energy & fatigue

SLC6A4

Can Disrupted Serotonin Signalling Cause Fatigue? (SLC6A4)

Written by Jasmine Foster, BSc, BEd on November 9th, 2020

SLC6A4 encodes a serotonin transporter that changes the length and strength of serotonin signals. Do you have risk alleles? Find out here.

SLC6A4 and Chronic Fatigue Syndrome

SLC6A4 encodes a serotonin transporter protein. Once serotonin has been released by brain cells, SLC6A4 becomes active and moves the serotonin back into those cells. In this way, SLC6A4 reduces the length of serotonin signals [R, R].

This gene has mainly been associated with how a person responds to antidepressants like citalopram [R].

Citalopram is a selective serotonin reuptake inhibitor (SSRI), meaning that it works by keeping serotonin in the space between brain cells for longer before it moves back into the cell. In other words, it prevents the “reuptake” of the serotonin into the brain cell that released it. Since SLC6A4 is part of the serotonin reuptake mechanism, it makes sense that it may affect how well a drug like citalopram works [R, R].

Impaired SLC6A4 gene function correlates with chronic fatigue syndrome (CFS). Some research suggests that SLC6A4 variants may increase the brain’s sensitivity to certain environmental changes; people with these variants are more likely to become anxious, but also respond more positively to good things happening [R, R].

So, while people with altered SLC6A4 function may develop CFS at higher rates, they may also respond more positively to certain management strategies [R, R].

SLC6A4 encodes a serotonin transporter that changes the length and strength of serotonin signals. Variants in this gene have been associated with chronic fatigue syndrome and response to some medications.

Your SLC6A4 Results for Chronic Fatigue Syndrome

SNP Table

variant	genotype	frequency	risk allele
rs2066713
rs140701

SLC6A4 rs2066713 [R]

‘G’ = Associated with higher rates of chronic fatigue syndrome
‘A’ = Possibly protective against chronic fatigue syndrome
The ‘G’ allele may increase the brain’s sensitivity to both good and bad environmental changes [R, R].

SLC6A4 rs140701 [R]

‘C’ = Not associated with chronic fatigue syndrome
‘T’ = Associated with higher rates of chronic fatigue syndrome
The ‘T’ allele may increase the brain’s sensitivity to both good and bad environmental changes [R, R].

Recommendations

Stress Management

Stress causes the release of the stress hormone cortisol which, in turn, appears to change the brain’s sensitivity to serotonin signaling [R].

People with SLC6A4 variants are more sensitive to stress, but also more likely to benefit from positive experiences. Thus, stress management strategies are essential for managing CFS [R, R].

Stress and fatigue are closely and reciprocally linked, meaning they often co-occur and can influence each other. Stressful life events can 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 signaling.

Exercise

Exercise has the potential to relieve stress, in part by balancing serotonin and other neurotransmitters in the brain [R].

A sedentary lifestyle is a common cause of persistent fatigue. In many clinical studies, exercise boosted energy levels in people with chronic fatigue syndrome, cancer, arthritis, and more [R, R, R, R, R, R, R].

Practice regular moderate-intensity exercise and avoid a sedentary lifestyle to lessen the impact of your variants on fatigue.

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. Thus, sufficient vitamin D intake can help balance serotonin in the brain [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 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) Surprising Link Between Glutamate & Fatigue (BDNF) The Complement Cascade in Chronic Fatigue Syndrome (CFB)

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