Lizzy Stevens ’16, Lisa Wiesenberger ’16, and Ejonia Korcari ’16

            “I even felt lonely when mum and dad were in the house, because mentally they were completely out of it” Sophie shared with the National Society for the Prevention of Cruelty to Children. “Backing me into a corner until I was whimpering and crying, he would just laugh at me and walk away, satisfied by my distress” is a piece of Fiona’s story.

There is an exposure in our society that is increasing the risk of suffering from seven out of the ten leading causes of death but can not be prevented by eating healthy and exercising daily2. It is an exposure that doctors are not routinely trained to screen for and treat although it casts a long shadow upon the lives of individuals. It affects the development of the brain, the stress response system, hormonal regulation, and even our DNA6. This exposure is early life adversity, namely childhood abuse.

This essay will be discussing how childhood environments, such as abusive homes, can influence a person’s biology and their risk for depression and suicide later in life. The last essay stated how maternal care affects the animals, and now how care affects humans will be described. To begin, what is childhood abuse and what effect can it have upon a child?

When we talk of abuse, we often immediately think of physical abuse, but there are other forms as well such as constant family conflict, harsh discipline and emotional neglect6. Clinical studies are showing that these various forms of child abuse can influence kids in a harmful way – by affecting the genes and DNA of the brain within a child6. Other studies are showing that child abuse can lead to an increased risk of developing anxiety and mood disorders, such as depression. According to the World Health Organization, major depressive disorder is the most common mood disorder, affecting approximately five percent of the world’s population so it is important that we investigate the potential influence of child abuse upon the brain. The first question to ask is, how does childhood abuse, which involves social interaction and behavior between parent and child, affect the development of the brain at the level of DNA?

Epigenetics is the regulation of genes and how these genes are expressed. But, first, we must understand the question, what is DNA and what is a gene?

Each cell of an organism contains identical DNA. DNA is like a book or instruction manual for cells; it is the sequence of information that contains the directions for every single cell of the body. These directions are organized into specific segments called genes, kind of like the chapters of a book. It would seem that all the cells in our body are the same since they all contain this same DNA and set of instructions; however, this is not the case. Our body has many different forms of cells such as liver cells, heart cells, and muscle cells. What differentiates, for instance, a liver cell from a heart cell is which part of the DNA book is read, which is determined by which chapters are tagged shut or open. These tags are added to or removed from the cells during development or during different life experiences; this is epigenetics and the tags that increase or decrease reading are called epigenetic modifications.

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For example, a liver cell has all of the book chapters for every single cell in the body, however, only the

chapters needed to make liver cell are open and read. Meanwhile the chapters that give instructions for the heart cell or the muscle cell are tagged shut and are thus not read in the liver cell.

The epigenetic tag that we will be discussing is called a DNA methyl group which is added to a subunit of DNA to open or close different chapters of the DNA book. When this tag is added, it sits on the DNA in such a way that the processing is reduced.

Let’s take a step back for a moment to make sense of this.

There is processing machinery in our body that will read the chapters of the DNA book to make a product from the instructions. Often, the product that is made is a protein, which is a molecule in our bodies that carries out some sort of important task. Imagine that you have the instruction manual for a chair that you just bought at Ikea. You are the machinery that will build this chair. You must read the instructions to then build the product, the chair, that serves an important function which is to hold someone who is sitting down. Now, if some chapters of your instruction manual have tags closing them shut, then you won’t be able to read the directions and properly make your product. This same idea is going on here. In Figure 1, the gene on the bottom has methyl tags attached which keeps the gene from being read and keeps the protein product from being made.

