Scarred For Life: The Epigenetics of Fear

When someone is truly scared or traumatized, they might say they were “scarred for life”. While this might seem like a metaphor, recent studies show that fear might actually leave permanent epigenetic marks on your DNA, marks you could potentially pass down to your children or grandchildren.

Fear is a basic biological process. In their lifetime everyone has experienced it in one form or another, and we are all afraid of different things.  From fear of physical things like spiders, snakes or clowns to fear the intangible like fear of intimacy and failure. Diseases such as anxiety and Post Traumatic Stress Disorder (PTSD) are associated with heightened fear responses.  Fear can shape our lives and has a very powerful hold over our psyche, but why do we fear things, even irrationally? Is it based solely on an individual’s own experiences or could fear be an inherited trait?

Nature or Nurture

Sometimes fear is learned.  At one point in our lives, we may come across something that conditions us to be afraid either rationally or irrationally.  For example, a child who comes into contact with a hive of angry bees might be afraid of bees well into adulthood.

Fear produces a stress response which is the result of reactions occurring in the area of the brain involved with “fight or flight” including the hypothalamus and the amygdala. 5 Depending on the severity of the response, brain functioning may be altered resulting in abnormal behavior responses.  The associated fear memory can be acute or prolonged causing anxiety, depression, and even PTSD. Many of these disorders have been found to be associated with various epigenetic mechanisms.

In an article published in Learning and Memory, the authors state, “Stress elicits both immediate and long-lasting psychological, physical, and emotional strain on an individual, leading to profound neurobiological changes that impact future behavioral responses. Animal models of stress exposure have identified epigenetic modifications in key brain areas known to be critical components of the circuitry responsible for both the expression of anxiety and formation and expression of fear memories, such as the frontal cortex, hippocampus, and amygdala” 1

Although it is sometimes damaging, fear is a biological necessity for survival. A mouse that is not afraid of a cat might not last as long as the mouse that is. But why is a mouse who has never seen a cat afraid of it? If fear is solely a learned response the mouse should show no fear towards a cat, but that is not always the case. It is understood that fear responses are naturally hardwired into the brains of certain species making them a necessary evolutionary trait.  To better understand the mechanisms of fear, scientists are focusing their attention on the field of epigenetics.

Epigenetics is the study of gene expression that does not involve changes to the underlying DNA sequence. Every cell in the body contains the same set of genes, but marks made on genes turn on and off particular genes that dictate cell function. Many of these epigenetic marks are believed to be heavily influenced by environmental factors such as diet and stress and may be responsible for everything from cancer to obesity, as well as numerous psychological disorders.

Studying the Epigenetics of Fear

Fear conditioning is used to study the emotional effects of stressors on a subject. Generally, a subject is exposed to something benign, like a picture of a flower while simultaneously being exposed to something unpleasant like being doused in ice cold water. Eventually, the subject learns to associate the benign picture of a flower with being doused in water. The aversion stays through even when the subject is exposed to just the flower and not the water. Unlocking the biological process of how fears develop and how they affect us physically may help future generations with panic disorders, anxiety, and PTSD.

Some studies suggest that the epigenetic changes fear can produce might be so impactful it can be passed down through generations.

In a study performed at Emory University in 2014, researchers used fear conditioning to study the impact it had on future generations. The study trained male mice to fear a particular scent called acetophenone by exposing them to the smell before introducing small electric shocks. The animals soon learned to associate the smell with pain and exhibited fear responses even without the electroshock.   This reaction was passed down to the mice’s children and even their grandchildren despite those generations never being exposed to the electroshock.  The researchers claim low DNA Methylation levels on the genes responsible for sensing the odor is too blame.(2,3)

DNA methylation occurs when a methyl group attaches to a cytosine base on the DNA strand. It is believed that there is a relationship between DNA methylation and gene expression. Highly methylated DNA is associated with a gene being suppressed.

