Colonization has long been a way for some nations to gain wealth and influence. The African continent has experienced colonization for more than two millennia. The colonization of what was to become the Americas began in the early part of the 16th century, before which Indigenous Peoples had their own kinship and governance structures, ceremonies and belief systems, as well as knowledge developed over many generations regarding a balanced co-dependent relationship with the land. A degree of cooperation initially existed between Indigenous Peoples and the Europeans who arrived, including the sharing of skills and knowledge, as well as trade and military alliances. Thus, at the outset, relationships with Indigenous Peoples were greatly valued—until they were no longer needed and viewed as an encumbrance. As settler populations increased, their desire for land and wealth grew. The colonization of Indigenous Peoples over several centuries was achieved by guns and by old-world bioweapons that comprised the introduction of smallpox, tuberculosis, and influenza that killed more people than settler bullets did. In fact, in what is now Canada, the Indigenous population pre-colonization was estimated to have been between 350,000 and 500,000 (but some estimates have it as high as 2 million), but declined to just 125,000 by 1867.
In addition to the physical appropriation of land was the colonial effort to eliminate the transmission of cultural identity, traditional skills, and connection to the land. Beginning in 1883 (while this was the date of the first federally established church school, similar institutions existed as early as the 1830s, years before Canadian federation) Indian Residential Schools (IRSs) were established in Canada (as were American Indian Boarding Schools in 1862). Children were forcibly removed from their families and were institutionalized in IRSs with the explicit goal of ‘taking the Indian out of the child’. These mandated church-run IRSs endeavoured to save the souls of the ‘savages’ by immersing them in Euro–Christian beliefs and eradicating access to traditional socialization values, language, practices and ways of life. By the 1930s, roughly 75% of First Nations children attended IRSs, as did many Métis and Inuit children. The last of the IRSs was closed in 1996, but by then several generations of children had experienced the mistreatment that abounded in these institutions.
Colonization as it is recapitulated in current times meets the key criteria of Article II of the UN Convention on Genocide. The intergenerational effects of historic and ongoing systemic racism have had considerable implications for the health and well-being of Indigenous Peoples (Article IIb). Mental health problems are endemic among Indigenous populations; depressive disorders, anxiety, PTSD, and substance use disorders occur at inordinately high levels. In many First Nations and Inuit communities, the occurrence of suicide has been much higher than in the remainder of the Canadian population. The frequency of suicide varies across communities, ranging from 2 to 10 times that of non-Indigenous people, and it is especially disconcerting that over the last two decades suicide has occurred more frequently among young people. This is similarly apparent among American Indians and Alaskan Natives, in whom suicide occurs at 2.5 times the frequency of the population at large.
2. Neurobiological Consequences of Early-Life Trauma
Aside from the psychosocial and environmental factors associated with diminished outcomes emanating from traumatic experiences, numerous biological consequences of chronic and traumatic stressors can contribute to varied psychological and physical illnesses. These
studies, primarily conducted in animal models, have indicated that stressful experiences profoundly affect numerous hormonal processes (e.g., CRH, ACTH, cortisol, estrogen, oxytocin, arginine vasopressin), brain neurotransmitters (e.g., monoamines, GABA, glutamate), neurotrophins (e.g., BDNF, FGF-2, VEGF), brain microglia functioning, and gut microbiota, as well as immune and inflammatory responses that may promote or exacerbate physical and psychological disturbances
[44,78,79][28][29][30]. To a considerable extent, many of these effects are moderated by genetic and epigenetic factors, the organism’s previous stressor experiences, and a constellation of psychosocial and environmental variables
[80][31].
Intergenerational Consequences of Prenatal Stressors
Just as Indigenous children are more likely to encounter ACEs than those who are non-Indigenous, as noted earlier, prenatal challenges (stress experienced by pregnant mothers) are more likely to occur among Indigenous women, with implications for the fetus. In animal models, it has become increasingly apparent that prenatal stressful events may have physical and emotional repercussions that appear in offspring. Like the effects of early-life adverse experiences, it was found that stressors experienced by a pregnant dam influenced the neurotrophins that are fundamental for the neurodevelopment and memory processes, and could thereby promote behavioral disturbances
[92][32]. In humans, stressors experienced during pregnancy may profoundly influence the well-being of offspring. The appearance of low birth weight (which is accompanied by the underdevelopment of brain and body functioning) has been apparent in response to diverse stressful experiences, including wartime conditions, domestic violence, and racial discrimination, as well as in the offspring of mothers that experienced PTSD during pregnancy
[93][33]. Moreover, preterm birth is related to cumulative life stressor experiences, including those encountered prior to pregnancy
[94][34]. The precipitation of preterm birth and low birth weight may occur owing to the provocation of numerous hormonal and inflammatory alterations introduced by stressors
[95,96][35][36].
