McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
Int J Neuropsychopharmacol. 2011 Jun;14(5):595-605. doi: 10.1017/S1461145710001574. Epub 2011 Jan 6.
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.
近年来，基因表达、遗传关联和代谢研究表明，多胺系统与包括自杀在内的精神疾病有关。鉴于多胺代谢相关基因的广泛调控，以及它们与其他氨基酸代谢的相互联系，我们有兴趣进一步研究多胺相关基因在大脑中的表达，以更全面地了解该系统在自杀中的失调。为此，我们在 29 名心境障碍自杀完成者和 16 名对照者的样本中检查了 22 个大脑区域中与多胺代谢相关的基因的表达情况，并鉴定出 14 个基因表达存在差异。其中，精脒/精胺 N1-乙酰转移酶、精脒氧化酶和精脒合酶的表达改变以前在自杀完成者的大脑中观察到，而其余基因则代表新的发现。除了直接参与多胺代谢的基因，包括 S-腺苷甲硫氨酸脱羧酶、鸟氨酸脱羧酶抗酶 1 和 2 以及精氨酸酶 II 外，我们还鉴定出几个更远相关基因的表达改变，包括醛脱氢酶 3 家族成员 A2、脑肌酸激酶、线粒体肌酸激酶 1、甘氨酸酰胺转移酶、谷草转氨酶 1 和精氨酰-tRNA 合成酶样。这些基因中的许多在多个大脑区域显示出表达改变，强烈暗示失调的多胺代谢是自杀完成者大脑中的一种普遍现象。这项研究提供了一个更广泛的视角，了解多胺系统在自杀中的失调的性质和程度，并强调了该系统在自杀的神经生物学中的重要性。
