Have you wondered why an antidepressant didn’t work for you? Have you ever wondered where your anxiety is coming from and if there are natural ways to deal with it? I’ve got you covered.
According to the NIH, roughly 19% of adults reported having experienced anxiety within the past year, and more than 31% of Americans experience an anxiety disorder at some point in their lives.
What is A Neurotransmitter?
Our bodies produce chemical messengers, called neurotransmitters, that carry messages from one nerve cell to another cell in the muscles, nerves, and glands. While most people think neurotransmitters only deal with emotions and mood, the entire body depends upon the neurotransmitters functioning properly in order to run smoothly. Neurotransmitters dictate everything your nervous system controls, including sleep, digestion & elimination, breathing, heart rate, blood pressure, and hormone regulation.
Neurotransmitters deliver three kinds of messages, excitatory, inhibitory, and modulatory. Whether they are excitatory or inhibitory depends on the receptor (like a keyhole) it activates on the receiving cell.
- Excitatory – These neurotransmitters stimulate neurons to fire their messages and they include glutamate and epinephrine (adrenaline).
- Inhibitory – These slow or block transmission of neurotransmitter signaling and include serotonin and GABA.
- Modulatory – These neurotransmitters influence the effects of other neurotransmitters rather than directly activating receptors.
We can experience anxiety when we have too much excitatory activity and/or not enough inhibitory activity. And our genetics play a large part in how this plays out.
Glutamate and GABA
Although not commonly recognized as a neurotransmitter, many people have heard of glutamate before, whether as part of Monosodium Glutamate (MSG), or as the amino acid glutamine, which is found in bone broth and many functional medicine gut healing protocols (glutamine and glutamate interconvert within the body).
Glutamate is an excitatory neurotransmitter that makes the brain fire. This is great for learning and recall, but like most other things in life, too much can be a bad thing. Excess glutamate can be caused by high dietary intake, genetic predisposition, and/or slowed conversion to GABA. Whatever the cause, too much glutamate can cause anxiety, quick agitation, easy startle, and/or sleep issues. Excess glutamate might also be a possibility if you are a perfectionist; always feeling a step ahead of every conversation; are prone to impulsivity or panic attacks; or if clothing tags, bright lights, or loud noises are irritating to you. These last few are common in people with autism and that is because autism spectrum disorders have been associated with altered glutamate metabolism.
GABA is a calming neurotransmitter, just like you feel at the end of a yoga class (because yoga promotes GABA production). GABA is produced from glutamate metabolism. Weird but cool, huh?
The Genetics of Excess Glutamate and/or Low GABA
Glutamate turns into GABA via the GAD gene. If someone has genetic variants on their GAD gene, which slows down conversion, they may very well have issues converting glutamate into GABA, causing elevations in glutamate and therefore be prone to anxiety, sleep issues, or being easily agitated. One way we can support our GAD gene function is with vitamin B6. B6 is a necessary cofactor for the GAD gene to work. Interestingly, GAD1 genes are associated with heroin addiction.
Inflammation, elevated sulfites, and the heavy metals lead, aluminum, and mercury, can all inhibit glutamate’s conversion to GABA.
Another gene related to glutamate is the DAO gene, which makes the enzyme D-amino-acid-oxidase. Variants here will speed up glutamate production. Health conditions observed with this variant are: Schizophrenia, bipolar disorder, autism and Crohn’s disease.
*Pro tip: If you suffer from anxiety, you may want to omit bone broth and any supplements containing glutamine from your diet as these can promote elevations in glutamate.
Serotonin and Dopamine
Serotonin is probably the most well recognized neurotransmitter due to so many discussions about depression and antidepressants.
Made from the amino acid tryptophan, serotonin is a calming inhibitory neurotransmitter. It is involved with not only mood, but also circadian rhythm and sleep (it is a precursor to melatonin), digestion, motility, blood clotting/wound healing, and bone health. Because of this, low serotonin levels have been associated with chronic pain, slow wound healing, changes in sleep, and constipation.
*Side note: A recent study in the journal Molecular Psychiatry boldly stated that the serotonin theory of depression is not empirically substantiated by concluding that a comprehensive review of research on serotonin shows “there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity.” A companion article written by a couple of the study’s authors also stated, “We conclude that it is impossible to say that taking SSRI antidepressants is worthwhile, or even completely safe.” I personally believe, and research is indicating, that depression is actually a result of inflammation and oxidative stress. The genetic report I analyze looks at many ways inflammation manifests within the body on a root cause level. Lowering inflammation can absolutely help with mood disorders!
