Global gene expression profiling of the polyamine system in suicide completers.
ABSTRACT In recent years, gene expression, genetic association, and metabolic studies have implicated the polyamine system in psychiatric conditions, including suicide. Given the extensive regulation of genes involved in polyamine metabolism, as well as their interconnections with the metabolism of other amino acids, we were interested in further investigating the expression of polyamine-related genes across the brain in order to obtain a more comprehensive view of the dysregulation of this system in suicide. To this end, we examined the expression of genes related to polyamine metabolism across 22 brain regions in a sample of 29 mood-disordered suicide completers and 16 controls, and identified 14 genes displaying differential expression. Among these, altered expression of spermidine/spermine N1-acetyltransferase, spermine oxidase, and spermine synthase, has previously been observed in brains of suicide completers, while the remainder of the genes represent novel findings. In addition to genes with direct involvement in polyamine metabolism, including S-adenosylmethionine decarboxylase, ornithine decarboxylase antizymes 1 and 2, and arginase II, we identified altered expression of several more distally related genes, including aldehyde dehydrogenase 3 family, member A2, brain creatine kinase, mitochondrial creatine kinase 1, glycine amidinotransferase, glutamic-oxaloacetic transaminase 1, and arginyl-tRNA synthetase-like. Many of these genes displayed altered expression across several brain regions, strongly implying that dysregulated polyamine metabolism is a widespread phenomenon in the brains of suicide completers. This study provides a broader view of the nature and extent of the dysregulation of the polyamine system in suicide, and highlights the importance of this system in the neurobiology of suicide.
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ABSTRACT: A recent publication focused on biomarkers of future suicidal behaviors identifies several genes expressed in high-risk states among four samples. We discuss the implications of this study as well as the current state of research regarding biomarkers of suicidal behavior.Current Psychiatry Reports 12/2013; 15(12):424. · 3.05 Impact Factor
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ABSTRACT: Suicide and suicidal behaviors are complex, heterogeneous phenomena that are thought to result from the interactions among distal factors increasing predisposition and proximal factors acting as precipitants. Epigenetic factors are likely to act both distally and proximally. Aspirational Goal 1 aims to find clear targets for suicide and suicidal behavior intervention through greater understanding of the interplay among the biological, psychological, and social risk and protective factors associated with suicide. This paper discusses Aspirational Goal 1, focusing on the research pathway related to epigenetics, suicide, and suicidal behaviors. Current knowledge on epigenetic factors associated with suicide and suicidal behaviors is reviewed and avenues for future research are discussed. Epigenetic factors are a promising area of further investigation in the understanding of suicide and suicidal behaviors and may hold clues to identifying targets or avenues for intervention.American Journal of Preventive Medicine 09/2014; 47(3):S144–S151. · 4.28 Impact Factor
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ABSTRACT: Changes in the blood expression levels of SAT1, PTEN, MAP3K3 and MARCKS genes have been reported as biomarkers of high versus low suicidality state (Le-Niculescu et al.). Here, we investigate these expression biomarkers in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study, of patients with major depressive disorder on a 12-week antidepressant treatment. Blood gene expression levels were available at baseline and week 8 for patients who experienced suicidal ideation during the study (n=20) versus those who did not (n=37). The analysis is well powered to detect the effect sizes reported in the original paper. Within either group, there was no significant change in the expression of these four genes over the course of the study, despite increasing suicidal ideation or initiation of antidepressant treatment. Comparison of the groups showed that the gene expression did not differ between patients with or without treatment-related suicidality. This independent study does not support the validity of the proposed biomarkers.Translational psychiatry. 10/2014; 4:e474.