Individual stressor experiences (e.g., abuse) during pregnancy can have marked effects on the fetus that are manifested as far-reaching postnatal health disturbances. Developmental delays, including emotional and cognitive disturbances associated with variations of limbic and frontotemporal neural networks, have been reported in the offspring of mothers that experience emotional, psychological, physical, or sexual violence during pregnancy
[97,98][37][38]. Commensurate with these findings, such maternal experiences have been linked to altered hippocampal volume and poor social–emotional development in offspring
[99][39]. Likewise, the stress of exposure to natural disasters could affect pregnant women and lead to offspring displaying poorer cognitive, emotional, and behavioral outcomes
[100][40]. In addition to the psychological disturbances engendered by prenatal stressors, these experiences have been associated with childhood immune-related disorders, such as allergies and asthma, and increased susceptibility to infectious diseases
[101][41]. Stressful events experienced prenatally are similarly accompanied by elevated levels of inflammatory factors
[102][42] that favor the subsequent development of chronic diseases, such as type 2 diabetes, heart disease, and some forms of cancer
[44][28].
It is not simply during pregnancy that maternal stress can affect fetal development. Stressors encountered by women prior to becoming pregnant can affect offspring birth weight
[103][43], fetal brain development, and postnatal psychological disorders
[104][44], which could potentially come about due to the distress related to persistent negative rumination. A prospective analysis similarly revealed that preconception PTSD was associated with elevated negativity when children were 3–5 years old, even after controlling for prenatal and postnatal depressive symptoms or sociodemographic factors
[105][45].
3. Epigenetic Changes Related to Stressful Events
Based on
reports t
hat traumatic events
, it could induce intergenerational epigenetic changes among survivors of the Holocaust, as well as those experienced by other groups, it has been suggested that similar actions may affect Indigenous Peoples in Canada and elsewhere
[106][46]. However, data are not currently available that assess this possibility. In part, this lack of research is not surprising given the numerous instances in which Indigenous Peoples have been experimented on without consent, lied to about the goals of research
[107][47], and over-researched while at the same time remaining invisible in research
[108][48]. Moreover, there is a concern that genetic research might be used to undermine the responsibility of colonial governments to acknowledge the causal role of history in relation to health inequities. Thus, while understanding how intergenerational trauma and environmental toxicants can influence epigenetic processes, there is currently an absence of mutually beneficial research addressing these issues among Indigenous people in Canada.
Epigenetic research reflects an understanding that social challenges, environmental agents, and even dietary factors can alter the expression of a great number of genes, without altering the genome itself. Through various processes, the functioning of particular genes can be silenced or activated, which can promote multiple phenotypes
[109][49]. Thus, a history of colonial trauma encountered by Indigenous Peoples may have altered gene expression, leading to elevated vulnerability to psychological and physical illnesses. At one time, it had been assumed that epigenetic actions were infrequent, but it is now known that epigenetic changes are exceedingly common, with some becoming fixed (permanent) whereas others are transient. Childhood abuse, for instance, is accompanied by a great many epigenetic marker beyond those evident among individuals who have not experienced early-life abuse
[110][50]. In view of the numerous epigenetic changes that occur, it is difficult to determine the correspondence between specific changes and particular phenotypes. Moreover, finding such relationships does not imply causality.
The majority
of the resea
rch assessing epigenetic changes has been conducted in animal models, particularly in relation to intergenerational outcomes.
Studies in rRodents have revealed that stressful events can promote epigenetic changes in genes that code for several hormones, neurotrophins and immune factors, which may favor the occurrence of psychological and physical disturbances
[111][51]. Not unexpectedly, poor diet and nutrition similarly influence the expression of genes that can affect well-being. Specific nutrients (or lack of nutrients) may likewise influence the many bacterial species present within the gut and other parts of the body, and alterations of these ‘microbiota’ can produce epigenetic actions, which then promote the development of psychological disorders. Aside from nutrients, microbiota changes can be influenced by other lifestyle factors, stressors, and environmental toxicants, which can influence gene expression and their consequences.
