Epigenetic Changes in Transgenerational Trauma and Potential Reversibility
Through Psycho-Spiritual Interventions
Kayla Mann
Southern New Hampshire University
In the last decade, epigenetics has taken center stage in connecting the relationship between stress exposure, health and behavior (Kaliman, 2019). “Acquired or inherited epigenetic changes modulate gene expression states without modifying the DNA sequence itself, they can be long-lasting, yet, they are potentially reversible” (Kaliman, 2019). The topic I chose to research is whether or not trauma can be passed down through genetics to offspring and if psycho-spiritual interventions can assist in reversing epigenetic changes, therefore preventing trauma responses from being passed through generations.
Three important mechanisms of epigenetic changes that will be discussed are: DNA methylation which is the addition of methyl groups to cytosine/guanine (CpG sites) on the DNA sequence which causes condensation of chromatin, causing DNA transcription to become silenced or unexpressed (Venditti et al., 2020). Acetylation and deacetylation which is when histones loosen and tighten chromatin, respectively, thus creating “open” or “closed” domains of gene activity along the genome (Venditti et al., 2020). Finally, microRNAs control the stability and access of mRNAs to translate protein formation and this is the process that is influenced with epigenetic changes (Venditti et al. 2020).
Literature Review
Transgenerational trauma: The role of epigenetics by Krippner & Barrett (2019) made claims that the effects of trauma have caused epigenetic changes in phenotype (observable) genetic expression. The effects of trauma on offspring have previously been assumed to be passed on through behavior, however, research shows that trauma can cause epigenetic changes that are then inherited. Evidence also shows there is an interconnection between both epigenetic changes and behavioral reinforcements from the environment.
One example was a study on mice in which the smell of cherry blossoms were paired with a shock to the foot (Dias & Ressler, 2014 as cited in Krippner, 2019). The mice and their offspring were studied after these conditioned responses were formed. It was found that the offspring of the mice from multiple generations from the initial experiment were conditioned to have a startle response to the smell of cherry blossoms. Another study which experimented with the maltreatment of infant rats, Roth et al. (2009), found that both the infant rats and their future offspring displayed methylation of the brain-derived neurotrophic factor (BDNF) gene in the prefrontal cortex, providing further evidence for the intergenerational epigenetic transmission of stress (Roth et al., as cited in Lucero, 2018).
Furthermore, research has found that nurturing care turns on genes in the brain that regulate stress, making offspring social, curious, and confident while neglect produces distressed, fearful offspring (Meaney, 2001 as cited in Lucero, 2018). Lucero continues to show evidence of epigenetic changes in the stress responses where it was found that rat pups who received less maternal care displayed increased NR3C1 gene methylation, which is responsible for encoding the glucocorticoid receptor in the hippocampus (Weaver et al., as cited in Lucero, 2018). “Altered glucocorticoid receptors have rippling developmental effects on the stress response system (including cortisol circulation), metabolism, immune function, and cognitive function (De Bellis and Zisk 2014; Keating, 2016, as cited in Lucero, 2018).
In the article, ‘Epigenetic Alterations Associated with War Trauma and Childhood Maltreatment’, researchers found that epigenetic changes were observed in the hypothalamus-pituitary-adrenal axis & the immune system of survivors of childhood and adult trauma (Ramo-Fernandez, Schneider, Wilker, & Kolassa, 2015). In this article, research was reviewed that looked at the differences between the epigenetic changes in either adult war exposed victims or childhood maltreatment. They found supporting evidence to show DNA methylation which affects biological stress responses of people with severe trauma. It was also claimed that transgenerational epigenetic DNA methylation responses showed the greatest transfer to offspring either in utero or closer to early development and its associated genetic transmission is passed through the germline cells.
In the literature review by Ramo-Fernandez et al., DNA methylation was found to be involved in memory storage associated with PTSD and showed inhibitory effects in consolidation of memory in rat hippocampi (Miller & Sweatt, 2007 as cited in Ramo-Fernandez et al., 2015). PTSD is characterized specifically by intrusive memories and the inability of the brain to translate and consolidate them. There were significant differences found with the expression of the glucocorticoid receptor gene (NR3C1) between childhood maltreatment trauma and war trauma in which it was found that there was a hyper or hypo-gene expression, respectively (Ramo-Fernandez et al., 2015). DNA methylation changes in the lymphocytes and cortisol levels of war combat veterans with PTSD were found which connect the links between PTSD and health related trauma responses (Smith et al., 2011 as cited in Ramo-Fernandez et al., 2015).
