COMT gene

The COMT gene provides instructions for an enzyme that regulates neurotransmitters in the brain, playing a key role in cognitive function and emotional regulation.

Normal Function

The COMT gene provides instructions for making an enzyme called catechol-O-methyltransferase. Two versions of this enzyme are produced:

• MB-COMT (membrane-bound): Chiefly produced by nerve cells in the brain.
• S-COMT (soluble): Produced by other tissues, including the liver, kidneys, and blood, to help control hormone levels.

In the brain, catechol-O-methyltransferase helps break down neurotransmitters like dopamine and norepinephrine. This is particularly important in the prefrontal cortex, a region involved in personality, planning, inhibition of behaviors, abstract thinking, emotion, and working memory. The enzyme helps maintain appropriate levels of these neurotransmitters to ensure efficient signaling.

Health Conditions Related to Genetic Changes

22q11.2 deletion syndrome

This syndrome results from a deletion of a small piece of chromosome 22, which typically contains 30 to 40 genes, including the COMT gene. People with this disorder have only one copy of the COMT gene instead of two.

• This leads to abnormal regulation of catechol-O-methyltransferase levels in the brain.
• Researchers believe this may explain the increased risk of behavioral problems and mental illness, including schizophrenia, depression, anxiety, and bipolar disorder.

Other disorders

Variations in the COMT gene are also studied in relation to mental illness in the general population. A common polymorphism, Val108/158Met, involves replacing the amino acid valine with methionine. This change affects the stability and activity of the enzyme, altering its ability to break down neurotransmitters.

• Studies on the link between this polymorphism and schizophrenia have yielded mixed results, though some suggest a slightly increased risk in people with valine at this position.
• Having valine at this position is associated with differences in thought processes, such as challenges with working memory, inhibition of behavior, and attention.
• Researchers have also studied this variation as a potential risk factor for bipolar disorder, panic disorder, anxiety, obsessive-compulsive disorder (OCD), eating disorders, and attention-deficit/hyperactivity disorder (ADHD).

It is important to note that these conditions are complex, and many genetic and lifestyle factors contribute to their development.