Abstract

Adverse Childhood Experience (ACE), impactful and traumatic situations occurring during an individual’s childhood, is extremely prevalent worldwide and results in depression, anxiety, post traumatic stress disorder (PTSD) and many other mental disorders. A notable example from the past is the Canadian genocide of Indigenous people; most Indigenous children experienced ACE in multiple forms due to the unethical assimilation methods put in place by the Canadian government. Today, one in six adults globally have experienced at least four types of adverse childhood experience, five of ten leading causes of death are associated with ACE, and prevention of these experiences could reduce the rate of adults with depression by 44%. With the rise of epigenetics, the struggles of these people should be recognised and prevented beyond the first generation. Intrauterine exposures and intergenerational epigenetic inheritance, as well as the theory of transgenerational epigenetic inheritance (TEI), have sparked interest in the generational impacts a traumatic environment can have without modifications of the genetic code itself.  This paper aims to examine the link between epigenetics and ACE, preventing future trauma inflicted on subsequent generations. We propose the Family-Directed Model (FDM) as a step to counteract and prevent adverse childhood experiences.

Overview (Introduction)

Adverse Childhood Experiences (ACEs) are traumatic events that happen in one’s childhood from the ages 0-17, according to the Centers for Disease Control and Prevention (CDC). Trauma events can include: neglect, violence, abuse or instability at home, such as parental substance abuse, mental illnesses, parental separation or death of a close relative (CDC, 2023a; CDC, 2023b). ACEs can have negative lasting effects that continue into adulthood, such as increased risk in mental health disorders like anxiety or depression. These experiences can disrupt a child’s personal development and impact their social and psychological behaviours.

Developing research indicates that the impacts of ACE can become further embedded through the process of epigenetics. Epigenetics is the study of changes to the genome that do not alter the underlying DNA sequence but instead affect how genes are expressed. Environmental factors modulating these alterations include diet, severe trauma and stress endured during childhood leaving lasting imprints on the genes (Dillinger, n.d.). These marks can act as switches, turning the gene on or off, therefore modulating gene expression. This can lead to a change in immune function, brain development and how a person responds to stress. Importantly, new scientific studies introduced how these “stress-related” marks are not confined solely to the individual themselves but can be passed down through generations (Bohacek, J & Mansuy, I.M, 2015).

Transgenerational Epigenetic Inheritance (TEI) refers to how these epigenetic marks from parents to offspring can be transmitted without any exposure to the original environmental stressor. The fundamental correlation between adverse childhood experiences and TEI lies in understanding the severity of trauma endured during childhood and how it can leave biological imprints. Animal models, such as rodents, have been used as definitive evidence to support TEI, as researchers were able to deduce how social influences and maternal separation altered stress responses, metabolism and changes in brain development. In these animal-related experiments, changes in histone modifications, DNA methylation patterns and non-coding DNA regions indicated that environmental stressors can induce stable epigenetic alterations across generations (Collender et al., 2023). Epigenetic changes observed in the F0 generation were found to reappear in subsequent generations (F1, F2 and even F3) despite these later generations being raised in stress-free laboratory environments; they still exhibited epigenetic modifications. This provides strong evidence that the effects of trauma are not solely inherited genetically but can also be transmitted epigenetically across generations. ACEs trigger the activation of the body’s stress response system, known as the Hypothalamic-Pituitary-Adrenal (HPA) axis, leading to elevated cortisol levels and impacting cellular machinery, which is important for epigenetic modifications. Specifically, long-term exposure to high cortisol levels can add or remove chemical “tags” and altering the process of DNA methylation can influence how genes are expressed, leading to disparities not only biologically but also psychologically. 

Understanding this correlation will help the conceptualisation of both physical and mental health conditions and will facilitate our understanding of the biological legacies of trauma that can be passed down through generations. ACEs can alter the way the body and brain function. Brain development during a critical stage of growth is impaired, like shrinkage in the prefrontal cortex, and hyperactivity in the amygdala, changing the individual’s response to stress. The physical health impacts include hormone imbalance and impaired immune function, resulting in a greater risk for developing diseases. This eventually could pass down epigenetic marks to the individual’s children, causing future generations to also have a greater risk (CDC, 2020). Therefore, preventing ACE is crucial not just for the wellbeing of one individual but for the generations to come. Creating a new lens for prevention strategies, as well as public health policies, is imperative, as the effects of childhood trauma can be passed down.