It was found through a study on rats that the most significant effects of epigenetic changes and transgenerational effects happen in the earliest stages of life. It has been found in multiple studies that DNA methylation of germline cells have the most potential to pass profound consequences of behavioral and endocrine disruptions to stress response onto offspring. It was also noted that the transmission of epigenetic changes are typically buffered in a germline cell reset period where the effects of epigenetics may not be transmitted if prenatal and postnatal conditions are stable.
In the article, ‘Glucocorticoid receptor gene (NR3C1) methylation during the first thousand days: Environmental exposures and developmental outcomes’, Berretta, Guida, Forni & Provenzi (2021) claim that the first 1000 days from conception are the most significant for the possibility of epigenetic transgenerational trauma transmission. They reviewed 34 research studies where it was found that increased methylation of the NR3C1 gene may be consistently associated with a variety of stressors occurring in the first 1000 days (Berretta, Guida, Forni & Provenzi, 2021).
However, this study found a variety of weak associations between early stress exposure from the mother and long term effects of psychiatric symptoms. This review, which was conducted in 2021, found conflicting evidence that may destabilize previous claims about the associations between NR3C1, DNA methylation and behavior. This points to the possibility of a greater effect from caregiver behaviors and parenting style on epigenetic effects passed down to offspring. This states that the potential for the modulating effects of the germline cell reset period may decrease transmission of epigenetic changes through biology, but may later become reinforced by the behaviors of parents. This would therefore recreate the epigenetic stress-trauma responses which did not get passed down through genetics, but are now environmentally inherited. This is substantial information for professionals to advocate for social service interventions to assist in better parenting skills. This research can lead professionals in the field to focus more attention to helping parents in the early stages of raising children.
The article, ‘Epigenetics and meditation’ by Kaliman (2019) analyzed four research studies on the epigenetic effects of meditation and its ability to reverse epigenetic changes from stress responses. All four studies showed epigenetic changes with meditation interventions which affect biological processes. Findings throughout the studies found that particularly in long term meditators, the epigenetic effects of reducing stress & aging responses were significant. Decreases in DNA methylation were found which provides evidence to support the research question of whether or not psychological or spiritual interventions can reverse negative epigenetic changes. These results support the hypothesis that psycho spiritual interventions may decrease epigenetic trauma responses from being passed down to offspring, both biologically and behaviorally. It was also found that DNA methylation changes were observed in response to cognitive behavioral therapy and social support (Keers et al., 2015, Brody et al., 2016, as cited in Kaliman, 2019).
The next article that was reviewed was an experimental research study titled ‘Methylation of FKBP5 and SLC6A4 in Relation to Treatment Response to Mindfulness Based Stress Reduction for Posttraumatic Stress Disorder’ by Bishop et al. (2018) which included 22 participants, all veterans diagnosed with PTSD. 11 of the participants were responders (had a significant change in symptom scores) to the Mindfulness Based Stress Reduction (MBSR) interventions and 11 of the participants were non-responders. Participants were part of a 9 week treatment intervention during the study. This study assessed methylation levels at CpG sites in regions of the serotonin transporter (SLC6A4), which was previously associated with expression and depression outcomes. The study also assessed the Intron 7 region of the FK506 binding protein 5 (FKBP5) containing known glucocorticoid response elements (involved in the hypothalamic-pituitary-adrenal axis) suggested to regulate this gene (Bishop et al., 2018).
There were no significant changes in the methylation of SLC6A4, however, there were significant changes in the methylation of FKBP5. The researchers hypothesized that a decrease in methylation would be associated with better responses to treatment (Bishop et al., 2018). Their research found that the responders to MBSR “had an increase in methylation and non-responders had a decrease in methylation from before to after treatment” in the FKBP5 intron 7 region. “Increases in FKBP5 methylation after treatment in responders as compared to decreases in non-responders suggest that effective meditation intervention may be associated with stress-related pathways at the molecular level. The preliminary findings suggest that DNA methylation signatures within FKBP5 are potential indicators of a response to meditation treatment in PTSD and require validation in larger cohorts” (Bishop et al., 2018).
