1. ¹Division of Psychiatry and Neurology, Department of Environmental Health and Safety, Faculty of Medical Sciences, Graduate School of Medicine, Kobe University, 7-5-1 Kusunoki-cho Chuo-Ku, Kobe 650-0017, Japan
2. ²Department of Psychiatry and Neurology, Kobe General City Hospital, Kobe, Japan
3. ³Division of Molecular Medicine & Medical Genetics, International Center for Medical Research (ICMR), Graduate School of Medicine, Kobe University, Kobe, Japan
4. ⁴Division of Legal Medicine, Department of Environmental Health and Safety, Faculty of Medical Sciences, Graduate School of Medicine, Kobe University, Kobe, Japan
5. ⁵Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan

Correspondence: Osamu Shirakawa, Division of Psychiatry and Neurology, Department of Environmental Health and Safety, Faculty of Medical Sciences, Graduate School of Medicine, Kobe University, 7-5-1 Kusunoki-cho Chuo-Ku, Kobe 650-0017, Japan. Fax: +81-78-3826079. E-mail: sirakawa@kobe-u.ac.jp

Received 9 December 2004; Accepted 14 February 2005; Published online 19 April 2005.

Abstract

Genetic factors have been suggested to be involved in suicide. Although some genetic factors, such as serotonergic transduction, have been associated with suicide, the results are inconsistent. There is a possibility that various signaling anomalies are involved in the biological vulnerability to suicide. We carried out a genome-wide gene-expression study in the brains of suicide victims using DNA microarrays;14-3-3 , which is related to neurogenesis, was one of the genes upregulated in the brains of suicide victims in the microarray analysis. This was confirmed by Western blot analysis. To examine the possibility of the involvement of 14-3-3 in the pathogenesis of suicide, we investigated the association of the 14-3-3 gene and completed suicide. We used three high-frequency SNPs (rs1532976, rs3752826, and rs9393) and found a significant association of two alleles (rs1532976 and rs3752826) with completed suicide (p < 0.05). Moreover, the distribution of haplotype revealed a more significant difference between completed suicide and controls (p=0.0005). This finding suggests that 14-3-3 is a potential suicide susceptibility gene and implies that dysregulation of neurogenesis may be involved in suicide.