How we react to stress is also a factor to how we develop fear.  Certain epigenetic factors either inherited from our parents or experiences early in life can make a person more or less susceptible to stress and fear.  In one experiment mice were removed from their mother’s early on, recreating what would be a major childhood trauma in humans. Those mice were found to have heightened fear and anxiety as adults as well as altered DNA methylation patterns on stress-response genes such as CB1 and CRF2 in the cortex. These traits were also passed down to the next two generations of offspring despite the fact their offspring were never separated from their mothers.  (6,7)

In other studies, male mice exposed to extreme stress had their offspring experience heightened fear response and increased stress hormone levels despite never experiencing the stressful environment their fathers and grandfathers had endured.

These are not the only studies to look at how epigenetic damage occurred during trauma affecting future generations.  The Holocaust was one of the most tragic and traumatic events in human history.  Survivors faced a lifetime of complications including having lower levels of cortisol, a hormone that helps the body return to normal after trauma.  They also had lower levels of a particular enzyme that breaks down cortisol, probably to make sure the body didn’t break down what little they had. The children of survivors were also found to have lower cortisol levels, but higher levels of the enzyme that breaks it down.

According to an article in Scientific American “The enzyme is usually present in high levels in the placenta to protect the fetus from the mother’s circulating cortisol. If pregnant survivors had low levels of the enzyme in the placenta, a greater amount of cortisol could make its way to the fetus, which would then develop high levels of the enzyme to protect itself.”4

Because of this, it is thought that children of Holocaust survivors have a higher sensitivity to stress.

When Fear Goes Wrong

Normally a traumatic event becomes nothing more than a bad memory. We may have negative reactions when exposed to the things we learn to fear, but if we are exposed to those stressors without a negative impact enough, that fear dissipates in a process called extinction. For example, if the child who was afraid of bees was around bees multiple times without being stung he might lose his fear. This is why exposure therapy is popular for people with phobias.

Sometimes the brain does not process those memories correctly.  When that occurs, panic disorders, anxiety, and PTSD can develop. The National Institute of Mental Health describes PTSD as:

“a disorder that develops in some people who have experienced a shocking, scary, or dangerous event. It is natural to feel afraid during and after a traumatic situation. Fear triggers many split-second changes in the body to help defend against danger or to avoid it. This “fight-or-flight” response is a typical reaction meant to protect a person from harm. Nearly everyone will experience a range of reactions after trauma, yet most people recover from initial symptoms naturally. Those who continue to experience problems may be diagnosed with PTSD. People who have PTSD may feel stressed or frightened even when they are not in danger.”

People with PTSD experience symptoms such as anxiety, flashbacks and can develop depression and symptoms can be debilitating. An estimated 5% or 13 Million people suffer from some form of this disorder in their lifetime.

Some studies have found that epigenetic factors such as DNA methylation are present in those diagnosed with PTSD. One study in particular found that reduced methylation of the glucocorticoid receptor (NR3C1-1F) region in the peripheral blood of veterans with PTSD compared to veterans without PTSD. This region is thought to be important for regulation of stress.

Not everybody who experiences fear or trauma develops PTSD.  Researchers are looking into how fear and memory play a part in the development of this disorder and are trying to figure out if epigenetics holds a potential for treating PTSD, anxiety and panic disorders.

  1. Blouin AM, Sillivan SE, Joseph NF, and Miller CA. The potential of epigenetics in stress-enhanced fear learning models of PTSD, Learning & Memory, vol. 23(10):576-86 (2016)
  2. Dias BG, Ressler KJ. Parental olfactory experience influences behavior and neural structure in subsequent generations, Nature Neuroscience vol, 17: 89–96 (2014)
  3. Callaway E. Fearful memories haunt mouse descendants, Nature, 1 Dec 2013
  4. Rodriguez T. Descendants of Holocaust Survivors Have Altered Stress Hormones, Scientific American, 1 March 2015
  5. What Part of the Brain Controls Emotions?. Healthline , 2018.
  6. Franklin TB, Russig H, Weiss IC, Gräff J, Linder N, Michalon A, Vizi S, Mansuy IM. Epigenetic transmission of the impact of early stress across generations, Biological Psychiatry, vol.68(5):408-15 (2010)
  7. Yeshurun S, Hannan AJ.Transgenerational epigenetic influences of paternal environmental exposures on brain function and predisposition to psychiatric disorders, Molecular Psychiatry, March 2018

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