Evidence of Altered Polyamine Concentrations in Cerebral Cortex of Suicide Completers

Chen, Gary Gang; Fiori, Laura M.; Moquin, Luc; Gratton, Alain; Mamer, Orval; Mechawar, Naguib; Turecki, Gustavo

doi:10.1038/npp.2010.17

Cited by 53 publications

(38 citation statements)

References 68 publications

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“…This increased histone methylation was associated with decreased expression; however differences in DNA methylation were only seen in the frontal cortex (BA10) and not the cerebellum. Additionally, in line with the study on peripheral BDNF levels in antidepressant drug responders [57] previously described, a study using suicide brains found that antidepressants use had the same association of decrease in methylation at H3K27 and an increase in BDNF expression [71], again suggesting an influence of therapeutic drugs on histone modifications in humans similar to that seen in rodents [72].…”

Section: Chronological Agesupporting

confidence: 60%

Sensitive Periods in Epigenetics: Bringing us Closer to Complex Behavioral Phenotypes

Nagy

Turecki

2012

Epigenomics

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Genetic studies have attempted to elucidate causal mechanisms for the development of complex disease but genome-wide associations have been largely unsuccessful in establishing these links. As an alternative link between genes and disease, recent efforts have focused on mechanisms that alter the function of genes without altering the underlying DNA sequence. Known as epigenetic mechanisms, these include: DNA methylation, chromatin conformational changes through histone modifications, non-coding RNAs, and most recently, 5-hydroxymethylcytosine. Though DNA methylation is involved in normal development, aging and gene regulation, altered methylation patterns have been associated with disease. It is generally believed that early life constitutes a period during which there is increased sensitivity to the regulatory effects of epigenetic mechanisms. The purpose of this review is to outline the contribution of epigenetic mechanisms to genomic function, particularly in the development of complex behavioral phenotypes, focusing on the sensitive periods.

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Section: Chronological Agesupporting

confidence: 60%

Sensitive Periods in Epigenetics: Bringing us Closer to Complex Behavioral Phenotypes

Nagy

Turecki

2012

Epigenomics

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“…This technique was specifically developed for the extraction and quantification of spermine, spermidine, putrescine, and agmatine from postmortem brain [57,58,59]. Using GC-MS, it was shown that putrescine and spermidine levels were significantly elevated in the brains of depressed suicide completers [60], thus lending further support to the idea that decreases in SAT1 expression in depressed suicide completers are likely the result of a feedback regulation.…”

Section: -Protein Levels Of Polyaminesmentioning

confidence: 89%

Suicide and the Polyamine System

Gross¹,

Turecki

2013

CNSNDDT

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Suicide is a significant worldwide public health problem. Understanding the neurobiology is important as it can help us to better elucidate underlying etiological factors and provide opportunities for intervention. In recent years, many lines of research have suggested that the polyamine system may be dysregulated in suicidal behaviors. Initial research in animals provided evidence of a dysfunctional polyamine stress response system, while later work using post-mortem human brain tissue has suggested that molecular mechanisms may be at play in the suicide brain. In this review, we will describe the research that suggests the presence of alterations in the polyamine system in mental disorders and behavioral phenotypes, with particular attention to work on suicide. In addition, we will also describe potential avenues for future work. KeywordsEpigenetics; Major Depressive Disorder; Neurobiology; Polyamines; Polyamine Stress Response; Spermidine/Spermine-N 1 -Acetyltransferase; Suicide -IntroductionSuicide, most often associated with major depressive disorder (MDD) [1], is an important cause of premature death around the world [2]. According to the World Health Organization (www.who.int, 2012), approximately one million people die by suicide annually, and the rate of suicide attempts is 20 times greater than that of suicide completion (www.who.int, 2012). As such, suicidal behaviors (SB) are an important source of public health concern. The etiology of suicide is complex [3], and commonly understood as resulting from the interaction of predisposing (distal) and precipitant (proximal) factors [4]. Biological alterations resulting from a combination of genetic and environmental risk factors underlie predisposition to suicide, but the exact molecular mechanisms at play remain largely unclear. As such, it is important that we gain a better understanding of the molecular processes associated with suicide in order to identify new avenues for prevention and intervention.Over the past several decades, molecular studies of suicide and MDD have focused on the monoamine system. Beginning in the late 1960s, research into the neurobiology of suicide

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“…The PSR, like the HPA axis, is implicated in physiological responses to physical, emotional and hormonal stressors, including glucocorticoids (BOX 4). The mRNA and protein levels of several components of the polyamine system are altered in cortical and subcortical brain regions of suicide completers [125][126][127][128] , as well as in peripheral samples from suicide attempters 129,130 and psychiatric patients 131 .…”

Section: Trait Markersmentioning

confidence: 99%

The molecular bases of the suicidal brain

2014

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Suicide ranks among the leading causes of death around the world and takes a heavy emotional and public health toll on most societies. Both distal and proximal factors contribute to suicidal behaviour. Distal factors - such as familial and genetic predisposition, as well as early-life adversity - increase the lifetime risk of suicide. They alter responses to stress and other processes through epigenetic modification of genes and associated changes in gene expression, and through the regulation of emotional and behavioural traits. Proximal factors are associated with the precipitation of a suicidal event and include alterations in key neurotransmitter systems, inflammatory changes and glial dysfunction in the brain. This Review explores the key molecular changes that are associated with suicidality and discusses some promising avenues for future research.

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Evidence of Altered Polyamine Concentrations in Cerebral Cortex of Suicide Completers

Cited by 53 publications

References 68 publications

Sensitive Periods in Epigenetics: Bringing us Closer to Complex Behavioral Phenotypes

Sensitive Periods in Epigenetics: Bringing us Closer to Complex Behavioral Phenotypes

Suicide and the Polyamine System

The molecular bases of the suicidal brain

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