter. Our data indicate that GRID1 rs3814614 genotype is related to grey matter variation in prefrontal and anterior thalamic brain areas in healthy subjects, but not in patients indicating a potential role of this schizophrenia candidate gene in thalamo-cortical functioning.
authors.affiliation: Department of Psychiatry and Psychotherapy, Jena University Hospital, Philosophenweg 3, 07743 Jena, Germany. igor.nenadic@uni-jena.de
authors.forename: Igor
authors.initials: I
authors.lastname: Nenadic
authors.forename: Raka
authors.initials: R
authors.lastname: Maitra
authors.forename: Sigrid
authors.initials: S
authors.lastname: Scherpiet
authors.forename: Christian
authors.initials: C
authors.lastname: Gaser
authors.forename: C Christoph
authors.initials: CC
authors.lastname: Schultz
authors.forename: Claudia
authors.initials: C
authors.lastname: Schachtzabel
authors.forename: Stefan
authors.initials: S
authors.lastname: Smesny
authors.forename: Jürgen R
authors.initials: JR
authors.lastname: Reichenbach
authors.forename: Jens
authors.initials: J
authors.lastname: Treutlein
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Mühleisen
authors.forename: Thomas
authors.initials: T
authors.lastname: Deufel
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Heinrich
authors.initials: H
authors.lastname: Sauer
authors.forename: Ralf G M
authors.initials: RG
authors.lastname: Schlösser
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology; D017470:Receptors, Glutamate / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013788:Thalamus / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D017470:Receptors, Glutamate; C108929:glutamate receptor delta 1