**7. Post-traumatic stress and anxiety**

The intense stress caused by imposed to stressful experiences, battle for example, genocide, starvation, elevates the liability of psychiatric wellbeing problems, including PTSD, schizophrenia, depression, even killing oneself [36, 37]. Similarly, US fighting veterans with an analysis of moderate PTSD showed hypomethylation on the regulatory portion of the NR3C1 promoter 1F and decreased HPA axis actions [109]. As a result, in the meantime NR3C1 is a very typical target for epigenetic modifications as a response upon these distinctive stress forms, in addition to qualitative discrepancies in the mechanisms as well as the context of traumatic events themselves, the particular variations within the patterns of NR3C1 methylation could represent disparities in the timings as well as times of coverage for trauma.

Traumatic stress and PTSD-associated variance in DNA methylation at the SKA2 locus have been reported in recently made studies on epigenetic alterations among war vets suffering extreme PTSD [110, 111]. SKA2 encodes a protein that is rather to

### *Epigenetic DOI: http://dx.doi.org/10.5772/intechopen.99964*

serve as a chaperone or possibly a GR activity regulator, allowing negative feedback to the HPA axis mediated by cortisol dependent GR. SKA2 was recognized as a hypermethylated, under expressed locus of suicide completers in post-mortem cortical tissue, and variance in SKA methylation was also correlated with suicidal activities in PTSD individuals [112, 113]. Although the discovery of altered DNA methylation taken from those who tried to commit suicide and who suffers PTSD at this locus in tissue indicates possible functions for SKA2 in the control of traumatic stress response, it is presently uncertain if these modifications are directly linked to the multiple psychopathological behaviors under investigation.

In intergenerational epigenetic responses to stress, research on the effects of PTSD suffered by those who survived Holocaust through their offspring includes modified HPA axis actions, and even more especially dysregulation of the GR along with its auxiliary components. In a similar study, methylation with a CpG dinucleotide inside a GR binding website inserted within an intron of this gene encoding the GR regulator FKBP5 was shown to be increased within the blood cells of Holocaust survivors, as well as lower in their offspring, relative to the quantity of this gene encoding the GR regulator FKBP5 [114]. These findings show that intergenerational transfer of trauma-related DNA methylation modifications has taken place between Holocaust survivors and descendants of theirs in at least a variety of cases. In response to a new, moderately demanding exposure, diminished behavioral regulation was recognized as diminished latency to type in unknown places, indicative of probably elevated resistance or impulsivity. Additionally, DNA methylation switches at candidate gene loci transmitted via the germline along with mediated, transmitted behavioral anomalies from the MSUS. The applicant genes include Nr3c1, which demonstrated decreased methylation of the promoter and increased transcription of this progeny of MSUS treated mice in the hippocampus. In addition, traumatized men's sperm contained microinjection and trauma-induced miRNAs of distilled RNA derived from their traumatized adult men's sperm recapitulated MSUS-induced behavioral abnormalities, suggesting functions within the intergenerational transmission of trauma-induced phenotypes for these very short noncoding RNAs. Interestingly, the intergenerational transfer of MSUS mediated altered behavioral reactions to moderately challenging stimuli, increased Nr3c1 methylation, and decreased transcription of this specific gene within the hippocampus was improved by environmental enrichment. In a related study, corticosterone administration to adult male mice caused behavioral phenotypes that indicated hyper nervousness within their male F1 progeny, as well as reduced anxiety levels, but elevated depressed characteristics within their F2 progeny. In addition, both the F1 and F2 phenotypes have been identified with the expression within the paternal sperm of some corticosterone mediated miRNAs. Taken together, these animal experiments suggest that ameliorative and negative interactions modulate behavior, the effects of which could be delivered among one descendant to the others, possibly by epigenetic modulation of neuroendocrine reaction systems involving miRNAs [115].