Beyond animal models for understanding the correlation of TEI and ACEs, there are several human studies (Jawaid, Roszkowski & Mansuy, 2018). Research on the effects of the Holocaust on survivors and their descendants showed unique alterations on the stress gene known as FKBP5 (Bierer et al., 2014). The children of the survivors, while they were indirectly exposed to their parents’ trauma through a shared environment, did not directly experience the Holocaust themselves. This finding strongly evidences how one generation can transmit specific epigenetic modifications that influence stress-sensitivity, as well as the biological impact of ACEs (Bierer et al., 2014). Similarly, Pang et al.’s study discusses how paternal stress can severely impact a child’s mental health and can potentially impact future generations (Pang et al., 2017).

A comprehensive understanding of the multigenerational effects of childhood trauma has the potential to transform public health policies and the lives of millions of people who suffer maltreatment in their lifetime. The authors of this paper suggest investments in early childhood support programmes, trauma-related support and comprehensive public policies designed to address adversity within communities. Emphasising these policies within different systems, whether it be in healthcare, schools or social services, in nations globally would considerably impact the lives of many. This would release the burden of stress-related epigenetic modifications across many generations to come and reducing the risk of disease susceptibility. It is important we advocate not only for the importance of the individual themselves but also for the generations to come. TEI and ACE are intrinsically connected, not just for individual biology but for public health populations across the globe (Yehuda, R & Lerner, A, 2018).

Canada’s Genocide & the Adverse Childhood Experience of Indigenous People 

There are many studies that examine the extent of intergenerational and transgenerational epigenetic inheritance. Examples include research on the inter- and transgenerational impact of the trauma suffered by the victims of Germany’s genocide during the Nazi regime, a Swedish study observing the transgenerational effects of the Dutch famine, and research on pregnant women and their offsprings after the physical and psychological trauma of 9/11.

For this paper, the topic of Canada’s genocide of Indigenous people was chosen to shed light on an often overlooked attempt to erase Indigenous culture, assimilate them among the Canadians and isolate them from their community (Matheson et al., 2022). 

One of the methods used by the Canadian government was the Indian Residential School (IRS) system. Beginning 1879 until 1997, all Indigenous children were required to attend church-run residential schools with extreme policies suppressing their culture and forcing assimilation. These policies forbade Indigenous children from speaking their own languages, engaging in their spiritual traditions or maintaining their cultural practices. It was later revealed that punishment, bullying, control, neglect, starvation and physical, emotional and sexual abuse were common in these schools.

In 2008, the Canadian government issued a formal apology to the Indigenous community and created the Truth and Reconciliation Commission (TRC) to investigate human rights injustice and promote reconciliation within a society. The commission was required to document the history of the IRS system, gather the testimonies of survivors and develop solutions for reintegrating the Indigenous community into Canada. Ultimately, it was through this programme that people began to recognise the ACE experienced by the Indigenous children and its overall negative effect on the Indigenous population.

Main Variables of Interest & Insights from Prior Studies

In prior studies, the relationship between mental illnesses and epigenetics has been observed and analysed in an animal model regarding FKBP5, a gene for the glucocorticoid receptor regulator FK506 binding protein 51 (Sabbagh et al., 2014). Similarly, epigenetic changes of NR3C1, neuron-specific exon 17 glucocorticoid receptors (McGowan et al., 2009) have also been studied, focusing more on the effects of ACE. These are both responsible for regulating the body’s stress response and are linked to increased risk of depression, anxiety and PTSD (Sabbagh et al., 2014; McGowan et al., 2009). 

