The Epigenetics of Suicide: Explaining the Biological Effects of Early Life Environmental Adversity
A number of recent studies have shown epigenetic alterations associated with suicidal behavior. These epigenetic mechanisms, which alter gene expression via alternative mechanisms to the coding DNA sequence, result from environmental effects acting on the genome. Studies in rodents indicate that variation in the early environment will trigger these epigenetic modifications and recent human data suggest the same may be true in humans.The expression of a number of genes, which are involved in normal brain functions and that have been shown to be under epigenetic control, seem to be dysregulated in suicide. The present review briefly describes the main epigenetic mechanisms involved in the regulation of gene expression and discusses recent findings of epigenetic alterations in suicidal behavior.
Available from: Claudia Schmauss
- "Early life stress can trigger changes in gene expression and behavior that persist into adulthood. It is widely recognized that early life stress is a risk factor for several psychiatric illnesses and one of the strongest predictors of negative mental health outcomes, including poor treatment responses and suicide123. About 1.5% of the population of the United States between the ages of 0 to 17 years have a documented history of early life stress, either in form of childhood neglect (~60%), physical abuse (~15%), or sexual abuse (~10%)4. "
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ABSTRACT: Using a rodent paradigm of early life stress, infant maternal separation (IMS), we examined whether IMS-triggered behavioral and epigenetic phenotypes of the stress-susceptible mouse strain Balb/c are propagated across generations. These phenotypes include impaired emotional behavior and deficits in executive cognitive functions in adulthood, and they are associated with increased acetylation of histone H4K12 protein (acH4K12) in the forebrain neocortex. These behavioral and epigenetic phenotypes are transmitted to the first progeny of IMS Balb/c mothers, but not fathers, and cross-fostering experiments revealed that this transmission is triggered by maternal behavior and modulated by the genetic background of the pups. In the continued absence of the original stressor, this transmission fades in later progenies. An adolescent treatment that lowers the levels of acH4K12 in IMS Balb/c mice augments their emotional abnormality but abolishes their cognitive deficits. Conversely, a treatment that further elevates the levels of acH4K12 improved the emotional phenotype but had no effects on the cognitive deficits. Moreover, treatments that prevent the emergence of either emotional or cognitive deficits in the mother also prevent the establishment of such deficits in her offspring, indicating that trans-generational effects of early life stress can be prevented.
Available from: Izabela Chojnicka
- "suggest a broad and possibly population specific role of the MTHFR variants on psychiatric phenotypes. Part of the predisposition to suicide is determined by genetic factors and suicide can be regarded as a distinct psychiatric phenotype (Arango et al., 2003; Brent and Mann, 2005; Labonte and Turecki, 2010). Although suicidal behavior has been associated with the number of loci (Baldessarini and Hennen, 2004), no prior study investigated whether it is linked with MTHFR C677T. "
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ABSTRACT: MTHFR C677T polymorphism (rs1801133) was associated with numerous psychiatric conditions but no prior study investigated whether it predisposes to completed suicide. We typed rs1801133 in 692 suicide victims and 3257 controls representative of a Polish adult population (the WOBASZ cohort). Although we had a power of 0.8 to detect (at alpha 0.05) an allelic OR=1.19, we did not find significant difference among suicides vs. controls in the prevalence of the MTHFR 677T allele (OR=1.02, p=0.759) or the TT genotype (OR=1.01, p=0.926). Since among controls we found an association between TT and depression defined by Beck Depression Inventory (BDI, OR=1.61, p=0.049) we also compared suicides with controls without signs of depression (BDI≤11) but found no association (OR=1.0, p=0.976). Analyses within suicides showed trends (not significant after Bonferroni correction) for correlations between the dose of the T allele and age at death among males and blood ethanol concentration among females, who committed suicide under the influence of alcohol. We conclude that MTHFR C677T polymorphism is not a risk factor for completed suicide. The sex-specific trends for correlations between rs1801133 and age at death, and blood ethanol concentration should be studied further.
Available from: Tiziana Angrisano
- "psychiatric disorders (Autry and Monteggia, 2009; Labonte and Turecki, 2010; Miller, 2010; Tsankova et al., 2007). Very interestingly, strong evidence support that epigenetic modifications in brain cells may be influenced by exposure to environmental factors including childhood abuse, stress, medicament, alcohol, drug use and diet (Sweatt, 2009; Szyf et al., 2008). "
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ABSTRACT: Alterations of DNA methylation and expression of suicide-related genes occurring in specific brain's areas have been associated to suicidal behavior. In the BDNF pathway, TrkB gene in frontal cortex and hippocampus, and BDNF gene in Wernicke area have been found hypermethylated and down-regulated in suicide subjects as compared to controls. In this work we investigated whether epigenetic modifications of TrkB gene occur in Wernicke area of 18 suicide subjects as compared to 18 controls.
MassArray analysis was performed to determine the methylation degree of TrkB promoter in post-mortem samples. TrkB full length and TrkB-T1 mRNA levels were assessed by quantitative RT-PCR. Geometric averaging of four internal control genes was calculated for normalization of results.
We found that TrkB and TrkB-T1 expression and promoter methylation in Wernicke area did not correlate with suicidal behavior whereas, in the same samples, the BDNF promoter IV was significantly hypermethylated in suicide with respect of controls.
Data from a single brain's area in this study's sample.
Our data show that no correlation exists between TrkB gene methylation and suicide in Wernicke area, confirming that expression and methylation state of suicide-related genes, even belonging to the same pathway, may be specific for brain area.
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