These findings by Bishop et al. 2018 show changes in DNA methylation, however, are inconclusive to the implications for treatment. As the results were not as they had hypothesized due to finding increased DNA methylation in participants who had better treatment responses to MBSR. However, it does give evidence of a response. This response of the FKBP5 gene can give future researchers a marker within the path of trauma responses and the possible reversibility of epigenetic changes from mindfulness based interventions.
Next, the article titled ‘Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators’ by (Kaliman et al., 2014) was reviewed. This was an experimental study to analyze the epigenetic effects of meditation with 40 participants who had similar demographics. 19 were in the treatment group who completed an 8 hour meditation retreat who were long term meditators of 3 or more years. 21 were in the control group who engaged in leisurely activities within the same environment who did not complete the meditation retreat. After the brief intervention they detected reduced expression of histone deacetylase genes (HDAC 2, 3, and 9), alterations in global modification of histones (H4ac; H3K4me3) and decreased expression of pro-inflammatory genes (RIPK2 and COX2) in meditators compared with the control group (Kaliman et al., 2014). This study supports the hypothesis that psycho-spiritual interventions affect epigenetics. It shows evidence of epigenetic changes from spiritual mind body practices which may decrease the potential to pass trauma responses to future generations.
‘Molecules of Silence: Effects of Meditation on Gene Expression and Epigenetics’ by Venditti et al. (2020) was analyzed. This article states that one key feature of epigenetic information is its potential reversibility. Evidence has been found to support DNA methylation changes, as well as increases in histone acetylation with meditation (Venditti et al., 2020). The research reviewed in this article shows evidence to support epigenetic changes associated with meditation, yoga, tai chi and other mindful based practices/interventions. Results showed that, in both long and short term practitioners of mindful based interventions, differential transcription occurs in genes involved in metabolism, inflammatory processes, oxidative stress, and DNA damage responses (Venditti et al., 2020).
“The first cross-sectional study, by Ren et al. (2012) analyzed the epigenetic effects of Tai Chi on the methylation of 66 sites using saliva samples from experienced practitioners. They observed that 6 CpG sites on different chromosomes showed significant differences between the trainees and controls” (Venditti et al., 2020). “A similar cross-sectional study was conducted by Harkess et al. (2016) who focused on the CpG methylation levels of candidate genes involved in immune function, namely, TNF, IL-6, and CRP, in blood samples of chronically stressed women practicing Yoga, compared to a waitlist group. Their main result was that Yoga was associated with hypomethylation of the TNF gene while IL-6 and CRP appeared unaffected. Interestingly, the same results were observed when the waitlist group later participated in the Yoga intervention” (Venditti et al., 2020).
Technology
The advancement of genetic databases which can hold the maps of the human genome have been paramount in the advancement of studying the effects that trauma has in transgenerational transmission of epigenetic changes. Microscopes, tissue extraction, advancement in animal studies and the accumulation of prior knowledge on genes & human behavior have allowed researchers to acquire increasing evidence to support the plasticity of genetics.
Historical Views
The views on this topic seem to have stayed relatively stable and the articles that have been reviewed all support each other’s findings. Each article supports the earlier research and the specific findings are generally consistent which provides stronger evidence for the initial claims. Later studies have begun to show evidence that points to an increased behavioral effect on epigenetic changes rather than directly inherited changes, again pointing to the complicated connection between nature & nurture.
Conclusions in Biopsychology
The conclusions that can be drawn from this literature review are that the effects of transgenerational transmission of trauma and genetic changes occur from around conception through the first 2 years of life. Genetic and behavioral effects are interwoven and move together. Epigenetic changes can be passed down, however, they go through a potential reset period at gestation in connection to the germline cells. This may prove to buffer some of the inherited transmissions of trauma. It was found that if high levels of stress or trauma is occurring during this pivotal first 1000 days from conception that the epigenetic stress responses are more likely to be passed down biologically. This still shows the entanglement between biological functioning, behavior and the environment. Within either nurture or nature, it is agreed that the first 1000 days from conception are the most important to prevent inherited trauma responses. Understanding these results should make families consider the importance of this time in health, stress reduction and time spent nurturing their children. It is my hope that families will make the appropriate arrangements to provide the best environments for their offspring.
