DNA Mind: Mood Regulation

As we know, some individuals have a harder time regulating their mood and emotions than others do. This is highly connected to their genetic predisposition. Mental health falls under the neuropsychiatric disorder umbrella and accounts for up to 25% of all disability-adjusted life years. The genetic predisposition an individual has contributes to the risk of developing a mental health disorder. By using genetic testing, we have the ability to see if a patient is at risk for depressive disorder, bipolar disorder, anxiety, and PTSD. We use the DNA Mind test by DNA Life. A sample report can be seen below: 

Genes

You can see below that there are many factors that influence mood regulation throughout the brain.  Many of these genes have to do with inflammation, methylation, cell signaling, and more. Specifically, mood regulation is associated with a specific set of genes. 

The specific genes that impact mood regulation are CRP, IL-1, IL-6, TNFA, MTHFR, MTR, COMT, BDNF, IAHTR1A, FKBP5, OXTR, CACNA1Cm ANK3, and GSK3B. 

CRP

CRP is a proinflammatory marker. This binds to foreign and damaged cells and increases the amount of macrophages in the body. When it comes to regulation and protection, higher levels of CRP have been found in those who suffer from a psychiatric disorder like depression or dementia. The GG homozygote has a moderate impact, the GA heterozygote has a low impact, and the AA wildtype has no impact. 

We can see here that the G allele is the risk factor. It has been linked to chronic low-grade inflammation and depressive disorder, along with cognitive decline. For individuals who have the G allele, we want to adjust their lifestyle to ensure they are taking anti-inflammatory measures. This means that we want to decrease their inflammation as much as possible by having them take omega 3 fatty acids, controlling their weight, and having steady blood glucose levels. For more information, please refer to GeneCards, The Human Gene DataBase.

IL-1

This is one of the first genes that becomes activated when an issue with a tissue arrises in the body. Il-1 is implicated as an important leverage point in the inflammatory cascade. We see specific genetic variations in IL-1 that can lead to a higher inflammatory response. Therefore, if you are positive for IL-1, you are at an increased risk for developing chronic diseases. IL-1 positive has a moderate impact and IL-1 negative has no impact. 

If you are IL-1 positive results have been correlated with increased plasma concentrations and alpha beta gingival fluid. Additionally, they are associated with pro-inflammatory diseases such as neurodegenerative disease and mood disorders like depression. For more information, please refer to Gene Cards, The Human Gene DataBase. 

IL-6

This incodes for Interleukin 6 which is also a pro-inflammatory cytokine. This is an extremely important factor as it is responsible for the expression of CRP. We have seen that individuals with psychiatric disorders like depression and dementia have higher levels of IL-6 and CRP. Specifically, the C allele leads to increased expression and individuals with a C allele are more likely to suffer from depression and cognitive decline. 

The wildtype GG has no impact, the GC heterozygote has a moderate impact and the homozygote CC has a high impact. Patients who possess a C allele should monitor their weight, ensuring it does not get out of hand. Excess weight leads to added toxins released throughout the body. To better control weight, we recommended staying away from pro-inflammatory foods, refined carbohydrates, and transfats. Additionally, the natural supplements such as curcumin, ginger, and sulforaphane may be beneficial to these individuals. For more information, please refer to Gene Cards, The Human Gene DataBase. 

TNFA

Similar to IL-6, TNF alpha is an proinflammatory cytokine that is involved in the regulation of inflammation. We have seen that individuals who have more TNF in their blood, have depressive order and neurodegenerative disorders. In fact, those who have the A allele have a 2-fold increase in transcription, leading to increased levels circulating throughout the body. 

The wildtype GG has no impact. The heterozygote GA has a moderate impact, and the AA homozygote has a high impact. For patients who have the risk A allele, we need to make sure they focus on reducing psychosocial stress and eat an anti-inflammatory diet. We also encourage the uptake of phytonutrient rich foods and omega 3 fatty acids. For more information, please refer to GeneCards, The Human Gene DataBase. 

BDNF

BDNF stands for Brain Derived Neurotrophic Factor. This is part of the nerve growth factor family of proteins in the body. Its main purpose is to promote brain development, including neuronal cell survival, differentiation, migration, synaptogenesis, and plasticity. This gene is also hypothesized to participate in the regulation of stress in relation to neurodegenerative and mood disorders. Additionally, individuals who have altered levels are more susceptible to addictive behaviors. The wildtype CC shows no impact, the CT heterozygote shows a moderate impact, and the TT homozygote shows a high impact. 