Additionally, a requirement of epigenetics is that the modifications, or tags, are heritable and can be passed down from mother to child to grandchild. For example, how a mother treats her children will change the tags that are on the children’s genes in their brain cells. This can cause changes in the behavior of the children that can ultimately lead them to act differently towards their own children. The key idea is that the environment, in this case child care, can change the way our genes are tagged and read. This concept started taking flight when an animal study showed that the care that a mother rat exhibits towards her pups during childhood affects the pups’ ability to handle stress later in life10. This study led scientists to question whether this same thing happens in humans; does child care shape the child’s ability to handle stress? If so, then parental care in the early life of humans can have an extremely important impact upon mental health, specifically the likelihood of suicide and depression in individuals.

A human study published in 2009 investigated whether individuals who experienced childhood abuse showed changes in the expression of their stress genes5. The scientists specifically looked at the presence of the stress hormone receptor in a particular region of the brain. First, what is a hormone and what is a receptor?

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A hormone is a chemical messenger that sends information to different parts of the body. A receptor is what receives the information from the hormone and picks up the signal to tell the cell how to respond.

Imagine that a hormone is a general’s command in an army- it sends out the information to everyone. The receptors are like the soldiers- they receive the instructions and carry out the tasks.

Figure 2 shows how this works. The hormone travels to the receptor, attaches to it, then launches some sort of action in the cell. In this case, we are talking about a stress hormone that activates a receptor called the glucocorticoid receptor that controls how and how long a person responds to stress. In fact, it helps people (and animals) respond to a stressful event fast and then to go back to normal.

What does this have to do with genes and tagging DNA? Why are we talking about this hormone receptor and the response it causes?

It is the tagging of this stress hormone receptor gene that can be changed by childhood abuse. In other words, this gene is one chapter of the DNA book that contains the instruction to make this stress hormone receptor. Individuals who experience childhood abuse, however, can actually have an increased number of tags on this gene, meaning that this chapter is barely open and the machinery can’t read what it says5. In turn this means that there are fewer stress receptors and so now the effect of the stressful event lingers in the body rather than going away fast and returning to normal. How exactly, though, did the scientists figure this out?

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To investigate what was happening in the brains of people who have experienced child abuse, researchers looked at the hippocampal tissue of individuals after death. The hippocampus is a region of the brain that has these stress hormone receptors and is involved in learning and memory. They looked at the presence of the stress hormone receptor in suicide victims with a history of childhood abuse and compared this to the presence of stress hormone receptor in suicide victims that do not have a history of child abuse5. Specifically, they looked at the DNA methyl tags that were added to this gene; remember this is how the DNA chapter is shut close.

And the researchers found something interesting as illustrated in Figure 3. The bottom image shows the gene of an abused suicide victim. There are increased methyl tags sitting on the DNA, which leads to less receptors in the brain. The next question to ask is, what does this have to do with our ability to handle stress and what effect does this have upon depression and suicide?

The fewer stress receptors that are present, the less robust the stress response is. In other words, the people who experienced child abuse had more DNA methyl tags, fewer stress hormone receptors, and were thus less able to cope with stress because the stress response lingers instead of going away fast5. It’s as if a general shouts a command, but few soldiers are there to hear the message, so there is less of a response to the action that the general is demanding.

Unfortunately this reduced ability to cope with stress may sometimes lead to depression and suicide. In this study, the researchers concluded that the people who faced childhood abuse and didn’t have nurturing interactions with their parents, had fewer stress response receptors in their brain5. Thus they were more affected by stress and this may possibly have led to their suicides. It is extremely important at this point, however, that we note that child abuse doesn’t necessarily result in suicide or depression, nor does one or more of those conditions mean that a person was abused as a child.

This is all relevant to today’s society in thinking about how individuals parent their children and the environments in which kids are raised. It is interesting to note that, for the brain, parental neglect is as bad as abuse. While poor environments can negatively impact stress coping abilities, it should also be noted that positive parental relationships can actually serve as a source of resilience to chronic stress and can reduce the vulnerability to mental illness in a child8. This shows how crucial it is that we acknowledge how important the parent to child relationship is during early life.

