Genetics & Neurotransmitters
Neurotransmitters are the chemical messengers our brains use to communicate. They regulate many states of mind including happiness, alertness, pleasure, sleepiness, reward and much more. While lifestyle, environmental exposures, and endogenous health conditions can all impact neurotransmitters, genetics can also play a role. For individuals with longstanding mental health conditions and family histories of mental health conditions, I evaluated genetic variants that could be impacting neurotransmitter levels and mental health.
Here’s how it works:
Genes code for proteins and those proteins have different jobs in our body. One class of proteins is enzymes. The job of enzymes is to speed up a biochemical reaction. When it comes to neurotransmitters and inflammation, enzymes can help make them or break them down. When you have a variant (variant is a change in its DNA sequence that can affect the function of the protein it codes for) in a gene, the protein it codes for may not work optimally. This can cause the biochemical pathway that protein runs to go either faster or slower, leading to too many or too little neurotransmitters, or too much inflammation. Changes in neurotransmitter levels and inflammation can both impact the brain. It is also important to understand that enzymes use nutrients to run, just like cars use gas. So, nutrient deficiencies can further worsen problems created by genetic variants. There are a few genetic pathways that I focus on when it comes to mental health:
Methylation
You may have heard of the MTHFR genetic variant. MTHFR is one of many enzymes in a process called the methylation cycle. The methylation cycle helps our body: make and break down neurotransmitters, synthesize DNA and intracellular energy, make nitric oxide, detoxify, and reduce inflammation. So, it's important. Variations in not just the MTHFR gene, but any of the genes involved in the methylation pathway, can lead to impacts on mood. Here are some of the main ways the methylation pathway impacts mood:
The methylation pathway makes a compound called SAM-e that helps our brains eliminate stress neurotransmitters. Studies have shown that SAM-e can help reduce anxiety and depression.
The methylation pathway also makes a compound called BH4 which is important for the production of serotonin, our happy neurotransmitter, and dopamine, our reward neurotransmitter.
The methylation pathway helps clear something called homocysteine, which can contribute to symptoms of anxiety when it is too high.
Methylation is also required for detoxification. Buildup of toxins can impact our mental health.
COMT
COMT stands for catecholamine methyltransferase, which is the name of an enzyme that breaks down dopamine, epinephrine, and norepinephrine in the brain. These neurotransmitters are responsible for reward sensation and stress response. COMT variants are some of the most common I see contributing to anxiety in clinical practice. Common COMT variants are down-regulations, meaning the enzyme breaks down neurotransmitters slower than it should. These higher levels of neurotransmitters can create anxiety and hyperactivity. They can also create things like racing mind, increased focus, high performance, and perfectionism. However, because there are so many of these neurotransmitters hanging around, your brain slows synthesis of them. This depletes your reserves of these neurotransmitters, causing you to be less resilient to stress and more susceptible to depression. With COMT variants, you may experience anxiety and depression in cycles. Magnesium and SAM-e help COMT run faster.
OXTR & Empathy
Ever felt like you are an empath? As an empath, you may find yourself extremely sensitive to the emotions and environment around you. You may unconsciously pick up on things other people are feeling but not saying, and internalize those emotions as your own. Being an empath can be a special gift, but it can also be exhausting. Believe it or not, there is a real biological basis to this! OXTR stands for oxytocin receptor. It is responsible for regulating the actions of oxytocin in our bodies, a powerful chemical for feeling bonded. However, OXTR variants can also impact the way our bodies utilize serotonin, our happy hormones. When you have OXTR variants, you may be more empathic, causing you to use your serotonin more quickly. I have seen biological empaths have difficulty getting in touch with their emotions, have compulsive behaviors, or having defiant behaviors because they do not know how to process the way the world around them is impacting them. Without lifestyle boundaries, this can lead to low serotonin levels, which are associated with depression, overwhelm, cravings, weight gain, and sexual dysfunction. I see a dramatic difference clinically when supporting OXTR variants with serotonin precursors such as 5HTP.
GAD & Glutamate
When I think of anxiety, racing mind, and alertness, I think of glutamate. Glutamate is a neurotransmitter that keeps neurons in our brains firing. High levels create problems; in extremely high levels, glutamate is lethal. At non-lethal elevated levels, glutamate is toxic to the brain and imbalances in glutamate can be a trigger for seizures. The brain keeps glutamate in check by converting it to GABA. When I think of GABA, I think of calm and relaxation-that feeling you get when you are on the beach in Hawaii. The primary enzyme responsible for converting glutamate to GABA is GAD, but glutamate levels can be broken down by other enzymes and biochemical pathways as well. Variants in and of these enzymes can create excess glutamate, which presents as anxiety, racing mind, and insomnia. They can also create symptoms of low GABA such as restlessness, ruminating thoughts, muscle tension, and self medicating (for example, with alcohol). Conversion of glutamate to GABA is dependent on Vitamin B6 and magnesium and supplementation with these nutrients is often helpful in cases of glutamate imbalances. In more extensive cases of glutamate imbalance, supplementation with GABA and natural products to reduce glutamate can also be helpful.
Histamines
We usually think of histamines as responsible for creating allergic reactions. This is true, but histamine is not limited to this process. It has many other jobs as well. Histamine is also involved in digestion and central nervous system processes, such as sleep wake cycle. Have you ever taken a Benadryl or other antihistamine and felt sleepy? This demonstrates the role of histamines in wakefulness. Clearly, we want enough histamine in our bodies. However, as in the case of allergies, too much histamine is not good either; too much histamine in the brain can also promote anxiety and insomnia. There are 3 primary pathways by which histamine is broken down. Variants in the genes that create the enzymes that run any of these three pathways can create excess histamine and impact mental health. Histamines in the brain may also be upregulated by certain types of gastrointestinal infections, mold toxicity, or presence of inflammatory genetics.
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