User:Caresse.Nguyen/Transgenerational trauma

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Transgenerational trauma is the psychological and physiological effects that the trauma experienced by people has on subsequent generations in that group. There are two types of transmission: intergenerational transmission whereby epigenetic changes are passed down from the directly traumatized generation [F0] to their offspring [F1], and transgenerational transmission when the offspring [F1] then pass it down to their offspring [F2] who have not been exposed to the initial traumatic event. Exposure includes when the offspring is in utero.

Collective trauma is when psychological trauma experienced by communities and identity groups is carried on as part of the group's collective memory and shared sense of identity. For example, collective trauma was experienced by Jewish Holocaust survivors and other members of the Jewish community at the time, and by the First Native Peoples of Canada during the Canadian Indian residential school system. When this collective trauma affects subsequent generations, it is called transgenerational trauma. For example, if Jewish people experience extreme stress or practice survivalism out of fear of another Holocaust, despite being born after the Holocaust, then they are experiencing transgenerational trauma.

Transgenerational trauma can be a collective experience that affects groups of people who share a cultural identity (e.g., ethnicity, nationality, or religious identity). It can also be applied to single families or individual parent–child dyads. For example, survivors of individual child abuse and both direct survivors of the collective trauma and members of subsequent generations individually may develop complex post-traumatic stress disorder.

The mechanism for transmission of trauma may be via epigenetic modifications introduced by stress. This is a novel area of research and given the complexity of issues surrounding trauma and the human experience, the relative contributions of epigenetics, cultural, and social factors will be challenging to elucidate.

Historical trauma
Historical trauma, a sub-type of transgenerational trauma, is the collective devastation of the past that continues to affect populations in the present through inter-generational transmission. Historical trauma results in vulnerability to mental and physical health problems due to ancestral suffering which has been collected throughout generations into “legacies of disability for contemporary descendants”. Although the actual traumatic event and affect group(s) are heterogeneous, all historical traumas consist of three elements: a traumatic event, a resulting collective suffering, and a multigenerational impact of that trauma. Over time the trauma and relationship to the victims typically evolve in a similar but more complicated way to genetic anticipation, resulting in a greater loss of identity of the victims and further integration into society.

For individual victims, historical trauma often manifests in 4 ways: depression, hyper-vigilance, traumatic bond formation, and reenactment of the trauma. Building upon the clinical observations by Selma Fraiberg, child trauma researchers such as Byron Egeland, Inge Bretherton, and Daniel Schechter have empirically identified psychological mechanisms that favor intergenerational transmission, including dissociation in the context of attachment, and "communication"[ clarification needed] of prior traumatic experience as an effect of parental efforts to maintain self-regulation in the context of post-traumatic stress disorder and related alterations in social cognitive processes.

Transmission during pregnancy
Main articles: Transgenerational stress inheritance and Epigenetics of anxiety and stress–related disorders

Stress can be biologically transmitted across generations through the uterine environment. Intrauterine development is not only critical for traditional organ/fetus development but also sets the stage for neural and behavioral development. Exposure to harmful stimuli during this stage can have long-lasting, detrimental effects. The uterine environment with its unique blend of the mother's cellular secretions and proteins is a major source of stimuli. Empirical evidence has shown that trauma experienced by a mother during pregnancy can affect offspring's physiology and psychology. Trauma and stress during this stage are associated with an increased risk for the development of neuropsychiatric disorders such as depression and anxiety. The increased risk of these psychiatric disorders has been linked to changes in DNA expression due to epigenetic alterations in DNA methylation patterns.

Research shows that epigenetic changes can be observed in genes associated with the hypothalamic-pituitary-adrenal (HPA) axis, which coordinates the body's stress response system. The glucocorticoids, including cortisol, are neurohormones triggered by stress which trigger the "fight-or-flight" response which includes increased blood pressure and heart rate. NR3C1 is a gene that codes for glucocorticoid receptors. In rodent studies, it was found that the pups born to neglectful mothers showed increased methylation in the NR3C1 gene compared to those with high grooming mothers. Increased expression of this glucocorticoid receptor due to demethylation of the gene leads to a decrease in the offspring's stress response. Pups born to a low licking and grooming mother but raised by a high licking-grooming mother had less NR3C1 gene methylation thus lower stress levels. This shows that maternal grooming behavior is responsible for the changed methylation state of the glucocorticoid receptor. Findings show that the grooming is linked with demethylation of the NR3C1 gene, which increased glucocorticoid receptor expression resulting in decreased stress levels in the mice. These cross-fostered pups were found to be indistinguishable from the pups born and raised by neglectful mothers or high grooming mothers.

