Ssat Gene Expression Changes in Schizophrenia and Its Implication with Suicide

Sequeira, A et al
International Congress on Schizophrenia Research. 2009:150.


Schizophrenia patients have high rates of suicide. However, only a subset of schizophrenia patients ever attempt or commit suicide. In the past half decade, there have been a number of studies utilizing microarray technology to conduct genome wide screenings of gene expression changes in postmortem brain tissue leading to potential candidate genes for suicide that have not been investigated in the schizophrenia context. The purpose of this study was to investigate if spermidine/spermine N1-acetyltransferase (SSAT) gene expression, a previously confirmed gene for suicide1, plays a role in either schizophrenia or suicide in schizophrenia. We used Affymetrix HG-U133 Plus2, Illumina HumanRef-8 Expression BeadChip, as well as RT-PCR expression data to compare SSAT levels in schizophrenic patients who committed suicide (S-Schz (N = 4)), non-suicide schizophrenic patients (NS-Schz (N = 10)) and controls (N = 44) in the dorsolateral prefrontal cortex (DLPFC). Brain tissue was obtained through the University of California, Irvine Brain Bank following approval by the Institutional Review Board. Analysis was performed correcting in an ANOVA model for demographic variables (age, gender) and quality control parameters (pH and RNA degradation) using PARTEK. SSAT was differentially expressed in both platforms when comparing all schizophrenia subjects to controls and when comparing those schizophrenia subjects who committed suicide (S-Schz) to controls. However, SSAT expression was not significantly different between non-suicides schizophrenia patients (NSSchz) and controls. We confirmed the schizophrenia and suicide specific results using RT-PCR SYBRGreen expression levels data. In summary, SSAT gene expression is altered in the DLPFC of schizophrenic patients when compared to controls and more specifically in schizophrenic patients who committed suicide. This confirms the previously reported implication of SSAT in suicide and points out to a possible biomarker or therapeutic target for suicide across diagnostics. SSAT is the rate-limiting enzyme in the catabolism of polyamines and this study extends the implication of the polyamine system in suicide in schizophrenic patients.
1. Sequeira A, Gwadry FG, Ffrench-Mullen JM, Canetti L, Gingras Y, Casero RA Jr, Rouleau G, Benkelfat C, Turecki G. Implication of SSAT by gene expression and genetic variation in suicide and major depression. Arch Gen Psychiatry. 2006;63(1):35-48.