sleep

energy & fatigue

HTR2A

The Role of Serotonin in CFS & Fibromyalgia (HTR2A)

Written by Jasmine Foster, BSc, BEd on November 4th, 2020

HTR2A encodes a type of serotonin receptor that can actually decrease serotonin signalling. What is its role in CFS & fibromyalgia? Find out here.

Summary

HTR2A encodes one type of serotonin receptor. Variants of HTR2A may play a role in chronic fatigue syndrome and fibromyalgia by reducing available serotonin. Lifestyle, diet, and supplement modifications may counteract the effects of these variants by supporting serotonin signalling.

HTR2A and Fatigue Disorders

The HTR2A gene helps produce a serotonin receptor, 5HT2A [R].

Serotonin plays an important role in the brain, where its main job is to transmit messages between nerve cells. According to some scientific theories, serotonin—which is sometimes known as the “happiness hormone”—is involved in all aspects of human behavior [R, R].

5HT2A receptors are commonly found in brain cells, as well as in other parts of the body including platelets, the heart, joints, immune cells (monocytes), and the vagus nerve [2, 3].

These serotonin receptors are found throughout the brain, but studies suggest that they are concentrated in the prefrontal cortex, amygdala, and hippocampus — areas implicated in learning, memory, and overall cognitive ability [R, R, R, R, R].

Some researchers hypothesize that 5HT2A receptors decrease with age. The activity of these receptors may also follow the circadian rhythm, becoming more or less active during certain parts of the sleep-wake cycle [R].

Serotonin and its receptors have been implicated in the development of chronic fatigue syndrome (CFS) and fibromyalgia. People with these conditions may have a higher than normal concentration of one type of 5HT2A receptor (postsynaptic receptors) that actually reduces serotonin signaling overall [R, R].

One variant in the HTR2A gene has been associated with higher rates of both CFS and fibromyalgia. Unsurprisingly, this variant probably increases postsynaptic 5HT2A receptor concentration and decreases overall serotonin signalling [R, R].

Serotonin, an important neurotransmitter for all aspects of human behaviour, plays an important role in the sleep-wake cycle. A dysfunctional serotonin system may contribute to chronic fatigue syndrome and fibromyalgia.

Your HTR2A Results for Fatigue Disorders

SNP Table

variant	genotype	frequency	risk allele
rs6313

HTR2A rs6313 [R]

‘G’ = Associated with increased rates of fatigue disorders (CFS and fibromyalgia)
‘A’ = Possibly protective against fatigue disorders (CFS and fibromyalgia)

Recommendations

Stress Management

Genetic variants of the HTR2A gene may impair BDNF levels in the brain, causing an increase in cortisol and anxiety as a result. Cortisol, in turn, appears to decrease serotonin signalling [R].

Stress and fatigue are closely and reciprocally linked, meaning they often co-occur and can influence each other. Stressful life events may cause not only PTSD, but also chronic fatigue syndrome. Similarly, occupational exposure to traumatic events of others (e.g., by healthcare workers) causes physical and mental fatigue, and may reduce empathy [R, R, R, R, R].

Cognitive-behavioral therapy (CBT) for stress management has been reported to reduce fatigue from chronic fatigue syndrome, fibromyalgia, and multiple sclerosis in several studies. Similarly, its combination with mindfulness meditation (mindfulness-based stress reduction) may help with fatigue from fibromyalgia and cancer [R, R, R, R, R].

Relaxation therapy with breathing practices and muscle relaxation exercises has also been reported to help with fatigue from conditions such as chronic fatigue syndrome, multiple sclerosis, cancer, heart failure, and stem cell transplantation. However, CBT was more effective in those studies that compared both treatments [R, R, R, R, R, R, R, R, R].

Psychological stress releases cortisol in the brain, which in turn may decrease serotonin signalling.

5-HTP

In the body, serotonin is made from 5-hydroxytryptophan (5-HTP), and 5-HTP is made from L-tryptophan. Therefore, increasing the levels of either of these “building blocks” (metabolic precursors) can, in theory, lead to increased overall levels of serotonin [R].

Limited research suggests that taking L-tryptophan may raise plasma serotonin, and may improve certain cognitive, motor, or gut issues in those who are deficient [R, R].

In a small clinical trial of people suffering from fibromyalgia, supplementation with 5-HTP improved fatigue and other symptoms of the condition in half of the patients [R].

5-HTP is one of the major building blocks of serotonin, and supplementing with it may improve the symptoms of fibromyalgia.

Vitamin D

Vitamin D helps the body make, release, and use serotonin, including in the brain by activating an enzyme that converts tryptophan into serotonin. If vitamin D levels are low, our brains make less serotonin. Thus, increasing vitamin D intake may increase serotonin levels, thereby potentially supporting mental health [R, R].

Many studies have associated vitamin D deficiency with fatigue and muscle weakness, although not all people with this deficiency experience these symptoms [R, R, R, R].

Unsurprisingly, correcting vitamin D deficiency with supplements improved fatigue in both healthy people and those with various diseases [R, R, R, R, R].

Vitamin D is required for the body to produce serotonin, and vitamin D deficiency has been linked with fatigue and muscle weakness.

Jasmine Foster

BSc, BEd

Jasmine received her BS from McGill University and her BEd from Vancouver Island University.

Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.

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 sleep blogs

Circadian Rhythms, Obesity, and Weight Loss (CLOCK) A Gene That Controls When You Want to Eat (NPAS2) Can the Happiness Hormone Keep You From Feeling Tired? (DRD2) The Role of Serotonin in CFS & Fibromyalgia (HTR2A) Dysregulated Sleep-Wake Cycles & Fatigue (TPH2) A Chemical Messenger With Dual Roles in Fatigue (DRD3)

More energy & fatigue blogs

Does This Gene Influence Your Sleep Quality And Attention Span? (ADA) Can the Happiness Hormone Keep You From Feeling Tired? (DRD2) Opioid Involvement in Fatigue (OPRM1) The Role of Serotonin in CFS & Fibromyalgia (HTR2A) Dysregulated Sleep-Wake Cycles & Fatigue (TPH2) The Fight or Flight Response in Chronic Fatigue Syndrome (ADRA1A) Can This Adrenaline Gene Prevent Chronic Fatigue? (ADRB2) A Chemical Messenger With Dual Roles in Fatigue (DRD3)

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Summary HTR2A and Fatigue Disorders Your HTR2A Results for Fatigue Disorders

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