The uterine environment of the offspring is a critical factor in development and epigenetic modification. Hormones such as leptin and insulin, as well as nutrients, trigger the regulation of amino acid transporters in the placenta. Amino acid transport is necessary for fetal growth, and its restriction can have life-long effects on the offspring’s health. Amino acid transport is also regulated by DNA methylation of amino acid transporter genes, modifying their expression in the placenta throughout the fetus's development.

There have been multiple animal studies reporting the link between adverse childhood experiences and epigenetic modifications. Although, these studies were in animal models, they study epigenetic mechanisms that may occur in humans. Three of those and their findings are mentioned below: Similar to the study above, reduced methylation of the glucocorticoid receptor gene was found in the offspring of high-licking canine mothers. In contrast, offspring that face early adversity exhibit endocrine dysregulation, as well as reductions in neuronal plasticity in the prefrontal cortex (PFC) that persist into adulthood. Another study provides evidence of increased methylation of stress-response genes including brain-derived neurotrophic factor and nuclear protein phosphate-1 in neurons in rats who exhibit PTSD-like behavior. And one particular study, McGowan et al., the “subject group was suicide completers, which reported that childhood abuse was associated with greater methylation levels at CpG sites in the exon1F of the promoter region of the glucocorticoid receptor gene.” This study examined epigenetic modifications in neurons but did not provide insight into links of adverse childhood experiences and epigenetic modifications.

In animal models, maternal stress and trauma during pregnancy has been shown to reduce the expression of placental enzyme 11B-hydroxysteroid dehydrogenase type 2 (11 β-HSD2), which converts the mother's cortisol to inactive cortisone. This leads to increased fetal exposure to the mother's glucocorticoids, which affects the development of glucocorticoid-sensitive systems like the HPA axis. In some studies, abnormal cortisol levels compared to controls and alterations in DNA methylation were observed in infants of mothers who endured trauma while pregnant, particularly in the NR3C1 glucocorticoid receptor gene.

There are questions of whether transmission occurs via maternal care or in utero changes, or perhaps both. A study by Alhassen et al. found that mothers who were exposed to a predator’s scent, thus inducing stress, were more likely to rear pups who expressed depressive-like behaviors and social deficits. However, non-traumatized mothers’ maternal care was not sufficient enough to reverse prenatal trauma-induced behavior.

Trauma-induced behavior in female mice mothers was also linked to changes in the brain metabotranscriptome of their offspring, which were significantly different from the pups from mothers who did not experience trauma. The study finds that a large upregulation in 2-hydroxyglutaric acid in pups and adults exposed to trauma prenatally induces changes in epigenetic mechanisms and mitochondrial function. In their model, 2-hydroxyglutaric acid is upregulated due to hypoxic conditions prenatally, as the mother during her fight-or-flight response has less oxygen delivered to the pups. Researchers were able to counteract long-term intergenerational trauma-induced depression using acetyl-L-carnitine, which counteracts the prenatal modifications in many mechanisms which stem from hypoxia.

Research has also been conducted on mothers who were pregnant on 9/11. Cortisol levels between pregnant mothers who did not develop PTSD due to the event versus pregnant mothers who did develop PTSD indicate that the latter group had a decrease in cortisol levels. Furthermore, children of these mothers who developed PTSD also had lower cortisol levels. Low cortisol is previously known to increase the risk for PTSD, so the fact that both mother, after traumatic exposure, and the child, presumably due to maternal stress levels, had lower cortisol suggests some sort of epigenetic modification to cortisol levels was made during the traumatic event that was able to be passed down. It was also found that children whose mothers lived close to the World Trade Center had higher levels of stress agents in their saliva. Altogether these studies suggest an intergenerational transmission of trauma that creates a higher susceptibility to PTSD in the child due to lower cortisol levels. The development of PTSD due to parental PTSD was also studied in adult offspring of Holocaust survivors. Here, researchers also found a link between enhanced suppression of cortisol found via urinary samples and saliva samples and parental PTSD.

The fetal environment is influenced by the maternal diet. This environmental history can cause the fetal developmental response to change to produce a metabolic phenotype that suits the anticipated environment.

Epigenetic effects of nutrition include the methylation of genes involved in energy metabolism, anti-inflammatory processes, and tumor suppression. Studies examine gestational diabetes mellitus (GDM), a condition where the mother experiences insulin resistance during pregnancy to avoid low blood glucose levels. This is a response to the shift of nutrients from the mother to the fetus. GDM results in maternal hyperglycemia, fetal hyperinsulinism, and fetal overnutrition.