Sabbagh et al.’s research focused on the FK506 binding protein 5 (FKBP5) gene through an animal model based on wild-type mice. Many tests were performed on the mice, but the most relevant towards epigenetics was DNA methylation analyses conducted on mice aged 1, 3.5, 4, 5, 6 and 12 months old. The results supported the idea that FKBP5 methylation has a negative relationship with the mice’s age, suggesting a positive relationship between age and FKBP51 levels. Elevated FKBP51 levels contribute to risk of depressive behaviours and other psychological challenges through impaired glucocorticoid signalling. The results show that the weakened stress-resiliency and glucocorticoid signalling occurs by 10 months old and increases throughout their lives. Therefore, Sabbagh and his team conclude, using an animal model, that the epigenetic modification of FKBP51 throughout the ageing process can impair psychological stress-resiliency. 

With regards to the NR3C1 gene, a 2009 study demonstrated that the HPA stress response is altered when exposed to ACE and increases the risk of suicide (McGowan et al., 2009). By examining the epigenetic differences in the NR3C1 promoter of suicide victims with ACE and suicide victims without, it was discovered that those with ACE had decreased levels of glucocorticoid receptor mRNA and mRNA transcripts bearing the glucocorticoid receptor 1F splice variant, while there was an increase in cytosine methylation of an NR3C1 promoter. Additionally, decreased NGFI-A transcription factor binding and NGFI-A-inducible gene transcription were shown from patch-methylated NR3C1 promoter constructs that mimicked the methylation state in samples from suicide victims with a history of ACE. These results from McGowan et al.’s research support the idea that parental care and ACE has an effect on the epigenetic regulation of hippocampal glucocorticoid receptor expression.

While intergenerational and transgenerational epigenetic inheritance are difficult to prove in humans, these phenomena have been observed in smaller mammals. Franklin et al. state that epigenetic marks are transmitted from males and affect offspring in a sex-dependent manner. Early life stress, especially neglectful parents, maternal deprivation and poor maternal care, alters DNA methylation in the germline of the affected males, resulting in either increased or decreased methylation depending on the locus (Franklin et al., 2010). These modifications persist in the individual with first contact and also subsequent generations. This animal model indicates the possibility that certain people’s predisposition to depression, anxiety, addiction, borderline personality disorder, attention deficit disorder, poor mood regulation, etc. can be effects of individuals exposed to early stress that was later transmitted through future generations (Franklin et al., 2010). Therefore, it supports intergenerational and transgenerational epigenetic inheritance in animals and can suggest the possibility of similar outcomes in humans.

Challenges to the Study on Canada’s Indigenous Genocide

Unfortunately, no formal research has been conducted on the relationship between Canada’s Indigenous genocide, Indigenous children who attended IRS, and the intergenerational and transgenerational epigenetic inheritance. This is due to the vague and inconsistent terms such as historical trauma, the lack of culturally-responsive tools, ethical issues regarding colonial power dynamics and cultural safety, execution of Indigenous perspectives, risk of politicising research and being unable to generalise the results beyond the specific sample (Gone & Kirmayer, 2020). The power dynamic between the primary inhabitants of the land and the minority groups have not been fully resolved and more work should be put into the reinforcement of their relationship. Indigenous people have already faced extreme challenges and betrayal by the Canadian government, so researchers would need to take extra sensitive care with the Indigenous community’s trust with their trauma.

Furthermore, researching TEI in itself poses many difficulties. Studies involving multiple generations in humans is not only time consuming but also costly, limiting the available data (Fitz-James & Cavalli, 2022). Moreover, while it is possible to create a controlled and observable environment for experimental animals, such cases are unethical and impossible to recreate for humans (Fitz-James & Cavalli, 2022). Additionally, due to the adaptable nature of epigenetic marks, it is challenging to determine the clear cause as inheritance rather than an environmental change (Fitz-James & Cavalli, 2022). This, in turn, is difficult to prove and observe within humans because of the limitations of experimental human models. 

Overall, there has yet to be a conclusive and formal study on the effects of Canada’s genocide on the Indigenous community. While there are studies that review pre-existing research on intergenerational and transgenerational epigenetic inheritance, and apply the knowledge into the context of Indigenous genocide, there is no specific research geared for ACE of Indigenous children and its epigenetic effects. Hopefully, this would serve as an inspiration and motivator for scientists to pursue research regarding this aspect and community.

