Effect of metabotropic glutamate receptor-3 variants on prefrontal brain activity in schizophrenia: An imaging genetics study using multi-channel near-infrared spectroscopy.
BACKGROUND
The glutamatergic system is essential for learning and memory through its crucial role in neural development and synaptic plasticity. Genes associated with the glutamatergic system, including metabotropic glutamate receptor (mGluR or GRM) genes, have been implicated in the pathophysiology of schizophrenia. Few studies, however, have investigated a relationship between polymorphism of glutamate-related genes and cortical function in vivo in patients with schizophrenia. We thus explored an association between genetic variations in GRM3 and brain activation driven by a cognitive task in the prefrontal cortex in patients with schizophrenia.


METHODS
Thirty-one outpatients with schizophrenia and 48 healthy controls participated in this study. We measured four candidate single nucleotide polymorphisms (rs274622, rs2299225, rs1468412, and rs6465084) of GRM3, and activity in the prefrontal and temporal cortices during a category version of a verbal fluency task, using a 52-channel near-infrared spectroscopy instrument.


CONCLUSIONS
The rs274622 C carriers with schizophrenia were associated with significantly smaller prefrontal activation than patients with TT genotype. This between-genotype difference tended to be confined to the patient group. GRM3 polymorphisms are associated with prefrontal activation during cognitive task in schizophrenia.
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Akihide
A
Kinoshita
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London SE5 8AF, UK.
Ryu
R
Takizawa
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; Office for Mental Health Support, Division for Counseling and Support, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Shinsuke
S
Koike
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Yoshihiro
Y
Satomura
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; Application Development Office, Hitachi Medical Corporation, Kashiwa City, Chiba 277-0804, Japan.
Shingo
S
Kawasaki
Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Yuki
Y
Kawakubo
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Kohei
K
Marumo
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; Department of Psychiatry, Teikyo University School of Medicine, Itabashi-ku, Tokyo 173-8605, Japan.
Mamoru
M
Tochigi
Department of Physical and Health Education, Graduate School of Education, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Tsukasa
T
Sasaki
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Yukika
Y
Nishimura
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: kasaik-tky@umin.net.
Kiyoto
K
Kasai
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003071:Cognition / Q000502:physiology*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000378:metabolism*; D018091:Receptors, AMPA / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D019265:Spectroscopy, Near-Infrared
D014150:Antipsychotic Agents; D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3
Glutamatergic system; Imaging genetics; Intermediate phenotype; Verbal fluency task