Epigenetic Mechanisms
DNA methylation can act as the mechanism for the transmission of intergenerational trauma. Methylation typically takes place at relevant CpG islands and maintains its transcriptional repression effect across cell divisions, but can also be dynamically regulated. DNA methylation has been found to be significant in regulating fear memory via methylation of immediate early genes (IEGs) in the hippocampus dentate gyrus of mice models.

Histones can be modified via acetylation, methylation, phosphorylation, and SUMOylation. Acetyl and phosphate groups, which are modifiers typically associated with an upregulation of gene expression, attach onto lysine, serine, threonine, and tyrosine residues of histones. Methylation (on lysine or arginine residues) and ubiquitylation (on lysine residues of histones H2A and H2B) are associated with both activating and repressing genes. SUMO stands for small ubiquitin-like modifier and it binds to lysine residues. SUMOylation is widely associated with repression and is also typically found with other epigenetic modifiers. These histone modifications alter the structure of chromatin, thus affecting the transcription of the genes associated with the altered histones. Many post-translational modifications are affected by acute and chronic stress via glucocorticoid cascades.

Another pre-clinical study finds that the use of histone deacetylase inhibitors can aid in "exposure-based approaches in anxiety and trauma therapy". Histone deacetylase inhibitors block the deacetylation of histones, which then allows genes to remain active by preserving the active acetyl mark on the histone on the DNA. In the context of anxiety and trauma therapy, this allows the preservation of a long-term extinction memory that is able to replace the traumatic memory. Histone deacetylase inhibited the formation of an extinction memory which consequently preserved the fearful memory, and by inhibiting it individuals in exposure therapy are able to create new memories with harmless or safe associations to their traumatic memory.

Non-coding RNAs, or ncRNAs, have been seen altering gene expression and being responsive to traumatic stress. miRNAs, or micro RNAs, can be used to silence genes via the RISC complex. They are able to degrade mRNA targets thus repressing translation of a gene. In PTSD studies, miRNAs were found to be involved in responding to trauma. Some evidence also supports long non-coding RNA, lncRNA, and PIWI-interacting RNA, piRNA, being affected by trauma.

Post-transcriptional RNA modifications are generally known to alter the folding of RNA as well as their affinity for complementary strands. Not much is known about it and its role in altering gene expression post-trauma, but there has been evidence of contextual fear conditioning altering FTO mRNA, that encodes an RNA demethylase. This suggests RNA modifications may have been altered in response to this fear conditioning and may play a role in altering gene expression in response to trauma.

Native/Indigenous Peoples of the Americas
Settler-Colonization encompasses a wide range of practices: war, displacement, forced labor, removal of children, relocation, destruction massacre, genocide, slavery, unintentional and intentional spread of deadly diseases, banning of indigenous language, regulation of marriage, assimilation, eradication of culture, social and spiritual practices. For more than 400 years European colonization has violently subjugated the indigenous peoples of the Americas through ethnic cleansing, forced assimilation, and acculturation. The genocide perpetrated by the U.S. government through Indian reservations, and harmful policies excluding and oppressing Natives evoked similar responses to trauma as the descendants of Holocaust survivors. In a similar way we find transgenerational trauma in Holocaust survivors we find the same patterns and effects in Indigenous populations and their children and grandchildren. Settler colonization has been recognized as a contributing factor to the ill health of indigenous populations around the world. Ill health is linked to epigenetic mechanisms.

Due to the effects of settler colonialism, oppression, racism, and other aversive events, Native Americans disproportionately experience adverse childhood experiences as well as health disparities, including high rates of posttraumatic stress, depression, substance abuse, diabetes, and other psychiatric disorders. There is evidence that these adverse childhood experiences have been linked to methylation changes in genes that regulate the stress response (HPA axis). These molecular changes contribute to health disparities.

The mechanisms and causality of historical trauma are heterogeneous and complex. Social, cultural, economic, and genetic mechanisms are intertwined in a complex manner. This results in significant hurdles in elucidating the mechanisms and relative magnitude of causal effectors. However, epigenetic mechanisms, via modification of gene expression, are known to play a role.

Criticisms
“Time, trauma, and the brain: How suicide came to have no significant precipitating event” published in June of 2021 by Stephanie Lloyd and Alexandre Larivée discusses the framing with which we have and continue to discuss trauma and its consequences within scientific communities. Particularly with the research done in epigenetics, trauma has been reframed as biochemical deviations from a perceived normal individual due to a traumatic event which then put individuals at higher risk for symptoms of trauma, such as high stress. Deviations from supposed normal and healthy levels are seen as deficits and dysfunctions, further decentering the individual's consciousness and highlighting their ailing body. These observations underline how the definition of trauma has shifted and changed with time and now is hyper-focused on the body's supposed deficits and predispositions rather than the individual's consciousness and experiences.