Like other stressors, poor maternal care of pups during early development may promote epigenetic changes that have been linked to hormonal and neurotrophic processes. This includes neglect experienced by pups during early postnatal development, which can affect the epigenetic processes related to the gene regulation of glucocorticoid functioning, which is linked to elevated stressor reactivity
[112][52]. As well, epigenetic actions stemming from early life adversity have been observed in genes associated with diverse behavioral disturbances. These include genes that influence serotonin processes
[113][53], estrogen receptor functioning in the brain
[114][54], as well as neurotrophin activity in several brain regions
[115][55], all of which can affect normal behavioral functioning and the development of psychiatric disorders. In addition to epigenetic changes being provoked by stressful events during early life, similar actions were provoked in rodents stressed during the juvenile period (the equivalent of adolescence in humans); these rodents subsequently displayed increased reactivity and anxiety. Intense stressors experienced in adulthood likewise promote epigenetic effects that influence neurobiological processes linked to depressive-like features
[116,117][56][57].
Among humans, epigenetic changes stemming from ACEs may influence health outcomes. The epigenetic changes introduced by childhood stressors are not restricted to those related to brain processes, having been seen in relation to immune cell functioning and inflammatory factors that could potentially contribute to the appearance or progression of varied diseases
[118][58]. Of course, numerous factors, including genes coding for an array of hormones and growth factors, may contribute to later health disturbances as might an array of experiential and environmental influences (e.g., parental behaviors, poverty).
5.1. Epigenetic Changes Associated with Prenatal Stressor Events
4. Epigenetic Changes Associated with Prenatal Stressor Events
Just as stressors encountered during early life can have long-term ramifications, epidemiological
studiones have indicated that lifestyles of women during pregnancy (e.g., diet and obesity, tobacco and alcohol use), as well as stressful experiences and exposure to air pollutants, are accompanied by epigenetic changes that could affect offspring
[119,120][59][60]. Likewise, psychological stressors experienced during pregnancy can elicit epigenetic changes that influence vulnerability to pathology in offspring, and these actions could be transmitted to subsequent generations
[121][61]. A longitudinal analysis conducted among the offspring of women who were pregnant during Hurricane Sandy in 2012 indicated that when they were 3–4 years of age, they exhibited elevated levels of anxiety and aggressive behaviors, together with increased cortisol levels measured in hair samples. These behavioral and hormonal alterations were accompanied by placental mRNA changes that were tied to endocrine and immune processes
[122][62]. It similarly appeared that, in the offspring of women who experienced a severe ice storm while they were pregnant, cognitive disturbances were subsequently apparent that seemed to be mediated by epigenetic changes linked to genes associated with the promotion of diabetes
[123][63]. Indeed, reprogrammed gene expression within the fetus elicited by prenatal stressors resembled those associated with early-life adverse events
[124][64]. These epigenetic effects could involve actions related to diverse biological processes, and particular attention has been devoted to those that influence or reflect stress reactivity (HPA functioning) and emotionality in offspring
[125][65].
While the phenotypic changes associated with prenatal stressors might have been directly related to epigenetic actions stemming from stressful experiences, they could just as well reflect poor rearing conditions and parental distress and anxiety following a traumatic experience. Based on analyses of offspring that were born following in vitro fertilization, wherein they were biologically related or unrelated to their birth mothers, it was concluded that psychological and cognitive disturbances varied as a function of genetic factors, the prenatal environment, and post-natal maternal factors
[126][66]. In effect, the stress experienced by the biological mother may have contributed to epigenetic changes in offspring, even in the absence of prenatal or postnatal stressors.
5.2. Transgenerational Transmission through Epigenetic Changes
5. Transgenerational Transmission through Epigenetic Changes
While not diminishing the functional consequences of maternal and psychosocial factors, it has been clear
from studi
es in animals that trauma-related epigenetic actions can affect the well-being of offspring across generations. The epigenetic changes brought about by stressors and other environmental exposures can be transmitted from parents to offspring if these alterations occur in germline cells (i.e., sperm or ova) and may occur across several generations, even if further stressors or other experience-dependent changes are not encountered
[127,128][67][68]. Among other factors, exposure to stressors during pregnancy may promote sex-dependent transgenerational effects on anxiety-like behaviors, together with epigenetic changes within genes that code for or influence glucocorticoid receptor functioning and neurotrophins within particular brain regions
[129,130][69][70].
Some of the transgenerational effects of the stressors discovered primarily occurred in males, whereas others were more evident in females. Sex-dependent effects have been assumed to be related to maternal influences, as mothers are the primary caregivers in most rodent species. Several
studiones, however, have suggested that epigenetic outcomes can occur through paternal transmission. Specifically, maternal separation from their male offspring resulted in the pups subsequently exhibiting depressive-like behaviors and increased reactivity to stressors as adults. In the offspring of these males, epigenetically related behavioral and neuroendocrine disturbances were evident, even though they had not come into contact with their male parent
[131,132][71][72]. It was similarly reported that the impact of exposure to a stressor over 6 weeks prior to breeding led to paternal epigenetic effects
[133][73]. Consistent
with studies infor animals, the paternal transmission of epigenetic changes stemming from ACEs in humans was linked to attention problems apparent in their offspring
[134][74]. The early-life stressful experiences of a male parent were similarly associated with altered brain development in neonates, even after controlling for multiple maternal factors
[135][75].