Proposal: Model to Combat ACE

ACE and transgenerational epigenetics can often be ignored as a contributor for long-term harm for individuals, families, communities and generations. Symptoms that present into adulthood include trust issues, poor emotional regulation, poor stress management and difficulties engaging with wider society. We must emphasise prevention by providing early support to the offspring of victims and preventing the trauma before it happens. 

In order to combat and lower the chances of child abuse and other triggers of early trauma, we propose the Family-Directed Model (FDM) as a worldwide strategy that aims to prevent trauma from occurring. By including counselling and emotional support for parents, guardians and caretakers during a child’s routine medical visits, this model emphasises early intervention. As previously mentioned, ACE is a collection of various impactful and traumatic events within a child’s key development stage. Among these is abuse, but a lesser recognised event is neglect. After giving birth, postpartum depression is a common occurrence which, without the correct support system, can make it difficult to meet the baby’s needs. Through FDM’s regular counselling and emotional support for parents and guardians, neglect is less likely to occur. 

Diving deeper into the methods of this model, the parent or guardian would have access to an approved mental health professional each time the child visits the doctor for a checkup. The goal of these sessions is to support and educate the guardian, not to diagnose mental illnesses or search for problems. The parent has the opportunity to ask questions, discuss parenting challenges bluntly, and learn ways to handle discipline and healthy emotional communication. They are able to receive guidance from a therapist or counsellor on common situations such as managing stress or handling tantrums. The counsellor would also benefit from additional training on how to identify and gently address early indicators of family stress or potentially hazardous situations for a child. This model aims to provide parents, guardians and caretakers with support and assistance before anything negative occurs. By teaching healthy, productive ways to connect with and care for children, the FDM helps break the cycle of generational trauma.

The education that takes place outside of appointments is another strong piece of the process of the FDM. Those involved in the programme would have access to free printed guides, online videos and phone group chats available in various languages. These resources would provide information on topics such as how childrens’ brains develop, how parents can control their emotions and how to respectfully set boundaries. The model helps eliminate the shame that many parents experience by creating an opportunity for people to freely discuss experiences, ask questions and access support. Families experience less confusion as a result, and children are more likely to grow up in happy, caring environments.

The survivors of the IRS system provide one of the most compelling examples for understanding the need for early intervention today. As adults, survivors frequently dealt with identity crises, anxiety, depression and trust issues, and many carried these difficulties into their parenting. The Family-Directed Model aims to meet families where they are and provide the assistance they require before an obstacle develops.

Conclusion

In conclusion, ACE can be described as early life stressors and may include factors such as abuse, neglect and general household dysfunction. These have been historically associated with adverse health outcomes that manifest later in life. Additionally, due to recent scientific advances, we have gained a deeper understanding of the biological mechanisms through which ACEs may influence the lives of victims. Through the development of the epigenetic field, we have gained a greater understanding of how trauma may cause long lasting effects in gene expression of future generations during critical developmental periods. The phenomenon that results in these changes being passed on to subsequent generations has come to be known as TEI. The relevance these studies and observations provide is increasingly clear when applied to populations that have experienced historical and systemic trauma. The context of the Canadian nation’s residential school system, established to forcibly assimilate Indigenous children, serves as a glaring example. From the late 19th century until the late 20th century, Indigenous children were forcibly removed from their families and placed in institutions where they were forbidden from speaking their native tongues or practising their cultures, in addition to being cut off from their communities. The partaking institutions were also hotspots of physical, sexual and emotional abuse. Despite these obvious traumatic events endured by many young children, the long-term biological consequences of these policies have yet to be fully explored through the lens of epigenetics. While definitive epigenetic studies specific to the Canadian Indigenous context are still lacking, existing research on other similar populations provides a strong base for further investigation. Hopefully, this will further motivate scientists to study the lesser recognised situations. 

