Adverse Childhood Experiences: A Metabolic View
Ever since I was little, Christmas has always been one of my favorite holidays! When December rolls around, no matter what else was going on in our lives, my mom and I always take the time to destress and bake some seriously delicious gingerbread cookies.
Baking, like most things, is a process; first you read the recipe and find what ingredients are needed for the food you are trying to create. Then, you have to prepare the ingredients! Mixing flour and water together to form your dough, and then breaking it apart into smaller chunks so that you have a bunch of cookies to eat. It’s an art that requires multiple steps and processes; after we finish decorating our cookies we put them in the oven to heat up and get nice and warm, solidifying into the gingerbread men we all know and love.
Once our cookies finish baking, we usually invite our family to gather around the kitchen table trying them. I knew the taste and texture of each bite was delicious, but what I didn’t know, was that with every chew and swallow, 37 TRILLION different chemical reactions were taking place inside of my body at any given moment. And these reactions were actually quite similar to the process I used in baking my gingerbread cookies!
Metabolomics: What on earth is it?!
This process is called metabolomics. Metabolomics is the study of every single chemical reaction that takes place within an organism, and the human metabolome is the collection of the metabolites, the chemical components used used and produced in each and every chemical reaction! When we know about the metabolites in our body, we can learn about so many different things, from the way chocolate affects human alertness, to the way adverse childhood experiences affect adult development and even onset diseases.
We look at metabolomics much like we would baking or cooking any other Christmas treat! First, we need to figure out what metabolites are going to be used in different chemical reactions, just like we would need to look at the ingredients for baking cookies; for this, we use a mass spectrometer to send energy out to cells and see what energy is sent back, producing a graph like this that can actually tell us exactly what metabolites are present in our body, and what their concentrations are
Next, these metabolites are broken down or built back up, much like how we made our dough and separated it. Metabolites are involved in two major chemical processes; catabolism and anabolism; in catabolism, larger compounds are broken up into smaller ones to produce energy. Anabolism is the opposite of this process; it is when small compounds come together and react to form larger ones, subsequently producing energy.
Finally, metabolomics also requires multiple processes for different reactions to occur; unlike baking, it is much more complicated than just putting some cookies in an oven and having them ready to eat right away. One chemical reaction can cause millions of other reactions to occur within the body. It is just like a domino effect!
With a domino effect, one event causes numerous others to occur, and this is how metabolic dysfunction caused by adverse childhood experiences can have such an extreme impact on childhood neurodevelopment, and even future risk of adult-onset diseases.
ACEs: Adverse Childhood Experiences
The term “Adverse childhood experiences” covers 10 ACE’s that can be divided into three categories; abuse, neglect, and other household traumas. ACE’s influence health by disrupting the neurochemistry of the body through a prolonged, chronic stress response. This leads to things such as cognitive impairment, the adoption of health risk behaviors, disease and disability, and even early death!
The body adapts to stressful situations by activating neural mechanisms that release stress hormones like adrenaline in what we commonly call the “fight or flight response”. These stress hormones are called catecholamines, and if they are upregulated, they can wreak havoc on the body.
The HPA axis is what is in charge of this response, and it is named for its three essential parts; the hypothalamus, the pituitary gland, and the adrenal gland. All three provide separate but intertwined functions responsible for the stress response. First, the hypothalamus in the brain releases hormones that stimulate the pituitary gland, finally causing the adrenal release of catecholamines, followed by the release of cortisol.
At a certain blood concentration of cortisol, the body decides that the threat has been properly dealt with and the cortisol exerts negative feedback to stop the stress response. At this point, the body returns to its normal healthy state. This is not the case over long periods of time though.
With repeated exposure to stressors, humans begin to produce more and more catecholamines every time the stress response is triggered, and this can fundamentally change one’s brain chemistry and even their DNA. With chronic hormone release, also comes chronic inflammation, leading to serious risks of heart failure, diabetes, obesity, and depression as these children grow up. On average people with 6 or more ACES die 20 years earlier than those with none.
Catecholamine Biosynthesis
Using PathWhiz, an online biological pathway diagramming platform, I was able to study the Catecholamine Biosynthesis pathway depicts the synthesis of catecholamine neurotransmitters. Catecholamines are chemical hormones released from the adrenal glands in the kidney as a response to stress that activates the sympathetic nervous system in the brain.
Catecholamines include epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine. Cortisol is not actually a catecholamine; it is a stress hormone produced after the release of epinephrine, after the hormones have traveled from the adrenal medulla in the kidney, through the bloodstream and back to the brain when the sympathetic nervous system is activated.
Feel free to skip this part if big science words and chemical reactions aren’t your thing. It’s about to get real complicated…
Catecholamines are synthesized in the adrenal gland in your kidney by four enzymes. The first is tyrosine hydroxylase. When tyrosine, oxygen, and Sapropterin react together, it produces L Dopa, BH2 and water. L Dopa is very important because it is the immediate precursor to dopamine production.
The L-DOPA is then converted into dopamine and carbon dioxide via the AADC enzyme.
The dopamine then reacts with oxygen and ascorbic acid to become norepinephrine via the dopamine beta-hydroxylase enzyme. This reaction additionally produces water and dehydroascorbic acid.
Norepinephrine is finally converted to epinephrine, AKA adrenaline, via the PNMT enzyme.
The epinephrine then travels through your bloodstream, constricting your muscles and increasing your heart rate, before finally reaching your brain. Cortisol follows the epinephrine, and at a certain blood concentration of cortisol, the body decides that the threat has been properly dealt with and the cortisol exerts negative feedback to stop the stress response. At this point, the body returns to its normal healthy state. This is not the case over long periods of time though.
Now, that process is really complex, and I replicated each and every step from a pre-existing PathWhiz diagram so that I would have the background knowledge for the bigger project I am working on. I am trying to map all of the chemical reactions that occur within the HPA axis and stress response system, not just catecholamine biosynthesis. Below is a very rough depiction of what I have so far:
ACE’s are very important to me, and understanding them may play a giant role in healthcare as we move forward into this next decade, and even this century. ACE’s and the consequences of an up-regulated stress response do not only affect adults; the genetic changes associated with ACE’s can be passed down to one’s children, increasing their risk for disease as well!
Fortunately, scientists are already looking at ways we can treat and reverse the consequences of ACE’s. They are working to treat the underworking biological processes, not just the symptoms and diseases that arise out of a dysfunctional stress response. Regular exercise, healthy eating habits, and normal sleep patterns can help to decrease can reduce your stress response, and therefore your risk of developing diseases.
At the same time, this doesn’t mean we are going to give up eating cookies! Actually, by working to stay calm and attain happiness in life, you may decrease your stress hormones even further, so take a break, bake a cookie, and enjoy the holidays, because you just may be adding years onto your life!
Make sure to leave a clap on this article and email me at faithinello@gmail.com to ask questions about my work in metabolic pathway analysis, talk to me about my chemical relationships, or chat more about adverse childhood experiences and why it is so important to better understand them!