Literature Review and Design in Research
Many of the studies reviewed were literature reviews that analyzed current research within the field of epigenetics and trauma. Some of the designs used experimental methods that included participants with diagnoses of PTSD, adverse childhood experiences (ACEs) or chronic stress. In the experimental designs, DNA samples were taken from blood, saliva, placenta, or cord blood to study a variety of age ranges. Experimenters had participants complete meditation interventions or mind body treatment programs in which DNA samples or symptom scores were taken before and after the interventions.
Ethics
In the various studies that were reviewed many research methods used animal studies to maintain ethical standards for studying the application of potentially harmful psychological reactions. Ethics were addressed by conducting experiments on mice or rats. The ethical guidelines for animal studies are more liberal which allow researchers to conduct potentially harmful studies on animals rather than humans. Since animals have similar brain functions and behavioral responses, the information from experimentation can be implied to similar results occurring in humans without conducting experiments that would likely cause psychological or physical harm to humans. The benefits to humans for animal studies to be conducted must be significant enough to assist humans with their psychological maladies.
In humans, they took non-invasive data collected by blood draws or observation of tissue cells from participants who had been natural trauma survivors. The researchers adhered to ethical standards by only taking samples of tissues, saliva, blood, placenta, buccal cells or cord blood of participants. This method did not apply any harmful psychological experimentation onto the subjects but studied the effects of the inclusion criteria.
Hypothetical Research Design
Gap Statement
After reviewing the literature on the initial research question that asked: can trauma be passed down through genetics to offspring and can psycho spiritual interventions assist in reversing epigenetic changes, therefore preventing trauma responses from being passed to offspring; a few gaps were identified. There was significant evidence to support the theory that trauma is passed down through epigenetic changes through generations. Biologically, it was found that epigenetic trauma responses were inherited specifically within the first 1000 days from conception. If not passed biologically through the germline cells or in utero, trauma could be passed through behavioral & environmental factors which then create secondary epigenetic changes.
The next segment of the research question asked, can psycho-spiritual interventions, such as meditation or intensive therapy catalyze a reduction in the biological trauma-stress responses? There was evidence to support epigenetic changes correlated to meditation, however, some of the information was inconclusive. The following research gaps were found in 1). The number of participants included in previous research studies had a smaller sample size 2). There were limited studies conducted with people who were new to meditation who also fit the inclusion criteria for significant mental-emotional distress, ACEs, or PTSD 3). There was limited research found on the possible epigenetic effects of meditation for new practitioners, which changes were significantly found in long term meditators 4). Studies found inconclusive evidence for epigenetic biomarkers in FKBP5 methylation which showed results that were ulterior to the hypothesis with changes that may indicate an associated pathway which require further evidence for conclusions 5). Previous research designs on the application of meditation and epigenetics were conducted in shorter time frames in which there was a gap for a research study of meditation in a longitudinal design. This new research design prepares to address all of these gaps to provide additional experimental evidence within this topic.
Research Question
The research question asks: if trauma can be passed down to offspring through epigenetic changes, can psycho-spiritual interventions cause epigenetic changes that may reduce the potential to pass on transgenerational trauma responses?
Research Design
The proposed research study will be a longitudinal study with adult participants who have been diagnosed with PTSD and who have a history of adverse childhood experiences (ACEs). Research shows that health enhancing epigenetic changes were most strongly associated with long term meditators of 3 years or more. The current study will begin with 120 participants who fit the inclusion criteria and who are inexperienced meditators that agree to participate in a 1 year study. The study will require their participation in meditation 4x a week for at least 15 minutes a day. It is expected that some participants will drop out from the study. Participants will have access to a meditation app which will give guided meditations or timed meditations and will track their use & participation in the study.
Blood or saliva samples will be taken at baseline, at 6 months and at 12 months to analyze DNA profiles and detect epigenetic changes over time. DNA methylation, acetylation and deacetylation changes will be recorded to determine if long term meditation has an effect on epigenetic processes in people with PTSD and a history of ACEs who are new to the meditation practice. All blood samples will be analyzed and compared for epigenetic markers and changes which will build upon the foundations of previous research in the field.
