title: 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.
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Fiori
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bureau
authors.forename: Aurélie
authors.initials: A
authors.lastname: Labbe
authors.forename: Jordie
authors.initials: J
authors.lastname: Croteau
authors.forename: Simon
authors.initials: S
authors.lastname: Noël
authors.forename: Chantal
authors.initials: C
authors.lastname: Mérette
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
mesh_terms: D012437:Adenosylmethionine Decarboxylase / Q000235:genetics / Q000502:physiology; D001219:Aspartate Aminotransferases / Q000235:genetics; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000032:analysis; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D019964:Mood Disorders / Q000235:genetics* / Q000503:physiopathology; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics / Q000502:physiology; D011073:Polyamines / Q000378:metabolism*; D013095:Spermidine / Q000502:physiology; D013097:Spermine Synthase / Q000235:genetics / Q000502:physiology*; D013405:Suicide; D000097667:Polyamine Oxidase
chemical_list: D012437:Adenosylmethionine Decarboxylase; D001219:Aspartate Aminotransferases; D018076:DNA, Complementary; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D013095:Spermidine; D013097:Spermine Synthase; D000097667:Polyamine Oxidase