It was similarly demonstrated that early-life paternal challenges that comprised a series of different stressors could engender behavioral disturbances that were evident up to the fourth generation of offspring
[136][76]. Effects such as these have been attributed to epigenetic actions that are especially notable among stress-reactive mice, pointing to the fundamental importance of individual difference factors in predicting the transmission of stressor effects over generations. As well, the intergenerational effects of stressors are determined by the characteristics of the stressor experienced (e.g., social versus asocial stressors; acute versus chronic stressors) and the age of the animal at the time of stressor exposure
[137][77].
Predictably, far fewer
studies have assessed the intergenerational and transgenerational effects of stressful experiences in humans. The length of time for each generation to come to the age of having children has limited the research regarding the intergenerational effects of trauma. Even when
studiesit were conducted to assess the transmission of stressor effects across generations, it was uncertain whether the effects observed were related to the trauma experiences, given that they were assessed retrospectively. Moreover, most complex psychological and physical disorders are mediated by multiple genes whose actions can be moderated by numerous psychosocial and experiential factors, making attributions to epigenetic changes and intergenerational outcomes tenuous. Nonetheless, an array of factors related to stressors have been identified that are subject to epigenetic changes, some of which might be relevant to intergenerational outcomes.
Epigenetic changes in genes associated with glucocorticoid functioning have been observed in relation to aging, as well as stressor experiences
[138][78], and it has been found that aging and stressor actions are synergistically linked in affecting pathology and inflammatory processes
[139][79]. Adverse childhood events are similarly tied to epigenetic changes that are associated with brain changes relevant to both executive functioning and adult depression
[140][80]. Moreover, among individuals with a history of childhood abuse and neglect who had died by suicide, epigenetic changes were present within the genes of the glucocorticoid receptors within the hippocampus
[141][81].
The intergenerational effects of traumatic events have been examined more extensively among survivors of the Holocaust than among other groups. The survivors frequently displayed elevated glucocorticoid functioning in response to stressors
[142[82][83][84],
143,144], and such effects were frequently apparent in the adult offspring of Holocaust survivors. These behavioral and hormonal alterations were, in many instances, accompanied by epigenetic changes in both the survivors and their children
[145][85], varying in relation to whether one or both parents had been survivors, as well as whether one or both parents had developed PTSD
[146][86]. These data imply neither causal nor direct connections between particular epigenetic effects and any specific phenotypic changes, especially as the latter may be mediated by parental mental health problems and disturbed parenting styles
[147][87]. Importantly, offspring might not ordinarily present with disturbed day-to-day behaviors, but the actions of epigenetic changes might be most evident upon encounters with further adverse events
[148][88].
As alluded to earlier, the intergenerational epigenetic changes associated with stressors were not unique to Holocaust survivors. Many women who experienced extreme abuse (sexual violence, torture) during the Kosovo war developed PTSD during pregnancy, and epigenetic changes were detected in their children, including those that coded for a glucocorticoid receptor and a serotonin receptor, as well as a neurotrophin
[149][89]. Paralleling these findings, the children of pregnant women who developed PTSD during the 1994 Tutsi genocide subsequently displayed increased epigenetic changes tied to glucocorticoid receptor levels relative to those apparent in women that had not been exposed to the trauma
[150][90]. The presence of an epigenetic marker related to the oxytocin receptor has also been associated with changes in discrete brain regions related to altered empathy in mothers
[151][91], and could affect parent–offspring interactions.
Epigenetic changes do not only occur as a result of psychosocial stressors. Environmental toxicants and drugs consumed during pregnancy may promote teratogenic effects in a developing fetus, and epigenetic variations can similarly be engendered in the fetus by environmental challenges. Endocrine-disrupting compounds, such as phthalates and bisphenol-A, as well as pesticides and dioxins, can promote epigenetic changes that are transmitted to the next generation of rodents, thereby increasing health risk
[152][92]. Pesticides and fungicides can similarly promote epigenetic changes that increase vulnerability to viral challenges, and these actions can be transmitted transgenerationally
[153,154][93][94]. Paternal intergenerational effects have been implicated with epigenetic changes associated with nutrients consumed and with deficiencies in folic acid
[155][95]. Likewise, epigenetically transmitted actions related to paternal diet (high fat or low protein) are associated with risk of disease in offspring
[156][96]. Given that stressors can affect nutrient intake, it can reasonably be expected that intergenerational effects can be transmitted indirectly by a male parent.