Issues of Ethics
Participants will be given full consent of the study with written participation agreements. Participants will be excluded if they are currently suicidal or become suicidal during the study, meet DSM-V criteria for substance abuse, and are/were unable to refrain from additional therapy modalities (Bishop et al., 2018). If at any time someone in the study requires additional therapy or inpatient treatment they will be referred to the appropriate professionals and supported in leaving the study. All participants will be informed of the research results of the study. Confounding variables may be difficult to account for in a longitudinal study such as this. Participants will be selected based on similar demographics and their basic needs being met. The study will be presented to an appropriate review board prior to beginning and following all recommendations from that board.
Ethics informed
By studying previous research designs and observing the ethical standards that are required in psychological research, it was discovered that epigenetics research in humans with trauma had to be completed with participants who had naturally occurring adverse experiences. It was also found that extraction of DNA samples were obtained through saliva, blood samples, placenta, buccal epithelial cells, and cord blood (Berretta, Guida, Forni & Provenzi, 2021). Other studies that involved the application of stressful stimuli were only conducted on animals in order to follow ethical standards for psychological research.
Conclusion
In conclusion, it was found that trauma can be passed down to offspring through epigenetic changes, however, due to the germ cell reset period, some trauma responses were inherited through the environment as secondary epigenetic changes. There was evidence to support changes and reduction of trauma stress responses from psycho spiritual growth interventions such as meditation. These results are not thoroughly conclusive in resolving trauma responses, but do show promising results in long term meditators.
The results from this literature review give evidence to show that epigenetic changes can occur from mind-body-spirit interventions. This is an important recognition for psychology professionals as many therapeutic interventions incorporate mindfulness practices into treatment models. The results of this research review gives psychology professionals and spiritual development advocates promising foundations to support that trauma responses can be reversed through psycho-spiritual interventions.
References
Berretta, E., Guida, E., Forni, D., & Provenzi, L. (2021). Glucocorticoid receptor gene (NR3C1) methylation during the first thousand days: Environmental exposures and developmental outcomes. Neuroscience and Biobehavioral Reviews, 125, 493–502. https://doi-org.ezproxy.snhu.edu/10.1016/j.neubiorev.2021.03.003
Bishop, J. R., Lee, A. M., Mills, L. J., Thuras, P. D., Eum, S., Clancy, D., Erbes, C. R., Polusny, M. A., Lamberty, G. J., & Lim, K. O. (2018). Methylation of FKBP5 and SLC6A4 in Relation to Treatment Response to Mindfulness Based Stress Reduction for Posttraumatic Stress Disorder. FRONTIERS IN PSYCHIATRY, 9. https://doi-org.ezproxy.snhu.edu/10.3389/fpsyt.2018.00418
Kaliman, P. (2019). Epigenetics and meditation. Current Opinion in Psychology, 28, 76–80. https://doi-org.ezproxy.snhu.edu/10.1016/j.copsyc.2018.11.010
Kaliman, P., Álvarez-López, M. J., Cosín-Tomás, M., Rosenkranz, M. A., Lutz, A., & Davidson, R. J. (2014). Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators. Psychoneuroendocrinology, 40, 96–107. https://doi-org.ezproxy.snhu.edu/10.1016/j.psyneuen.2013.11.004
Krippner, S., & Barrett, D. (2019). Transgenerational trauma: The role of epigenetics. Journal of Mind and Behavior, 40(1), 53–62.
Lucero, I. (2018). Written in the body?: Healing the epigenetic molecular wounds of complex trauma through empathy and kindness. Journal of Child & Adolescent Trauma, 11(4), 443–455. https://doi-org.ezproxy.snhu.edu/10.1007/s40653-018-0205-0
Ramo-Fernandez, L., Schneider, A., Wilker, S., & Kolassa, I.-T. (2015). Epigenetic Alterations Associated with War Trauma and Childhood Maltreatment. Behavioral Sciences & the Law, 33(5), 701–722.
Venditti, S., Verdone, L., Reale, A., Vetriani, V., Caserta, M., & Zampieri, M. (2020). Molecules of Silence: Effects of Meditation on Gene Expression and Epigenetics. FRONTIERS IN PSYCHOLOGY, 11. https://doi-org.ezproxy.snhu.edu/10.3389/fpsyg.2020.01767