A gene expression and protomi study provide further evidence for the involvement of spermidine/spermine N (1)-acetyltransferase (SSAT1) in suicide and suggests new biological determinants of suicidal behavior in bipolar disorder patients

摘要: Suicide is strongly associated with Major Affective Disorders with a risk for completed suicide 6 to 15 times higher in patients compared to the general population. Lithium is to date the most effective treatment for bipolar disorder (BD) with a well established protective effect against suicide. However, the mechanisms responsible for these clinical effects remain unclear. So far, several studies attempted to identify biological markers and genes involved in suicide. A gene expression microarray study performed using postmortem brain tissue by Sequeira et al. (2006) reported a significant reduction in expression of the gene encoding the enzyme spermidine/spermine N1-acetyltransferase 1 (SSAT1) in suicide completers with and without depression compared to controls. This result has been replicated by others. To confirm and extend these findings, we measured SSAT1 gene expression levels in lymphoblastoid cell lines (LCLs) from two populations (Sardinian, n = 41 and Canadian, n = 24) of BD subjects characterized for suicidal behaviour and healthy controls. In order to test the effect of lithium on SSAT1, each LCL was divided into two lines cultured for 7 days in media with and without LiCl (1.0 mmol/l). SSAT1 expression was significantly increased by lithium in LCLs from controls (p< 0.001) and in subjects with low (p < 0.001) and high (p < 0.001) personal and genetic risk of suicide but not in LCLs from suicide completers (p > 0.05). These findings were replicated in the Canadian sample and the analysis on the pooled dataset increased the power and the significance of our findings. In contrast with the gene expression findings the protein …