The Impacts of Epigenetics on Health, Behavior and Your Brain
Do you have epigenetic envy? I do at times. Do you know what epigenetics even is? Let me explain.
In simple terms, epigenetics refers to how different chemical and physical modifications can impact DNA function. That’s right, our environment and lifestyle choices actually modulate how our genes express themselves! For my fellow geeks out there, here’s a really scientific explanation which discusses the mechanisms behind these modifications (bold emphasis mine):1
Epigenetics refer to the study of the epigenome, chemical and physical modifications taking place in the DNA molecule, and altering the capacity of a gene to produce more or less of its coded mRNA. Given the high complexity of DNA organization, these modifications are expected to follow a defined pattern allowing the underlying molecular mechanisms to be performed correctly and to decode DNA in the context of chromatin. Epigenetic mechanisms refer to DNA methylation , histone modifications , and, more recently, posttranscriptional mechanisms such as microRNA [42,43]. Generally, DNA methylation has been suggested to direct transcriptional repression . However, recent evidence suggest that this may be particularly true for methylation found within gene’s promoter while intra- and inter-genic methylation may be associated with the use of alternative promoters and active transcription . At the chromatin level, high histone acetylation and low histone methylation levels have been associated with active transcription . This being said and as mentioned previously, epigenetic mechanisms are thought to be involved in the modification of gene expression induced by environmental factors. As such, it is possible to conceptualize the epigenome as an interface on which environment can act to influence normal genetic processes and to hypothesize that epigenetic mechanisms may account, at least in part, for the regulation of behavior as a response to environmental adversity.
These next few months are getting a little hectic for me as I prep for my functional medicine certification, BreakFree Medicine book release, website redesign, and a few other projects and events. It’s definitely an exciting and potentially stressful time. What does this have to do with epigenetics? Well, how my body responds isn’t just related to my temperament or my genes, but epigenetic modifications that occurred throughout my life, even prenatally. Let me explain.
A Walk Down Human Genome Lane
In 2003, the Human Genome Project (HGP) identified that humans contain approximately 20,500 genes, much less than the original estimates. It was thought that, with this mapping out of our “book of life,” major advances in disease causes and their treatments would ensue. According to the National Human Genome Project website:
Upon publication of the majority of the genome in February 2001, Francis Collins, the director of NHGRI, noted that the genome could be thought of in terms of a book with multiple uses: “It’s a history book – a narrative of the journey of our species through time. It’s a shop manual, with an incredibly detailed blueprint for building every human cell. And it’s a transformative textbook of medicine, with insights that will give health care providers immense new powers to treat, prevent and cure disease.”2
However, as time progressed, it became apparent that having knowledge of our human genetic blueprint wouldn’t provide the answers to our health problems. This was especially made evident when the Human Microbiome Project discovered all the tiny microbes that inhabit our insides outnumber our cells ten to one. These little bugs interact with our biochemistry and have a profound impact on our health. According to the article, “The Human Microbiome: Our Second Genome-”3
The human microbiome is a source of genetic diversity, a modifier of disease, an essential component of immunity, and a functional entity that influences metabolism and modulates drug interactions.
As time progresses it is becoming clearer that our lifestyle choices, single nucleotide polymorphisms (which are variances in genes verses mutations, called SNPs), the health of our microbiome, along with environmental cues were the missing pieces in determining if a genetic predisposition became our health destiny. In fact, even those with chromosomal mutations may benefit their health from changes in diet, lifestyle, and modulating certain SNPs.3-6
(Epigenetic) Stress on the Brain
Therefore, it’s actually a powerful discovery that how we treat our gut bugs and the lifestyle we choose can modulate our health outcomes by interacting with our genes. We are not victims of our DNA. Furthermore, we can use this information to empower us to take certain actions or understand our behavioral tendencies.
