The Legacy of Inaction: How Prolonged Social Trauma Has Generational Epigenetic Impacts

Arguments over whether people are defined by their genes or their environments have been waged for years. This "nature versus nurture" discussion has long been debated, questioning how much experiences and genetics dictate how an individual looks, acts, and experiences life. An important piece of this discussion that has sparked new research is how some particular experiences can change the genetics of their descendants, or simply put, how nurture can change nature. This rising field is the study of social epigenetics, or the study of how social events can cause biological differences by changing the chemical markers on DNA, resulting in different gene expressions without changing the DNA structure itself [1;2]. This means that certain experiences, notably those that are socially traumatic like poverty, childhood abuse, and harassment, can not only affect the individual personally experiencing them but can work their way into the individual’s DNA. This is then passed down to their children, resulting in intergenerational trauma [2; 3]. In other words, people having these experiences not only face negative effects themselves but can also pass them on for generations to come, highlighting the importance of addressing and eliminating these stressful experiences as much as possible. 

The question now becomes how exactly a single experience can change the ways that genes are expressed. Before delving deeper, it is important to note that although there are biological processes that relate to social epigenetic changes, no research has established a causal relationship. With that disclaimer in mind, epigenetic changes are believed to be associated with DNA methylation, post-translational histone modifications, and non-coding RNAs [4]. DNA methylation is the process by which a methyl group (-CH3)  is attached at the fifth carbon (C-5) position of the cytosine ring on a DNA sequence. Researchers believe that this process is accomplished by DNA methyltransferases (DNMTs), enzymes that have the sole purpose of transferring methyl groups from the donor S-adenosyl-L-methionine (SAM) to the C-5 position. This is a necessary function in mammals to maintain the stability of the entire genome, but it has occurred with specific genes in relation to epigenetic effects [5]. Adding methyl groups shuts off the expression of the gene it is attached to, resulting in a change in the ways a person experiences and responds to events and feelings. 

One example of this is in the DNA of survivors of trauma with either a mother or both parents diagnosed with PTSD. These individuals had lower rates of methylation at the 1F promoter region of the glucocorticoid receptor gene (NR3C1), resulting in a greater sensitivity to glucocorticoids, a type of hormone that engages in many processes used to maintain homeostasis, or the normal order of the body [6]. This finding gave rise to current research about the role of cortisol, a glucocorticoid that is connected to stress [1]. Cortisol plays many key functions in the body, most notably, its regulation of the “fight or flight response.” It also plays a role in maintaining homeostasis in all the body’s systems [7]. This becomes evident in extreme cases since very high cortisol levels can lead to weight changes, mood swings, and high blood pressure [7]. High cortisol levels have effects on many body systems demonstrating its importance. Large fluctuations in cortisol levels over time can be linked to a higher sensitivity to cortisol, which can result in changes that ultimately yield negative health outcomes like metabolic and inflammatory diseases [8; 9]. The effects of methylation were also found in mice exposed to early life trauma, where researchers observed methylation on two different genes: the transcription enhancer region of the arginine vasopressin gene and the promoter region of the corticotropin-releasing factor gene. These mice were noted to experience anxiety and depression-like symptoms and difficulties with inhibitory avoidance which is the ability to avoid an environment in which a negative event occurred [10], demonstrating the psychological effects that epigenetic DNA methylation may have. These effects in mice suggest that there may be a similar effect in humans.

Another potential mechanism of social epigenetic changes is post-translational histone modifications. Histone proteins are wrapped in DNA and can be changed at their ends, also called terminal tails. These changes are called post-translational histone modifications. The most commonly studied of them is called acetylation, where an acetyl group (−COCH₃) is attached to the terminal tail of a histone by enzymes that specialize in moving acetyl groups, called acetyltransferases. The terminal tails have remnants of the amino acid lysine on them, which has a positive charge. When attached, a negatively charged acetyl group zeroes out the charge, allowing the histone protein to be more easily separated from the DNA [2]. This allows DNA and RNA to continue in their natural process of creating proteins. In some studies, rats who had experienced chronic stress showed differences in histone acetylation of their brain-derived neurotrophic factor (BDNF) promoters [2]. BDNF expression is partially responsible for the long-term development of neuron networks and the way those networks evolve in adulthood, meaning changes to them can have life-spanning effects [11]. 

The final suspected mechanism of epigenetic changes is long non-coding RNAs (lncRNA). These are defined as molecules that are usually longer than 2 kilobases (a measurement used for DNA and RNA equivalent to 100 base pairs each) that have “a coding potential of less than 100 amino acids” [12]. Non-coding RNAs outnumber coding RNAs, which are the type of RNA that guide the creation of proteins in the body, but there is little consensus on their function as a whole aside from them likely playing a role in translation and transcription. Studies of a few specific lncRNAs have found that they likely play a role in the silencing of certain genes [12]. This mechanism has been studied less than the former and thus does not have examples clearly demonstrating its effects.

These biological processes are quite complicated and can seem disconnected from the social stressors that are believed to be associated with them, but it is important to keep in mind that these studies have identified several statistically significant instances of each of these effects, meaning that these processes are not simply coincidental. Genetic changes like the aforementioned DNA methylation, post-translational histone modifications, and the actions of lncRNAs were all noted in instances where social stressors were present; the former two are connected to a family history of PTSD, a psychological illness occurring after experiences of trauma or chronic stress. These traumas can be precipitated by social stressors like childhood abuse or even experiences like poverty. Although these findings are not conclusive, they pave the path to understanding new ways in which stress impacts individuals.

As research emerges on the ways that social stressors biologically affect people not only in the present but across generations, the public health emergency around many of these psychosocial stressors only becomes more pressing. Personal characteristics that have often been attributed to either the way people are born or the experiences they have are increasingly being seen as some combination of both through this research. The stress caused by experiences such as childhood abuse, houselessness, and poverty have been connected to observable changes in the very DNA sequences that define people and their descendants. A change in the way one person experiences their feelings and responds to stress can carry across several generations, emphasizing the importance of addressing these issues early and comprehensively..  

References

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