title: The association of genotypic combination of the DRD3 and BDNF polymorphisms on the adhesio interthalamica and medial temporal lobe structures.
abstract: Abnormal neurodevelopment in midline structures such as the adhesio interthalamica (AI), as well as in the medial temporal lobe structures has been implicated in schizophrenia, while its genetic mechanism is unknown. This magnetic resonance imaging study investigated the effect of the genotypic combination of the dopamine D3 receptor (DRD3) Ser9Gly and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms on the AI length and volumetric measures of the medial temporal lobe structures (amygdala, hippocampus, and parahippocampal gyrus) in 33 schizophrenia patients and 29 healthy controls. The subjects with a combination of the Ser/Ser genotype of DRD3 and Met-containing genotypes of BDNF (high-risk combination) had a shorter AI than those without it in the healthy controls, but not in the schizophrenia patients. The subjects carrying the high-risk combination had a smaller posterior hippocampus than those without it for both diagnostic groups. These genotypic combination effects on brain morphology were not explained by the independent effect of each polymorphism. These findings suggest the effect of gene-gene interaction between the DRD3 and BDNF variations on brain morphology in midline and medial temporal lobe structures, but do not support its specific role in the pathogenesis of schizophrenia.
authors.affiliation: Department of Neuropsychiatry, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takahashi
authors.forename: Michio
authors.initials: M
authors.lastname: Suzuki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tsunoda
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Nagahide
authors.initials: N
authors.lastname: Takahashi
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Maeno
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Shi-Yu
authors.initials: SY
authors.lastname: Zhou
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hagino
authors.forename: Lisha
authors.initials: L
authors.lastname: Niu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuneki
authors.forename: Soushi
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Sasaoka
authors.forename: Hikaru
authors.initials: H
authors.lastname: Seto
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kurachi
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
mesh_terms: D000293:Adolescent; D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004292:Dominance, Cerebral; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008715:Methionine / Q000235:genetics; D011110:Polymorphism, Genetic; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*; D012694:Serine / Q000235:genetics; D013702:Temporal Lobe / Q000002:abnormalities* / Q000473:pathology; D013788:Thalamus / Q000002:abnormalities* / Q000473:pathology; D014633:Valine / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D050637:Receptors, Dopamine D3; D012694:Serine; D008715:Methionine; D014633:Valine; D005998:Glycine