Lasting epigenetic changes have been reported among individuals that were born during severe famine conditions. Near the end of the Second World War, towns in the western parts of the Netherlands that had been occupied by Nazi forces were prevented from obtaining food or fuel, leading to misery and starvation. Children born during this period, referred to as the Dutch Hunger Winter, subsequently presented with elevated heart disease and the risk of type 2 diabetes. Psychiatric disturbances such as schizophrenia and depression occurred more often, and poor cognitive performance was apparent in later life
[157][97]. The experience of the Dutch Hunger Winter was associated with genetic changes that influenced birth weight and subsequent LDL cholesterol levels
[158][98]. Moreover, analyses conducted decades after this famine indicated that individuals who had prenatally experienced this condition expressed epigenetic changes related to factors that may have disposed individuals to type 2 diabetes
[159,160][99][100].
Data collected in a different context are consistent with those obtained from
studiones of the Dutch Winter hunger. Specifically, among children born during the Great Chinese famine (1959–1961) the risk for adult type 2 diabetes was elevated and this outcome could have been transmitted across generations
[161][101] (Li, 2017). Likewise, early-life differences in famine conditions within two regions of China revealed differences in epigenetic changes associated with neurotrophins, together with changes in cholesterol levels
[162][102]. The intergenerational impact of the Holodomor genocide of 1932–1933, when Ukraine experienced a famine created by policies created by Stalin, is another
csitua
setion in point
[5][103]. The constellation of behaviors associated with famine (or food insecurity) has been described as living in ‘survival mode’, including horror, fear, mistrust, sadness, shame, anger, stress and anxiety, decreased self-worth, stockpiling of food, reverence for food, overemphasis on food and overeating, inability to discard unneeded items, indifference towards others, social hostility, and risky health behaviors. However, the imposition of such conditions and their implications have not been addressed in relation to Indigenous Peoples, despite the high levels of food insecurity in many Indigenous communities.
In view of the multiple epigenetic changes that have been associated with distressing events and with diverse psychological problems, as well as the influence of numerous psychosocial factors, it is premature to point to a single epigenetic alteration as being responsible for pathological outcomes stemming from adverse events. Many epigenetic actions have been identified among individuals who experienced stressful events during early life
[117][57]. The involvement of these epigenetic changes in the intergenerational effect of stressors remains to be fully evaluated, but the findings are certainly in line with the view that actions other than, or in addition to, those associated with glucocorticoids may contribute to the persistent actions of early-life adversity. More extensive prospective analyses concerning the emergence of pathological conditions, together with whole epigenome analyses, could point to clusters of epigenetic markers relevant to the concatenation of factors that link generations of historical trauma exposure to illness occurrence.
Being subjected to collective trauma has long-term intergenerational consequences that are instigated through multiple psychosocial and neurobiological mechanisms. Nonetheless, resilience in the aftermath of such challenges does occur. Resilience is fostered when the survivors of natural events are able to express and anticipate collective solidarity and cohesion, and act cooperatively to draw on collective social support resources
[163][104]. Processes that ground people in an identity, self-affirmation, belonging, and safety
[164][105], and are further imbued with spirituality can serve to promote continuity of relationships across generations
[165][106]. In effect, intergenerational resilience can be derived from the symbiotic relationship to the land, encompassing physical and non-physical elements, such as the social, emotional and spiritual aspects that provide the foundation of identity, social connectedness, and a sense of community and belonging
[166,167][107][108].
With so many factors playing into the compromised well-being of Indigenous Peoples, multiple issues need to be addressed concurrently to bring about meaningful change. The challenges that Indigenous Peoples continue to encounter, ranging from community infrastructure (housing, clean water) to food security and quality, along with access to appropriate health services, need to be addressed now. Rather than applying singular or isolated solutions emanating from Western mental health frameworks, what is needed is to enable Indigenous Peoples to identify and implement culturally relevant strategies that reflect the connections between individuals and their social, cultural and environmental contexts. Indigenous Peoples are reclaiming their inherent rights to self-determination and reconnecting to their cultural roots, including renewing land-based values, skills, and spiritual connections among the next generation of young people. Indigenous understandings of wellness are inherently holistic, with resilience emanating from the adaptive balance of protective and risk factors over time and space
[197][109]. This may provide the perspective needed to counter the centuries of genocidal actions targeted against them.