To identify the reliable connectivity between causal genes or variants with an abnormality expressed in a certain endophenotype has been viewed as a crucial step in unraveling the etiology of schizophrenia because of the considerable heterogeneity in this disorder.
According to this practical and scientific demand, we aimed to investigate the relationship between seven top-ranked variants in the SZgene database [120-bpTR in DRD4, rs1801028 and rs6277 in DRD2, rs1019385 (T200G) in GRIN2B, rs1800532 in TPH1, rs1801133 (C677T) in MTHFR, rs2619528 (P1765) in DTNBP1] and prepulse inhibition (PPI) and habituation after acoustic stimulus (HAB).
Both PPI and HAB were decreased significantly in patients with schizophrenia. In addition, we observed a significant effect of GRIN2B (human NMDA receptor 2B subunit gene, NR2B) genotype on HAB (P<0.05, not corrected).
Although these findings need to be replicated in other samples, an underlying mechanism of impaired biological reaction may be influenced by NMDA hypofunctioning in schizophrenia.
aDepartment of Neuropsychiatry, Osaka Medical College, Takatsuki
bOzone Hospital, Toyonaka
cGraduate School of Letters, Kansai University
dOsaka Kyoiku University
fAino Hanazono Hospital
gShin-Awaji Hospital, Osaka
hLaboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences, Osaka, Japan
iDepartment of Psychiatry and Behavioral Sciences, Medical Genetics Research Center (MGRC), SUNY Upstate Medical University, USA
Correspondence to Tetsufumi Kanazawa, MD, PhD, Department of Neuropsychiatry, Osaka Medical College, 2-7 Daigaku-machi Takatsuki-City, Osaka 569-0801, Japan
Tel: +81 72 6831221; fax: +81 72 6834810;
Received 19 May 2009 Revised 18 November 2009 Accepted 1 January 2010