Schizophrenia Bulletin Advance Access published online on November 14, 2008
Schizophrenia Bulletin, doi:10.1093/schbul/sbn160
Supportive evidence for reduced expression of GNB1L in schizophrenia
2 Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan
3 CREST, Japan Science and Technology Agency, Kawaguchi-shi, Saitama 332-0012, Japan
4 Department of Schizophrenia Research, Tokyo Institute of Psychiatry, Tokyo 156-8585, Japan
5 Tokyo Metropolitan Matsuzawa Hospital, Department of Psychiatry, Tokyo 156-0057, Japan
6 Seiwa Hospital, Institute of Neuropsychiatry, Tokyo 162-0851, Japan
7 Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
8 Department of Psychiatry, Nagoya University, School of Medicine, Nagoya 466-8550, Aichi, Japan
9 Department of Neuropsychiatry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
10 National Center of Neurology and Psychiatry, Tokyo 187-8551, Japan
11 Health Service Center, University of Tokyo, Tokyo 113-0033, Japan
12 Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
13 Brain Research Institute, Niigata University, Niigata 951-8585, Japan, Department of Pathology
14 Department of Pathological Neuroscience, Brain Research Institute, Niigta University, Niigata 951-8585, Japan
15 Department of Pathology, Brain Research Institute, Niigta University, Niigata 951-8585, Japan
1 To whom correspondence should be addressed; Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan; tel: +81-29-853-3352, fax: +81-29-853-3333, e-mail: hishigur{at}md.tsukuba.ac.jp
Background: Chromosome 22q11 deletion syndrome (22q11DS) increases the risk of development of schizophrenia more than 10 times compared with that of the general population, indicating that haploinsufficiency of a subset of the more than 20 genes contained in the 22q11DS region could increase the risk of schizophrenia. In the present study, we screened for genes located in the 22q11DS region that are expressed at lower levels in postmortem prefrontal cortex of patients with schizophrenia than in those of controls. Methods: Gene expression was screened by Illumina Human-6 Expression BeadChip arrays and confirmed by real-time reverse transcription-polymerase chain reaction assays and Western blot analysis. Results: Expression of GNB1L was lower in patients with schizophrenia than in control subjects in both Australian (10 schizophrenia cases and 10 controls) and Japanese (43 schizophrenia cases and 11 controls) brain samples. TBX1 could not be evaluated due to its low expression levels. Expression levels of the other genes were not significantly lower in patients with schizophrenia than in control subjects. Association analysis of tag single-nucleotide polymorphisms in the GNB1L gene region did not confirm excess homozygosity in 1918 Japanese schizophrenia cases and 1909 Japanese controls. Haloperidol treatment for 50 weeks increased Gnb1l gene expression in prefrontal cortex of mice. Conclusions: Taken together with the impaired prepulse inhibition observed in heterozygous Gnb1l knockout mice reported by the previous study, the present findings support assertions that GNB1L is one of the genes in the 22q11DS region responsible for increasing the risk of schizophrenia.
Keywords: 22q11DS / haloperidol / prefrontal cortex / postmortem brain