Sometimes science, such as the talk of genes, can seem hard to connect to our own lives, but today we told you that what we do and how we interact with one another has very real and important consequences on the science of our bodies. There is a common debate of “nature” versus “nurture,” which asks whether the genes that we are born with, or the environment and social interactions that we grow up with, have a greater impact upon who we become. Neuroepigenetics brings these two ideas together and demonstrates how they are not exclusive – our behavior towards our children, specifically the abusive behavior of some parents, can change their genes and thus change their behavior.

To combat some of these negative effects, we as a society should educate parents on this topic. During pregnancy, parents are given abundant information about how to best care for their fetus, but this information trade is typically reduced after birth. While parenting books do exist, it is vital that we implement programs to teach parents about these behavior-to-gene interactions in order to give children the best environment possible for growth.

In conclusion, child abuse and neglect leave harmful imprints upon the stress coping abilities of a child. Unfortunately this can sometimes lead to depression or suicide. On a fortunate note, however, many local resources are available in numerous communities and on the internet. To report instances of child abuse or to find help, google your local and state child protective services, or contact the National Child Abuse Hotline 1-800-4-A-CHILD. If there are any questions regarding the topics discussed in this essay, please email us at theneuroepicpodcast@umich.edu.

References

  1. Egeland, Byron. Jacobvitz, Deborah. Sroufe, Alan L. (August 1988). Breaking the Cycle of Abuse. Child Development 59, 1080-1088. http://www.jstor.org/stable/1130274?seq=1#page_scan_tab_contents
  1. Harris, N. (2014, September). How childhood trauma affects health across a lifetime. https://www.ted.com/talks/nadine_burke_harris_how_childhood_trauma_affects_health_across_a_lifetime/transcript?language=en
  2. Heim, Christine. Nemeroff Charles B.(15 June 2001). The Role of Childhood Trauma in the Neurobiology of Mood and Anxiety Disorders: Preclinical and Clinical Studies. Biological Psychiatry 49, 1023–1039 http://www.sciencedirect.com/science/article/pii/S000632230101157X
  3. Johannes Gräff, Dohoon Kim, Matthew M. Dobbin, Li-Huei Tsai. Physiological Reviews. Published (1 April 2011) Vol. 91 no. 2, 603-649. http://physrev.physiology.org/content/91/2/603
  1. McGowan at al. (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse Nature Neuroscience. 12(3):342-8. http://www.ncbi.nlm.nih.gov/pubmed/19234457
  2. Meaney, M. J. (2001). Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annual Review of Neuroscience, 24, 1161-92. http://proxy.lib.umich.edu/login?url=http://search.proquest.com/docview/198862441?accountid=14667
  3. Rutter M. (1979). Protective factors in children’s responses to stress and disadvantage. Prim. Prev. PsychopathoL 3:49-74. http://www.ncbi.nlm.nih.gov/pubmed/547874
  4. Smith J, Prior M. (1995). Temperament and stress resilience in school-age children: a within families study. J. Am. Acad. Child Adolesc. Psychiatry 34:168-79 http://www.sciencedirect.com/science/article/pii/S0890856709637552
  5. U.S. Department of Health and Human Services: Administration for Children & Families. Child Maltreatment (2013). http://www.acf.hhs.gov/programs/cb/resource/child-maltreatment-2013
  6. Weaver at al.(2004) Epigenetic programming by maternal behavior. Nature Neuroscience 7, 847 – 854. http://www.nature.com/neuro/journal/v7/n8/abs/nn1276.htm

Image Sources

Figure 1: http://www.epibeat.com/what-is-epigenetics/

Figure 2: http://www.ks.uiuc.edu/Research/methylation/

Figure 3: http://www.endocrinesurgeon.co.uk/index.php/what-are-intracellular-receptors

Featured Image Source

Mother hug her little daughter Love stock vector (royalty free) 1606953517. Shutterstock. (n.d.). Retrieved September 7, 2022, from https://www.shutterstock.com/image-vector/mother-hug-her-little-daughter-love-1606953517

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