With these genotypes, we see the risk allele is T. When the T allele is present, there is a 25% reduction in activity dependent secretion in the central nervous system. This is responsible for individuals having cognitive decline, anxiety, and addictive behaviors. In order to best help those who have the T allele, we recommend participating in regular aerobic exercise. Exercise has been proven to improve mood and reduce the risk of neurodegeneration. For more information, please refer to GeneCards, The Human Gene DataBase. 

COMT

Dopamine is the neurotransmitter that is responsible for modulating feelings of reward and pleasure. If there are alterations in dopamine, we see various psychiatric disorders, neurodegenerative disorders, cognitive impairment, mood and anxiety disorders, and addictive behavior leading to a risk-seeking behavior and substance abuse. COMT catalyses the transfer of methyl groups. This is important when it comes to the metabolism of endogenous substances. The wild type, GG shows a high function impact. The heterozygote GA shows moderate function and the homozygous AA shows low function. 

Individuals with the GG genotype (wild type) are at a risk for developing cognitive deficits and cognitive decline. This is related to the increased enzymatic activity leading the dopamine to be broken down faster. GG genotypes also have a higher susceptibility to chase reward-seeking behaviors. It is best to encourage those with a GG genotype to engage in social activity and learning new hobbies to keep the cognitive decline to a minimum. 

If you have the AA genotype (homozygotes) you have lower enzymatic activity. This leads to the decreased breakdown of neurotransmitters and increases your susceptibility to anxiety disorders. Additionally, the AA carriers are more likely to have bipolar disorder and depression. These individuals should avoid environmental stressors and should limit caffeine and alcohol while increasing their magnesium intake. For more information, please refer to Gene Cards, The Human Gene DataBase. 

MTHFR

Methylation is the process of creating methyl groups that can be donated to a molecule. B-vitamins are essential in this process. Those who have poor methylation function have also been shown to have low levels of vitamin B, enzymatic deficiencies, and psychiatric and neurological diseases. There are two polymorphisms we see. One is MTHFR C>T and the other is A>C.

C>T

The CC is the wildtype, leading to no impact. The CT is the heterozygote that has a moderate impact, and the TT is homozygote which has a high impact. We see here that the risk allele is T. When the T allele is present, it reduces the stability of the enzyme and leads to an increase of homocysteine levels. This can then cause a decrease in DNA methylation. Those who have a T allele are more likely be depressed and have bipolar disorders. It is important for these individuals to obtain an adequate amount of vitamin B and avoid alcohol and smoking. 

A>C 

The wildtype AA has no impact, the AC heterozygote has a low impact and the homozygote CC has a moderate impact. For those who have the C allele, they have a decreased enzyme, this strongly relates to depression and bipolar disorders. Similar to those who have the T allele, these individuals need a diet that is rich in B vitamins. 

For more information, please refer to GeneCards, the Human Gene DataBase.

MTR

This is a reaction that is B-12 dependent and essential to supply methionine for SAM synthesis. However, we see a common polymorphism that impacts the functionality of the site, leading to increased levels of folate and homocysteine in the blood. The wild type, AA has no impact. The Heterozygote AG has a low impact and the homozygous GG has a moderate impact. With the G allele, we see that there is increased enzyme activity. 

For those who have the risk G allele, we recommend that they consume a diet that is rich in vitamin B and decrease their intake of alcohol. The genotype associated with G alleles are more likely to have depressive order when they have a lack of vitamin B. For more information, please refer to Gene Cards, The Human Gene DataBase. 

1A HTR1A

To have the proper function of serotonin, a serotonin system and regulators are needed. 1A HTR1A is one of these regulators. It is a protein that mediates negative feedback of inhibition of serotonergic neurons and signaling in brain regions. The wild type CC has no impact. The heterozygote CG has a moderate impact, and the homozygote GG has a high impact. 

With the G allele, we see that the transcriptional repression becomes blocked. This leads to an upregulation in autoreceptor expression. For those who have the GG genotype, there is an increased risk for suicidal thoughts, panic disorder, panic symptoms, and stress responsiveness. We recommend that those with the G allele practice good stress release activity and avoid high-stress situations. For more information, please refer to Gene Cards, The Human Gene DataBase. 

