Involvement of SSAT in Depression in Post-Mortem Brains

Sequeira A, Mamdani F, Limon-Ruiz A, Rollins B, Morgan L, Bunney W, Vawter M
Annual Meeting of the American College of Neuropsychopharmacology. 2015.


Background: Depression and suicidal behaviors are often observed in the same patients. However, only a subset of mood disorder patients ever attempt or complete suicide. Spermidine/Spermine N1-Acetyltransferase 1 is the rate limiting enzyme in the catabolism of polyamines and has been shown to be dysregulated in depressed suicides and in bipolar subjects with suicidal behaviors. The purpose of this study was to investigate brain gene expression changes associated with suicide in mood disorder patients in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC) and the nucleus accumbens (NACC).

Methods: Gene expression levels were of major SSAT1 isoforms were investigated by QPCR in a sample of 46 MDDs (18 non-suicides/26 suicides) and 20 Controls. Affymetrix HG-U133 Plus2.0 microarray chips data was available for a subset on subjects and was used for correlation analyses with other polyamine genes. Statistical analysis was performed using Partek Genomics Suite and an ANCOVA model was used to identify the differentially expressed genes between non-suicides and suicide controlling for age, gender, pH, and RNA degradation. Confirmation of results was performed by Western Blot using a Protein Simple imaging system and a commercially available anti-SSAT1 antibody (Novus).

Results: No correlation between gene expression levels and age, gender, pH or RNA degradation measures was observed. We confirmed the previously reported decrease in SSAT expression in depressed suicides and major depression subjects. We also observed a similar decrease in expression of another SSAT variant (isSSAT1) in major depressed subjects across brain regions. However, suicide overall did not play a major role as a factor in SSAT1 expression levels. Globally, expression levels were highly correlated between the most common SSAT1 isoforms across brain regions.

Conclusions: Major depressive disorder is a complex, multifactorial disorder, characterized by a significantly higher risk of committing suicide than the general population. Few post-mortem gene expression studies have been able to compare suicide versus non-suicide gene expression levels in post-mortem brains, and none have actually combined gene expression with protein expression in the same cohort. The identification of depression versus suicide risk factors could also lead to potential drug targets and a fundamental understanding of the molecular basis of these complex behaviors. Our findings support the involvement of the polyamine system and particularly of SSAT1 in major depression. The role of SSAT1 in suicide specifically is less clear as no suicide specific effect was observed.