Essential tremor (ET) is a neurological disease that causes a hand or arm to shake during activities such as writing or eating. The tremor can also progress to involve the neck, voice, jaw, or other body regions.
This article explores recent research on the neurological and genetic causes of ET.
What is an Essential Tremor?
The first noticeable symptom often with essential tremor is that writing or fine hand movements, such as when texting, are difficult due to shaking. For others, it may be first noticed when eating or pouring a drink into a glass. Essential tremor usually starts in the hand and arm, but sometimes it is first seen as an involuntary head movement or voice tremor.
While this article explains the neurological causes of essential tremors, keep in mind that for people with ET there are often huge emotional impacts from the disease. It causes anxiety, frustration, and decreased self-esteem for many, especially when it starts at a young age.
Symptoms of Essential Tremor:
An essential tremor usually starts as mild and barely noticeable, but it usually worsens over time. Estimates range from 2-5% worsening of tremors per year. Additionally, as the years progress, the tremor can spread to other body regions, including motor features and cognitive problems.[ref]
For most people, essential tremor begins with the hand or arm on one side of the body. It is usually noticed when using the hand, such as in eating, writing, lifting lightweight objects, or tying shoelaces. It can gradually progress to other parts of the body, such as a tremor in the voice or an involuntary head nodding.
ET is different from the tremor seen in Parkinson’s disease, which occurs when hands are at rest instead of in use. Plus, ET doesn’t affect walking or other movement issues also seen in Parkinson’s.
Tremors are caused by rhythmic, oscillatory movement of a body part at a constant frequency. The antagonistic muscles — think push then pull — are alternating contractions at a constant rate. It is a neurological disorder driven by changes in the neurons in the brain region that controls muscle movement.[ref]
Essential tremor (ET) has been studied for decades, but there are still elements of the cause that are not fully known.
Here’s what current research shows:
Neuroimaging studies show changes to the cerebellum (brain region) in people with ET.[ref]
Some studies show that Purkinje cells are affected. Purkinje cells are large neurons in a specific layer of the cerebellum. They are important in movement and controlling excitatory neurons.[ref]
Excess Activation: A 2020 study published in Science combined animal models, clinical data, and brain tissue from autopsies to examine what is going on in the brain with ET. The researchers found that people with ET have excessive brain wave oscillations in the cerebellum.
The 2020 study showed that patients with ET likely have excess synapses in between climbing fibers (a type of nerve cell) and the Purkinje cells in the cerebellum. Normally, excess synapses get pruned away as the brain develops into adulthood. But for ET patients, the excess synapses remain, which results in too many neuronal connections and overactivation. One specific protein – glutamate receptor delta 2 (GRID2 protein) – may hold the key (at least it seems to in mice).[ref][article]
GABA is an inhibitory neurotransmitter that ‘turns off’ neurons to keep them from firing excessively. A postmortem study on people who had essential tremor showed a decreased number of GABA-A and GABA-B receptors in a specific region of the cerebellum.[ref]
Lack of inhibition combined with excess synapses — all come together to show excess activation in the part of the brain that controls muscle movement.
What causes the changes in the brain?
So we have excess activity in the brain, causing oscillations in movement. But what triggers ET to occur?
Both genetic and environmental factors are thought to contribute to ET. Twin studies show that the genetic component is about 50-60%, which leaves a large portion due to environmental factors such as toxic exposure.[ref]
Toxic exposure: Several studies point to environmental factors that contribute to ET. Exposure to lead, harmane, pesticides, and organic solvents.[ref]
- Harmane is a β-carboline alkaloid found in animal foods. Grilling or frying increases the concentration of β-carboline alkaloids in meat. β-carboline alkaloids are also found in tobacco, alcohol, soy sauce, tabasco, toasted bread, and coffee.[ref] Harmane levels are elevated in ET patients compared to a healthy control group.[ref][ref][ref]
- Lead has been shown in animal studies to damage Purkinje cells in the brain. And a study of ET patients found that blood lead levels were high when compared to an age-matched control group.[ref]
- Pesticide exposure, especially long-term, is linked to higher odds of having an essential tremor. The study showed a more than 4-fold increase in risk for workers exposed to pesticides for 16 years or more.[ref]
- Heavy metal exposure, including mercury, manganese, and lead, are neurotoxic and linked to tremors.[ref]
These environmental toxins increase oxidative stress and thus may lead to neuronal dysfunction in the cerebellum.[ref]
Essential Tremor Genotype Report:
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Membership lets you see your data right in each article and also gives you access to the members’ only information in the Lifehacks sections.