For example, several studies have shown that mamma’s stress prenatally and adverse childhood events can cause “epigenetic biomarkers” in the brain, modulating behavioral responses and risk for emotional disorders.7-9 One study in 2011 reports (bold emphasis mine):7
Ultimately, the identification of “epigenetic biomarkers” in distinct genomic regions may provide important information for the understanding of biological processes underlying mental diseases and thus allow for the development and design of new therapeutics. Though expression and DNA methylation changes in the brain are more obviously relevant to changes in behavior, comparable changes in blood might provide a clinically valuable surrogate, given the easy access to this tissue in patients. Some early studies have shown partial correlations in gene expression between various brain regions and blood (e.g., Brown et al., 2001), which have been supported by following data demonstrating epigenetic differences in lymphocytes associating with the brain in Rett syndrome and Alzheimer’s disease (e.g., Wang et al., 2008). Recently it was described that chronic corticosterone exposure in mice stimulated parallel increases in FKBP5 expression between brain tissues and blood together with some, generally subtle, alterations in DNA methylation at the promoter of this gene (Lee et al., 2010). However, the other candidate HPA axis genes tested in this study – namely, NR3C1, HSP90, CRH, and CRHR1 – failed to show such effects while further studies in this area of research also describe little correlation (e.g., Yuferov et al., 2011). Consequently, the prospect of diagnostic epigenetic testing for mental diseases using markers in the blood appears so far unresolved, and certainly further research is required.
The article further discusses that timing of these stressors can impact which region of the brain is effected:
Developing brain regions typically pass through critical “windows” of sensitivity that stretch over different perinatal periods. Therefore, it stands to reason that the impact of stressors at different time-points will confer more pronounced and long-lasting effects within brain regions that are actively developing at that particular time.7
In fact, these effects can impact our genes in more than just the brain. According to the National Institute of Health (bold emphasis mine): 9
New research, published in the May 14, 2013, issue of the Proceedings for the National Academy of Sciences, shows that PTSD patients who were abused as children have different patterns of DNA methylation and gene expression compared to those who were not…
To focus on the effect of childhood abuse in PTSD, the researchers examined genetic changes in peripheral blood cells from PTSD patients with and without previous exposure to childhood maltreatment. These were then compared to the trauma-exposed group that did not develop PTSD to rule out changes associated with trauma exposure alone.
Despite sharing a few common biological pathways, 98 percent of the changes in gene expression patterns in PTSD patients with childhood abuse did not overlap with those found in PTSD patients without childhood abuse. Interestingly, PTSD patients who experienced significant abuse as children exhibited more changes in genes associated with central nervous system development and immune system regulation, whereas those without a history of childhood abuse displayed more changes in genes associated with cell death and growth rate regulation.
Therefore, what happens prenatally and in childhood may be the reason why you can remain cool as a cucumber or, alternatively, reflexively respond to triggers. Interestingly, these responses also alter biochemical pathways resulting in different health outcomes for the individual.
In my Saratoga.com blog, I discuss some recent examples of epigenetics and health outcomes, from Fido to Buggy interactions.
- Labonté B, Turecki G. Epigenetic Effects of Childhood Adversity in the Brain and Suicide Risk. In: Dwivedi Y, editor. The Neurobiological Basis of Suicide. Boca Raton (FL): CRC Press/Taylor & Francis; 2012. Chapter 13. Available from: http://www.ncbi.nlm.nih.gov/books/NBK107193/
- National Human Genome Project. An Overview of the Human Genome Project. NIH. June 29, 2015. http://www.genome.gov/12011238
- 3. Grice EA, Segre JA. The Human Microbiome: Our Second Genome. Annual review of genomics and human genetics. 2012;13:151-170. doi:10.1146/annurev-genom-090711-163814.
- National Human Genome Project. Frequently Asked Questions About Genetic Disorders. What are genetic disorders? NIH. November 10, 2015. http://www.genome.gov/19016930
- Hyman M. Chapter 26: Clinical Approaches to Environmental Impacts. Textbook of Functional Medicine. Available at: https://www.functionalmedicine.org/content_management/files/FunctionalNutritionProgramDec2010/4_Foundational%20Webinars%20and%20Reading%20Material/Textbook%20of%20Functional%20Medicine%20Chapters/Chapter%2026.pdf
- Schwarz, F. Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline. PNAS. November 30, 2015. doi: 10.1073/pnas.1517951112
- Murgatroyd C, Spengler D. Epigenetics of Early Child Development. Frontiers in Psychiatry. 2011;2:16. doi:10.3389/fpsyt.2011.00016.
- Mehta D, Klengel T, Conneely KN, et al. Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(20):8302-8307. doi:10.1073/pnas.1217750110.
- Zhao R. Child abuse leaves epigenetic marks. NIH: Genome Advance of the Month. https://www.genome.gov/27554258