Understanding Stress Tolerance and Anxiety Through Genetics.
By Jared Allomong, DC
Have you ever noticed that some people handle stress well or relax easily and calm down after a stressful situation, while others constantly struggle with anxiety and ruminating thoughts? These same anxiety-laden individuals can also struggle with sleep difficulties, hormone imbalances, and a general intolerance to caffeine, stimulants, or even B vitamins.
Interestingly, these individuals have reflected these behavioral predispositions most of their lives. Many clinicians have given a basic vitamin B complex to a client to see it create an erratic reaction in their nervous system, but often there is no clear answer for why it occurred and is frequently assumed to be a detoxification reaction. We were taught that the sympathetic dominant stress-based nervous system can negatively impact our health. What does that really mean, and who is at risk?
One of the most profound benefits of chiropractic adjustment is the stimulation of a neurological chain that ultimately lowers norepinephrine.1 Norepinephrine is our primary sympathetic neurochemical that controls the resting state of the whole sympathetic nervous system. Thus, most individuals feel quite relieved and relaxed from an adjustment, but some patients are still anxious no matter what you do.
This could partially be explained through the bio-individual levels of our sympathetic neurotransmitters coded in our genetics, which can either be supported or further stressed by our life circumstances. This type of person could use specific nutritional support to optimize their genetics along with conjunctive therapies, such as massage, exercise, and meditation. Let us dive deeper into the genetics involved and how profoundly they influence our minds and our health.
Every enzyme that controls our biochemistry is created at specific gene regions within our chromosomes. Each of us has a unique set of functional variances in these enzymes created by small differences in their genes called single nucleotide polymorphisms (SNPs). These SNPs influence the morphology, affinity, and overall function of the enzymes they code for and present an inborn genetic predisposition to all kinds of characteristics. These differences make us individuals while also being very similar to our family lineage.
In the situation of an anxious or ruminating mind, a combination of variants can be within three particular genes that influence the metabolism and degradation of our neuroexcitatory chemicals. If these enzymes are running too slow, then the mind has trouble lowering our excitation state, which can result in hypervigilance, anxiousness, aggression, rumination, sympathetic dominance, and overexcitability. In many ways, it makes perfect sense that the genes controlling levels of dopamine, norepinephrine, and adrenaline influence the excitability of the mind. Over the past six years, I have personally observed a pattern of variants (SNPs) within genetic profiles that clearly indicate a strong tendency toward an overstimulated, anxious mind.
Research on SNPs is often directed at individual variants, causing a specific symptom or problem. When talking about anxiety, a more holistic view is needed by looking at a combination of possible variants within these three genes at the same time. When this is done, there is a consistent, clear clinical pattern of variants within genes related to COMT, MAO, and GAD, which are commonly observed together and are responsible for a reduction in the ability to degrade our neuroexcitatory chemicals.
Catechol-O-methyltransferase (COMT): The main enzyme that degrades catecholamines — dopamine, norepinephrine, and epinephrine.
Monoamine oxidases (MAO): A family of enzymes that degrade serotonin, dopamine, norepinephrine, and epinephrine in presynaptic neurons.
Glutamate decarboxylase (GAD): The only enzyme that catalyzes the conversion of glutamate to GABA. In essence, this enzyme converts our most stimulatory neurotransmitter into our most calming neurochemical.
One study looking at adolescents found variants in both MAO and COMT to be linked with higher aggressive behaviors and interpersonal problems when under high levels of academic pressure.2 Variants within specific locations in the COMT and MAO genes have individually been observed to influence the rate of catecholamine clearance. When they present together, there is an even stronger impact and a greater disposition for excess dopamine, norepinephrine, and epinephrine. This can even be true with more minor variants in each gene when expressed together and ultimately create a tendency toward sympathetic dominance, which can lead to adrenal fatigue. In addition to these two variants, it is very common to also observe SNPs in GAD in these same individuals.
Glutamate is the most stimulatory neurotransmitter we have and causes a state of activation/overactivation of our neurological pathways. More glutamate equals more activity, and when combined with more catecholamines, aggression and anxiety can exist. Additionally, the GAD enzyme is solely responsible for the conversion of glutamate to GABA, the most calming neurotransmitter.
Running an SNPs profile for clients experiencing lifelong anxiety, overexcitement, and stress tendencies can be truly profound because analyzing DNA raw data reveals the existence of these SNP variations. Many people do not realize that when they complete a salivary test kit with a company such as Ancestry.com, they receive more than just information about their heritage. They receive a raw data file, which can then be run through an analysis program to uncover SNPs, such as COMT, MAO, and GAD.
One thing unique about individuals exhibiting these SNPs is that a general B vitamin supplement does not always bode well for them. The folate, vitamin B12, and vitamin B6 that most supplements contain can drive up more sympathetic neurotransmitters, which these individuals struggle to metabolize correctly due to their SNPs.
On the one hand, B vitamins generally make sense for mood disorders since MTFHR variants limit methylfolate production, which also limits serotonin and dopamine formation. The lack of these neurochemicals is heavily associated with mood disorders, and adding methylfolate can be very helpful. Folate and vitamin B12 also assist in SAMe creation, which happens to be the essential cofactor for COMT activity. This chemistry explains why so many experience improved mood and decreased anxiety with the addition of folate and B12.3
On the other hand, for many with the combined variants in MAO, COMT, and GAD, the rates of neurotransmitter clearance are too slow, and additional B vitamins end up driving more catecholamines rather than clearing them. The answer is to nutritionally support the clearance of excitatory neurochemistry by addressing COMT, MAO, and GAD at the same time. This has a profound positive effect, and nutrition is the perfect solution.
Riboflavin is the key cofactor for MAO and has been shown to increase activity level.4
Magnesium is essential for COMT, GAD, glutamate receptor modulation, and GABA function.
Theanine and magnolia officinalis are unique in the fact they can decrease glutamate and norepinephrine activity directly and cross the blood-brain barrier easily.5,6
Taurine is a powerful neuroinhibitory neuromodulator that affects both glutamate and GABA activity.
The use of these nutrients in combination can provide direct relief for these variants and result in calming without sedation, perfect for daytime use. No other genetic pattern has been as consistent or provided more life changes for my clients than supporting this pattern correctly, and many clients can then resume other B vitamins without side effects.
In 2020, I created a program to teach doctors to recognize and understand various genetic patterns and support complex dysregulations efficiently and effectively in practice. For more information on these programs, please contact the author by email.
References
Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, Kolachana BS, Hyde TM, Herman MM, Apud J, Egan MF, Kleinman JE, Weinberger DR. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem humanbrain. Am J Hum Genet. 2004 Nov;75(5):807-21. doi: 10.1086/425589. Epub 2004 Sep 27. Erratum in: Am J Hum Genet. 2005 Jun;76(6):1089. PMID: 15457404; PMCID: PMC1182110.
