The association of genotypic combination of the DRD3 and BDNF polymorphisms on the adhesio interthalamica and medial temporal lobe structures.
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.
Takahashi
Tsutomu
T
Department of Neuropsychiatry, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Suzuki
Michio
M
Tsunoda
Masahiko
M
Kawamura
Yukiko
Y
Takahashi
Nagahide
N
Maeno
Nobuhisa
N
Kawasaki
Yasuhiro
Y
Zhou
Shi-Yu
SY
Hagino
Hirofumi
H
Niu
Lisha
L
Tsuneki
Hiroshi
H
Kobayashi
Soushi
S
Sasaoka
Toshiyasu
T
Seto
Hikaru
H
Kurachi
Masayoshi
M
Ozaki
Norio
N
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
D019208:Brain-Derived Neurotrophic Factor; D050637:Receptors, Dopamine D3; D012694:Serine; D008715:Methionine; D014633:Valine; D005998:Glycine