Made from the amino acid tyrosine, dopamine is another neurotransmitter that is involved with motivation, reward, motor control, and pleasure, as well as memory, focus, and mood. Some diseases associated with dopamine imbalances are Parkinson’s, schizophrenia, and addictions.
A really cool substance called BH4 (which stands for tetrahydrobiopterin) takes the amino acids tryptophan and tyrosine and converts them into serotonin and dopamine, respectively. When serotonin and/or dopamine levels are low, people reach for pharmaceuticals (SSRIs or SNRIs) or try supplementing with tryptophan or tyrosine, but the issue could very well lie with inadequate BH4. Once BH4 is used to make serotonin and dopamine, it becomes BH2 and then it needs to be recycled back to BH4 in order for those important neurotransmitters to be made. We can measure neurotransmitters in the urine, and if both are low (as opposed to an imbalance between the two), then supporting BH4 may be a good idea. One natural way to support BH4 levels is with royal jelly, which contains naturally occurring BH4.
Low BH4 can lead to a boatload of inflammation (in the form of really nasty free radicals called superoxide and peroxynitrite), because in addition to making neurotransmitters, BH4 also keeps ammonia levels in the body in check. It also is critical for the production of nitric oxide, a substance so important to our health that it was called the “molecule of the year” and was the subject of the nobel prize six years later in 1998.
Genomic analysis can see where there may be issues with transport, receptor activity, or recycling of enzymes involved in the BH4 cycle, as well as serotonin and dopamine production and metabolism.
Genetics Related to Serotonin and Dopamine
There are numerous genes related to BH4, serotonin, and dopamine synthesis, transport, and metabolism (degradation and/or conversion to other substances). A few are:
- COMT – The COMT gene makes the Catechol-O-Methyltransferase (COMT) enzyme that degrades dopamine and its metabolites epinephrine and norepinephrine, as well as estrogen! Variants here cause a downregulation in activity, meaning if you have any variants in this gene, your metabolism of these neurotransmitters and estrogen may be slowed, leading to higher levels. Magnesium is an important cofactor for COMT.
- MAOA – The MAOA gene makes the Monoamine Oxidase enzyme that degrades serotonin and amines like dopamine and histamine. Variants here can slow the breakdown of these substances, leading to high/low cycling of them. This can cause mood swings, aggressive behaviors, and lower frustration thresholds.
- DBH – This gene provides the instructions for producing the enzyme dopamine β-hydroxylase that converts dopamine into norepinephrine. Variations in this gene may lead to dopamine β-hydroxylase deficiency, which may lead to a deficiency in norepinephrine. This in turn may cause difficulty with regulating blood pressure and other autonomic nervous system problems. Certain clostridia species are known to hinder the DBH enzyme functioning.
- DHFR – The Dihydrofolate Reductase (DHFR) enzyme is made by the DHFR gene and is what helps to recycle BH2 back into BH4 so that serotonin and dopamine can continue to be produced. DHFR also plays a role in two steps of converting folic acid into folate, so MTHFR is not the only gene that dictates folate status (for those people that blame everything on MTHFR).
- Histamine – Many people are not aware that histamine is considered an excitatory neurotransmitter (which is why antihistamines make you drowsy). Issues with histamine do not only manifest in the form of the typical ‘hay-fever’ type symptoms, as you can see in the chart below. Our genes determine how well we clear histamine. Histamine in excess of what the body is able to clear can cause histamine intolerance, which can lead to anxiety, insomnia, and even issues with estrogen dominance and infertility (histamine and estrogen fuel each other).
- OXTR– Oxytocin is a hormone that acts as a neurotransmitter, but it’s such a cool one that I wanted to mention it. Oxytocin receptors (OXTR gene) regulate a variety of behaviors, such as maternal bonding, boundaries, and empathy. Variants in this gene can lead to a higher sensitivity to stress, other people’s emotions, conduct disorders, and harder times creating or maintaining boundaries.
There are a whole lot more genes that I can discuss in relation to neurotransmitters, but I wanted to provide you with a glimpse of what our genes can tell us about our mood, behavior, and health.
Interested in learning about your genetic profile?
View the webinar – Deep Dive: Understanding Genetics to Build your Personalized Road to Health