Can This Gene Influence Your Risk of Mood Disorders (COMT)?

Cognitive-Behavioral Therapy

One of the most common forms of therapy used by mental health professionals is cognitive-behavioral therapy (CBT). The main idea behind the use of CBT in depression is to help patients change their patterns of thinking and make behavioral changes to improve coping and reduce distress [R, R].

CBT is widely used to improve both mood and anxiety disorders, with strong clinical evidence of its effectiveness. Neurobiological evidence suggests that CBT works by reducing the activity of brain regions involved in emotional processing (such as the amygdala and hippocampus) and cognitive processing (such as the prefrontal and anterior cingulate cortex) [R, R, R].

In a clinical trial on over 150 people with IBS and symptoms of depression, those with the ‘AA’ genotype benefited the least from CBT in terms of mood improvement and pain relief [R].

CBT is widely used as a standard treatment for mood disorders. Your COMT variant may determine your rate of success.

Exercise

People who engage in regular physical activity experience fewer depressive and anxious symptoms. Both aerobic (e.g swimming) and anaerobic (e.g. weight training) exercise effectively lower depression and enhance mood [R, R, R].

In a small trial on 14 women with depression, an aerobic exercise program (45-50 min/session 3x/week for 16 weeks) reduced COMT activity [R].

Regular physical exercise reduces depressive symptoms. Its effects on COMT activity may contribute to this benefit.

Light Therapy

“Light therapy” typically involves placing a “light box” (usually with a brightness of about 10,000 lux) nearby for 30 minutes each morning shortly after waking up. Light therapy has been reported to be especially effective for seasonal affective disorder (“SAD”), as the bright artificial light offsets the lack of sunlight that people often experience during the winter months [R].

For instance, bright light therapy reduced the symptoms of winter seasonal depression in a clinical trial on 99 people. This therapy may also help with non-seasonal depression, as seen in another trial on 122 people [R, R].

In a clinical trial on 87 people with bipolar disorder in their depressive phase, light therapy (combined with sleep deprivation) was less effective at improving mood in those with the ‘GG’ genotype at rs4680 [R].

Light therapy is especially effective for seasonal affective disorder. The effectiveness of this therapy may depend on your COMT genotype.

Sufficient Folate Intake

Folate (vitamin B9) is an antioxidant vitamin with key roles in cellular metabolism, blood cell production, immune response, brain development and function, and fertility [R, R, R, R, R].

This vitamin restores SAM-e levels by producing its precursor methionine from the amino acid homocysteine. Folate is also involved in the synthesis of serotonin and dopamine. An imbalance in these neurotransmitters can lead to the development of depression and anxiety disorders [R, R].

According to one meta-analysis, depressed patients have lower folate levels and lower dietary intake of this vitamin. In four trials of over 590 patients with depression, folic acid had a stimulatory effect on serotonin receptors in the brain and improved responsiveness to antidepressants [R, R, R, R].

Increasing folate levels in 22 people with eating disorders led to significant improvements in depressive symptoms [R].

Food sources of this vitamin include green leafy vegetables, citrus fruits, and legumes [R].

Folate is an antioxidant vitamin with key roles in cellular metabolism, immune response, brain function, and fertility. Abundant evidence associates deficiencies in this vitamin with depression.

Extra Virgin Olive Oil

Olive oil consumption is associated with reduced depression rates. In a study on over 1300 healthy volunteers, peole eating a Mediterranean diet with olive oil had lower depression scores [R, R].

Extra virgin olive oil is rich in phenolic compounds. One of them, oleacein, is a catechol-containing compound with the potential to inhibit COMT [R].

Olive oil consumption is associated with reduced depression rates. Its phenolic compound oleacein inhibited COMT in test tubes.

SAM-e

SAM-e, the primary “methyl donor” used to activate the COMT enzyme, is classified as a supplement in the US and a prescription drug in some European countries.

SAM-e is one of the most studied complementary treatments for depression; extensive clinical reviews have documented its safety and efficacy. It acts faster than common antidepressants and yields similar results [R, R, R].

A large evidence-based database, Cochrane, reviewed eight clinical trials with over 900 depressed patients. They concluded that SAM-e works as well as antidepressant drugs and noted its excellent safety profile. However, neither of the treatment options was significantly better than placebo [R].

In a recent study of 60 patients with mild-to-moderate depression, a combination of SAM-e and vitamin B complex improved symptoms while causing no side effects [R].

According to four studies with over 170 patients, SAM-e (800-1,600 mg daily) can even combat drug-resistant depression when added to standard treatment. It provided significant improvement in 35-60% of the patients [R, R, R, R].

Importantly, the health authorities advise against combining SAM-e with antidepressants due to potential drug interactions [R].

SAM-e is the methyl donor required for COMT activity. As a supplement, it has been widely investigated as a complementary treatment for depression.

St. John’s Wort

A systematic review of over 35 studies and almost 7000 patients found St. John’s wort effective for the treatment of depression. The review also associated St. John’s wort use with fewer adverse effects compared to conventional antidepressants (such as SSRIs) [R].

Similarly, a review of 27 studies and over 3800 patients found St. John’s wort to be as safe and effective as SSRIs for mild-to-moderate depression [R].

Its extract and active compound hypericin inhibited COMT and another enzyme that also breaks down catecholamine neurotransmitters (MAO) in test tubes, possibly explaining the antidepressant effects of this herb [R].

St. John’s wort is a well-known herbal remedy for depression. Its ability to inhibit COMT may account for this effect.

Passionflower

Passionflower contains indole alkaloids, which can boost the levels of essential neurotransmitters in the brain, such as dopamine, serotonin, and noradrenaline. This feature makes them promising candidates for the development of new antidepressants [R, R].

The species of passionflower that produces “passion fruit” (P. edulis), relieved the symptoms of depression in mice by raising the levels of serotonin and dopamine [R, R].

In a study in mice, the extract of another passionflower species (P. incarnata) also increased dopamine levels and inhibited COMT [R].

Preliminary research in animals suggests that passionflower may help with depression, possibly by inhibiting COMT.