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TPH2

A Chemical-Producing Gene and Its Link to Anxiety (TPH2)

Written by John Williams, B.Sc on September 25th, 2020

The gene TPH2 causes serotonin to be made in the brain, leading to higher GABA levels. Some variants produce less of these chemicals, making them more prone to anxiety. Read on to find out what you can do about it.

Summary

TPH2 encodes the protein responsible for making serotonin in the brain. Variants of TPH2 play a role in anxiety by causing less serotonin to be produced. Serotonin and GABA are both associated with anxiety and their levels seem to be related. Lifestyle, diet and supplement modifications can therefore counteract the effects of these variants by increasing serotonin or by increasing GABA.

TPH2 and Anxiety

The TPH2 gene encodes tryptophan hydroxylase 2, a protein that is needed to make serotonin in the brain. Some variants will result in less TPH2 being produced and therefore less serotonin as well. Low serotonin levels are associated with anxiety [R, R, R].

SSRIs, which are drugs that increase serotonin levels by preventing serotonin from going back into your cells, seem to result in higher GABA levels. The rs4570625 TPH2 variant with higher serotonin levels also has higher GABA levels, suggesting that one way serotonin can help with anxiety is through GABA [R, R].

Your TPH2 Results for Anxiety

SNP Table

variant	genotype	frequency	risk allele
rs4570625
rs1386494

Primary SNP:

TPH2 rs4570625

‘G’ = associated with an increased risk of panic disorder and anxiety
‘T’ = no association with panic disorder or anxiety

A study also showed that the 'T' variant is associated with higher GABA levels in the prefrontal cortex, the part of the brain responsible for thinking and planning. GABA is a chemical that makes your brain less active so it makes sense that it is lower in the 'G' variant [R].

Other Important SNPs:

TPH2 rs1386494

‘T’ = associated with an increased risk of panic disorder (in women)
‘C’ = no association with panic disorder

Recommendations

Lifestyle

Meditation

Many different kinds of meditation are associated with reduced anxiety. Mindfulness meditation both increases levels of serotonin and reduces anxiety symptoms. This can be especially useful since certain TPH2 variants produce less of the protein responsible for making serotonin [R, R].

Similar effects on anxiety were found for transcendental meditation and qigong meditation as well as meditation/exercise hybrids like yoga and taichi. For maximum benefit, it is important that you perform the meditation on a regular basis [R, R, R. R].

Meditating on a regular basis may help reduce anxiety.

Diet

Magnesium

Some studies have suggested that magnesium may provide an anxiety-related benefit. One of the effects of magnesium is to stimulate GABA release, and high GABA levels are associated with reduced anxiety as GABA is mainly responsible for turning things off in your brain [R, R, R, R].

Magnesium can be taken as a supplement or added to your diet. Good sources of magnesium in your diet include nuts and leafy, green vegetables, with spinach providing a particularly high amount [R].

The relatively higher magnesium levels found in nuts and leafy, green vegetables may improve anxiety levels.

Supplements

L-theanine

L-theanine is an amino acid that was discovered in green tea. Some studies have found that L-theanine is associated with a decrease in anxiety. Animal studies have shown that L-theanine causes both GABA and serotonin levels to go up. Given that both GABA and serotonin are low in the TPH2 variants we have mentioned in this article, supplementing with L-theanine may provide some benefit [R, R, R, R, R].

Consider supplementing with L-theanine as it may help with anxiety.

5-HTP

5-hydroxytryptophan (5-HTP) is an amino acid that serves as a precursor for the biosynthesis of serotonin and melatonin in the brain from the amino acid tryptophan [R].

In a small study of 15 young adults who suffer stress or anxiety from unreciprocated romanticism, 6-weeks of supplementation with 5-HTP decreased anxiety by 3 weeks. The authors attributed the positive results to increased BDNF and serotonin levels [R].

24 people who suffered from chronic panic attacks, due to lower availability of serotonin in the brain, found significant relief after taking 200 mg of 5-HTP [R].

In clinical trials, herbal extracts of 5-HTP were shown to activate GABA receptors or increase GABA levels, promoting a sense of relaxation and decreased anxiety [R].

The body uses 5-HTP to produce serotonin. Supplementing with it may compensate for low TPH2 activity by increasing the availability of serotonin precursors.

John Williams

B.Sc

John received his BSc from the University of Toronto. John has spent the last several years teaching high school science and math to English-language learners, which has forced him to learn how to simplify difficult concepts as much as possible. He has also worked in two different research labs and has experience as a student intern working and studying under doctors in hospitals and clinics to help diagnose and treat patients, interpret lab results and fill out mountains of paperwork.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

More mental health blogs

How to Be a Better Dater (HTR2A) How to Increase Your Chances of a Romantic Relationship (5HT1A) Are You Genetically Vulnerable to High Brain Histamine, Migraines, or ADHD? (HNMT) Protect Yourself Against Stress and Mood Problems with the Oxytocin (OXTR) Gene Beat “Brain Fog” With The Cannabinoid System (CNR1) Boost Your Cognitive Ability By Protecting Your Dopamine Neurons (LMX1A) How Emotionally Self-Aware Are You? (5HT1A) The Gene That Increases Cognitive Processing Speed by Inhibiting Inflammation (NFKBIL1) The Key Dopamine Receptor Gene That Influences Your Intelligence And Creativity (DRD2) How to Increase Intelligence and Enhance Learning (BDNF)

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