Although research is an important aspect, the most productive way to combat and prevent generational ACE related epigenetic problem is to develop a guiding model. We propose the FDM, a comprehensive, trauma-informed framework to beintegrated across healthcare, education and social services, aimed at supporting parents, guardians and caregivers, enhancing early learning environments, and promoting emotional resilience in children to buffer the effects of hardships or traumatic events. Moreover, widespread education about ACEs and epigenetics could foster a deeper societal understanding of trauma’s enduring effects and the need for preventative action. 

The growing body of evidence linking ACEs to TEI reveals that trauma’s impact is far-reaching in biological, psychological and social aspects. From experimental models to real-world case studies, the data points to a critical insight. Trauma can be passed down not only through stories and behaviours but through gene expression itself. The consequences of this reality are particularly salient in communities affected by systemic oppression and historical trauma, such as Indigenous peoples in Canada. To break this cycle, there must be sustained investment in prevention, healing and research that revolves around affected communities. Through these actions, society can shift from feeding the biological legacy of trauma to fostering resilience, health and justice across generations to come.

Bierer, L.M., Bader, H.N., Daskalakis, N.P., Lehrner, A., Provençal, N., Wiechmann, T., Klengel, T., Makotkine, I., Binder, E.B. & Yehuda, R. (2020). Intergenerational effects of maternal Holocaust exposure on FKBP5 Methylation. American Journal of Psychiatry, 177(8), p.appi.ajp.2019.1. doi:https://doi.org/10.1176/appi.ajp.2019.19060618.

Bohacek, J. & Mansuy, I.M. (2015). Molecular insights into transgenerational non-genetic inheritance of acquired behaviours. Nature Reviews Genetics, 16(11), pp.641–652. doi:https://doi.org/10.1038/nrg3964.

Bombay, A., Matheson, K. & Anisman, H. (2013). The Intergenerational Effects of Indian Residential Schools: Implications for the Concept of Historical Trauma. Transcultural Psychiatry, [online] 51(3), pp.320–338. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC4232330/ [Accessed 18 Jul. 2025].

CDC (2020). Adverse childhood experiences (ACES). [online] www.cdc.gov. Available at: https://www.cdc.gov/violenceprevention/aces/index.html.

CDC (2024). About adverse childhood experiences. [online] U.S. Centers for Disease Control and Prevention. Available at: https://www.cdc.gov/aces/about/index.html.

Centers for Disease Control and Prevention (2021). About the CDC-Kaiser ACE Study. [online] www.cdc.gov. Available at: https://www.cdc.gov/violenceprevention/aces/about.html.

Centers for Disease Control and Prevention (2021). Adverse childhood experiences (ACEs). [online] Centers for Disease Control and Prevention. Available at: https://www.cdc.gov/vitalsigns/aces/index.html [Accessed 26 Jul. 2025].

Collender, P.A., Bozack, A.K., Veazie, S., Nwanaji‐Enwerem, J.C., van, Kogut, K., Riddell, C., Eskenazi, B., Holland, N., Deardorff, J. & Andrés Cárdenas (2023). Maternal adverse childhood experiences (ACEs) and DNA methylation of newborns in cord blood. Clinical Epigenetics, 15(1). doi:https://doi.org/10.1186/s13148-023-01581-y.

Center, M.H. (2023). 9 Symptoms of Childhood Trauma in Adulthood. [online] Mental Health Center. Available at: https://www.mentalhealthctr.com/9-symptoms-of-childhood-trauma-in-adulthood/.

Chief, K., Copeland, J.L., Metz, G.A.S. & Currie, C.L. (2019). The biological impacts of Indigenous residential school attendance on the next generation. SSM – Population Health, [online] 7(100343), p.100343. Available at: https://www.sciencedirect.com/science/article/pii/S2352827318302933#ab0010 [Accessed 18 Jul. 2025].

Chief, K. (2014). The Biological Impacts of Residential Schooling on the Development of Intergenerational Trauma Among Indigenous People. [online] Available at: https://opus.uleth.ca/server/api/core/bitstreams/8c156d47-9259-485e-ae24-320f27da3373/content [Accessed 18 Jul. 2025].

Dillinger , S. (n.d.). Complete Guide to Understanding Epigenetics. [online] www.activemotif.com. Available at: https://www.activemotif.com/epigenetics-101.