CTNNA3 gene: encodes a cell adhesion molecule
Check your genetic data for rs12764057 (23andMe v4):
- G/G: increased relative risk of essential tremor[ref]
- G/T: slightly increased relative risk of essential tremor
- T/T: typical
Members: Your genotype for rs12764057 is —.
Check your genetic data for rs7903491 (AncestryDNA):
- A/A: increased relative risk of essential tremor[ref]
- A/G: slightly increased relative risk of essential tremor
- G/G: typical
Members: Your genotype for rs7903491 is —.
FUS gene: encodes a protein involved in exporting mRNA from the cell nucleus into the cytosol.
Check your genetic data for rs186547381 (23andMe v5; AncestryDNA):
- C/C: typical
- C/T: rare mutation linked to essential tremor[ref]
Members: Your genotype for rs186547381 is —.
SCN11A gene: encodes a sodium transporter important in the way certain neurons fire
Check your genetic data for rs138607170 (23andMe v5; AncestryDNA):
Members: Your genotype for rs138607170 is —.
LINGO1 gene: encodes a component of the neurite outgrowth inhibitor receptor, important in the way that the brain recovers from injuries and in neuronal survival
Check your genetic data for rs11856808 (23andMe v4, v5; AncestryDNA):
- C/C: typical
- C/T: slightly increased relative risk of ET
- T/T: increased relative risk of ET[ref]
Members: Your genotype for rs11856808 is —.
Check your genetic data for rs9652490 (23andMe v4, v5; AncestryDNA):
- A/A: typical
- A/G: slightly increased relative risk of ET
- G/G: increased relative risk of ET[ref]
Members: Your genotype for rs9652490 is —.
MAPT gene: microtubule-associated protein. Other mutations in this gene are linked to Parkinson’s or frontal-temporal dementia.
Check your genetic data for rs1052553 (AncestryDNA):
- A/A: typical
- A/G: increased risk of ET
- G/G: increased risk of ET[ref]
Members: Your genotype for rs1052553 is —.
TREM2 gene: encodes a protein expressed in immune cells, such as microglia in the brain.
Check your genetic data for rs75932628 R47H(23andMe v4, v5; AncestryDNA):
- C/C: typical risk
- C/T: reduced intracellular signaling, increased risk of Alzheimer’s disease, increased risk of Essential Tremor (important)
- T/T: reduced intracellular signaling, increase risk of Alzheimer’s disease, increased risk of essential tremor[ref][ref][ref][ref][ref]
Members: Your genotype for rs75932628 is —.
HTRA2 gene: encodes a serine protease localized to the mitochondria. When stimulated, HTRA2 can initiate cell death. Mutations lead to mitochondrial dysfunction due to an increased sensitivity to toxicity.[ref]
Check your genetic data for rs72470545 (23andMe v4, v5; AncestryDNA):
- G/G: typical
- A/G: rare mutation, significantly increased risk of ET[ref] (important)
- A/A: very rare, increased risk of ET or Parkinson’s
Members: Your genotype for rs72470545 is —.
MTHFR gene: encodes an enzyme that is key to converting folate for use in the methylation cycle. It is also important in some detoxification reactions.
Check your genetic data for rs1801133 (23andMe v4, v5; AncestryDNA):
- G/G: typical
- A/G: one copy of MTHFR C677T allele, enzyme function decreased by 40%
- A/A: two copies of MTHFR C677T, enzyme function decreased by 70 – 80%; Increased relative risk of essential tremor[ref]
Members: Your genotype for rs1801133 is —.
DRD3 gene: encodes a dopamine receptor
Check your genetic data for rs6280 Ser9Gly (23andMe v4, v5; AncestryDNA):
- C/C: poorer executive function (psychosis patients)[ref], increased risk of essential tremor[ref]
- C/T: increased risk of essential tremor (especially voice tremor)
- T/T: typical
Members: Your genotype for rs6280 is —.
VDR gene: vitamin D receptor
Check your genetic data for rs2228570 (23andMe v4):
- G/G: typical
- A/G: typical
- A/A: decreased risk of ET[ref]
Members: Your genotype for rs2228570 is —.
CYP2C19 gene: encodes an enzyme that is important in the phase I detoxification pathway for medications as well as for progesterone and melatonin (endogenous hormones).
Lifehacks for Essential Tremor:
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