FKBP5

A binding protein that modulates receptor activity in response to stress and other cellular processes in the brain. The wild type CC has no impact, the heterozygote CT has a moderate impact and the homozygote TT has a high impact. The T allele has been shown to have an increased risk for PTSD as well as depression, especially following a major stressful event. 

For those who have the T allele, it is important to practice stress management and different coping exercises. For more information, please refer to Gene Cards, The Human Gene Data Base. 

OXTR

Oxytocin is a peptide hormone and a neuropeptide. This hormone is produced by the nucleus and released during social bonding, sexual reproduction, during and after childbirth. This plays an important role in the brain. The wild type, GG shows a beneficial impact. The heterozygote GA shows a low impact and the AA homozygote shows a moderate impact. 

Those who have the GG genotype tend to relate more and have a better sense of empathy and stress reactivity. However, those with an A allele have a decreased ability to manage stressful situations and environments. These carriers need to incorporate stress management activities into their lifestyle and avoid high-stress situations. For more information, please refer to Gene Cards, The Human Gene DataBase. 

CACNA1C

“Calcium Voltage-Gated Channel Subunit Alpha 1 C”  encodes a subunit for the calcium channel. This calcium channel is held responsible for signaling the excitatory pathways in the brain. These cells play a role in generating and transmitting electrical signals. This specific gene has been associated with mood instability and bipolar disorder. The wild type GG has no impact, the heterozygote GA has a low impact, and the homozygote AA has a moderate impact. 

In fact, there have been studies shown that increased activation within this gene (A carriers) have a higher risk of developing bipolar disorder. 

For those who have the A allele, it is important to be aware and cautious of signs associated with mood disorders. Additionally, omega 3s can be used to help these individuals. For more information, please refer to Gene Cards, The Human Gene DataBase. 

ANK3

These are part of the membrane skeletal proteins and is expressed in almost all tissues. In the brain, it is dominantly expressed in the frontal cortex, hippocampus, and cerebellum. These regulate excitatory signaling and are characterized by mood instability. The wild type CC has no impact, the heterozygote CT has a moderate impact, and the homozygote TT has a high impact. With this polymorphism, we also see genotypes with A>G. For these individuals the AA wildtype has no impact, the AG heterozygote AG has a low impact and the GG homozygote has a moderate impact. 

For those who are at risk and carry the T or G allele, it is important to monitor them and watch for mood and bipolar disorders. Omega 3s can also be used to help these individuals. For more information, please refer to Gene Cards, The Human Gene DataBase. 

GSK3B

This is a protein that is involved in Wnt signaling and is a negative regulator when it comes to the homeostasis of glucose. Therefore, this protein is essential in energy metabolism, inflammation, mitochondrial dysfunction, and apoptotic pathways. For the gene impact on this genotype, if you have a neutral genotype, you have no impact. If you have an upregulated genotype, you have a moderate impact. There is an increase for depression rates for those who have a moderate impact. For more information, please refer to GeneCards, The Human Gene DataBase. 

Test Pairing

As noted, inflammation is an extremely common marker that has to do with neurodegenerative disorders. In order to best help the body and reduce inflammation, we do a food sensitivity test on our patients. The food sensitivity test we use is from Vibrant America. A sample report is shown below: 

Second, we want to measure the CRP levels in an individual to get a better understanding of where this biomarker is at. The test we use is from Genova. A sample test can be shown below: 

An important aspect of mood regulation and mental health is ensuring you are taking care of your body. This includes eating the proper nutrients, avoiding stress, regular exercise, and chiropractic care. In fact, chiropractic care has been shown to help reduce mood disorders and improve mood regulation. By using manual adjustments of the upper cervical spine, patients have reported less manic episodes, less migraines, and less headaches with improved sleep quality. More can be found by reading, “Treatment of Bipolar, Seizure, and Sleep Disorders and Migraine Headaches Utilizing a Chiropractic Technique”. 

 

When it comes to mood, there are so many outside environmental factors that contribute. However, knowing how you handle situations at the core is always a great way to prepare yourself for situations that may arise. I tend to not handle stressful environments well, but knowing that my genetic makeup is predisposed to this, it allows me to take a breath, calm down, and handle the situation in the best way possible rather than becoming overwhelmed by stress. -Kenna Vaughn, Senior Health Coach 

References: 

Erin L Elster, DC, Journal of Manipulative and Physiological Therapeutics. March-April 2004.  doi.org/10.1016/j.jmpt.2003.12.027 

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