Fitz-James, M.H. & Cavalli, G. (2022). Molecular mechanisms of transgenerational epigenetic inheritance. Nature Reviews Genetics, [online] 23. Available at: https://www.nature.com/articles/s41576-021-00438-5#:~:text=Epigenetic%20change%20can%20arise%20in,arose%20is%20termed%20’intergenerational [Accessed 8 Jul. 2025].

Franklin, T.B., Russig, H., Weiss, I.C., Gräff, J., Linder, N., Michalon, A., Vizi, S. & Mansuy, I.M. (2010). Epigenetic Transmission of the Impact of Early Stress Across Generations. Biological Psychiatry, [online] 68(5), pp.408–415. Available at: https://pubmed.ncbi.nlm.nih.gov/20673872/ [Accessed 19 Jul. 2025].

Gone, J.P. & Kirmayer, L.J. (2020). Advancing Indigenous Mental Health Research. Transcultural Psychiatry, [online] 57(2), pp.235–249. Available at: https://journals.sagepub.com/doi/10.1177/1363461520923151?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed [Accessed 18 Jul. 2025].

Jawaid, A., Roszkowski, M. & Mansuy, I.M. (2018). Chapter Twelve – Transgenerational Epigenetics of Traumatic Stress. [online] ScienceDirect. Available at: https://www.sciencedirect.com/science/article/abs/pii/S187711731830053X.

Matheson, K., Seymour, A., Landry, J., Ventura, K., Arsenault, E. & Anisman, H. (2022). Canada’s Colonial Genocide of Indigenous Peoples: A Review of the Psychosocial and Neurobiological Processes Linking Trauma and Intergenerational Outcomes. International Journal of Environmental Research and Public Health, [online] 19(11), pp.1–28. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179992/ [Accessed 18 Jul. 2025].

McGowan, P.O., Sasaki, A., D’Alessio, A.C., Dymov, S., Labonté, B., Szyf, M., Turecki, G. & Meaney, M.J. (2009). Epigenetic Regulation of the Glucocorticoid Receptor in Human Brain Associates with Childhood Abuse. Nature Neuroscience, [online] 12(3), pp.342–348. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC2944040/#S6 [Accessed 19 Jul. 2025].

Mosby, I. & Millions, E. (2021). Canada’s Residential Schools Were a Horror. [online] Scientific American. Available at: https://www.scientificamerican.com/article/canadas-residential-schools-were-a-horror/.

Pang, T.Y., Short, A.K., Bredy, T.W. & Hannan, A.J. (2017). Transgenerational paternal transmission of acquired traits: stress-induced modification of the sperm regulatory transcriptome and offspring phenotypes. Current Opinion in Behavioral Sciences, 14, pp.140–147. doi:https://doi.org/10.1016/j.cobeha.2017.02.007.

Sabbagh, J.J., O’Leary, J.C., Blair, L.J., Klengel, T., Nordhues, B.A., Fontaine, S.N., Binder, E.B. & Dickey, C.A. (2014). Age-Associated Epigenetic Upregulation of the FKBP5 Gene Selectively Impairs Stress Resiliency. PLoS ONE, [online] 9(9), p.e107241. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC4156438/ [Accessed 18 Jul. 2025].

SAMHSA (2024). Child Trauma. [online] Samhsa.gov. Available at: https://www.samhsa.gov/mental-health/trauma-violence/child-trauma.

Tozzi, L., Farrell, C., Booij, L., Doolin, K., Nemoda, Z., Szyf, M., Pomares, F.B., Chiarella, J., O’Keane, V. & Frodl, T. (2017). Epigenetic Changes of FKBP5 as a Link Connecting Genetic and Environmental Risk Factors with Structural and Functional Brain Changes in Major Depression. Neuropsychopharmacology, [online] 43(5), pp.1138–1145. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC5854813/ [Accessed 18 Jul. 2025].

Yehuda, R. & Lehrner, A. (2018). Intergenerational transmission of trauma effects: Putative role of epigenetic mechanisms. World Psychiatry, [online] 17(3), pp.243–257. doi:https://doi.org/10.1002/wps.20568.