Mechanism

• AA=lower levels of COMT protein, higher dopamine levels in the prefrontal cortex (brain).
• GG=higher levels of COMT protein, lower dopamine levels in prefrontal cortex (brain).

A (minor) allele is associated with: 

• increased risk of cocaine dependence (R).
• Gets more pleasure out of life – AA's had twice the positive emotion towards a pleasant event than GG's. GG people subjectively viewed a very pleasurable event on the same level that AA would view a slightly pleasurable event. (R) AG had a mid -level (R).
• More Creative (divergent thinking fluency – more of an effect with other genes). Dopamine in the Prefrontal cortex promotes cognitive stability by being more resistant to distractions.(R)
• Higher IQ (tested in people with schizophrenia). (R)
• Better working memory. (R, R2) – increased activation in the right brain for healthy adults with AG and AA compared to GG. (R) Also better verbal working memory (letter-number sequencing) in AA and AG compared to GG. (R)
• Better reading comprehension (R)
• More plasticity in older age – better responses to N-back brain training (R).
• Better cognitive function when not under stress: Better attention and processing of information (R). The FAB exam tests executive function: GG scored an average of 16.0, GA15.7, and AA 15.3 (R).
• More Exploratory (R).
• Better response to placebos (R). Dopamine is thought to link to reward and 'confirmation bias' which enhance the sense that the treatment is working. The response of patients with AG fell in the middle.
• Higher cognitive stability but comparatively low cognitive flexibility (R).
• Increased verbal fluency for males (but decreased it for females) (R).
• Better fine motor skills (AA vsGG) (control of small muscles in the fingers for grasping and manipulation) (R).
• Better ability to Aim (R).
• AA's focus more when they realize they have made an error (R).
• Better absorption of tea polyphenols/EGCG (R).
• AA's had a lower risk for alcoholism (R).
• AA's had Better response to paxil/paroxetin (R).
• Worse handling of stress orpain (R). Researchers found when viewing unpleasant pictures, the startle response of women with AA was about six times stronger compared to those with only one A or none at all (R).

• More Anxiety: Studies have correlated AA allele with OCD, panic disorder, phobic anxiety (R, R2).
• Lower emotional resilience/ more negative emotions/ less able to handle negative events well.
• More impulsive (AA vs GG) (R). More significant in people who had AA for this gene AND TT for (R).
• More depression –but relationship is complex (R).
• Less Cooperative, Helpful and Empathic (AA, in females) (R).
• Less Extroverted (R).
• More neurotic (trended) (R).
• Higher Homocysteine– 10.4% in AA (R).
• Higher sensitivity to mercury – boys (but not girls) with AA had impaired cognitive performance when exposed to mercury (R).
• Fibromyalgi: people with AA showed higher sensitivity to heat and pressure pain stimuli (R).
• Possible decreased risk of breast cancer risk. Asian-American women who have AA or one A who also drink black or green tea appear to have a decreased chance of developing the disease.(R)
• A= 44% Increased risk for cocaine dependence.

G (major) allele is associated with:

• Better handling of stress and pain (R).
• More Cooperative, Helpful and Empathic (GG, in females) (R).
• Higher emotional resilience/able to handle negative events well.
• Increased verbal fluency for females (also decreased for males) (R).
• Better working memory and higher hippocampal volume – in healthy chinese (R).
• GG deprived of sleep responded well to modafinil in terms of improved vigor and well-being, and maintained baseline performance with respect to executive functioning. AA individuals barely responded to the drug at all (R).
• Can more easily be hypnotyzed (R).
• GG results in more methylation in the gut (R).
• Less pleasure out of life– AA's had twice the positive emotion towards an event than GG's. GG people subjectively viewed a very pleasurable event on the same level that AA would view a slightly pleasurable event (R).
• Lower IQ (tested in people with schizophrenia) (R).
• Worse executive function/ processing information, but better under stress (R). 
• Worse fine motor skills (AA vsGG). (R)
• Less Exploratory (R).
• More childhood depressive symptoms for GG (R).
• 2X Increased risk for breast cancer (R).
• GG has 11X Higher risk of getting schizophreniform disorder from smoking marijuana as a teenager. AG has a 2.5X likelihood. (R).
• Increased risk for endometrial cancer (R).
• G alleles had a worse response to paxil/paroxetin (R).

Mechanism

• Lower activity levels of COMT protein, higher dopamine levels in the prefrontal cortex (brain) (AA)
• Higher activity levels of COMT protein, lower dopamine levels in the prefrontal cortex (brain) (GG)
• COMT stands for "catechol-O-methyltransferase" and is a protein that breaks down certain neurotransmitters and hormones
• In the brain, COMT breaks down dopamine and norepinephrine at different rates depending on its genotype. This affects how much of these neurotransmtters are around
• In the body, COMT breaks down varied compounds, including hormones similar to estrogen 

The Worrier (A)…Lower COMT, Higher Dopamine (Met)

AA is considered the 'risk' or 'bad' allele in part because people don't do well with stress and because lower COMT can create issues with methylation and not breaking down estrogen byproducts (catechol estrogens).

AA's get more pleasure out of life but also more misery (bigger high's and low's).

The Good

• Gets more pleasure out of life –  AA's had twice the positive emotion towards a pleasant event than GG's.  GG people subjectively viewed a very pleasurable event on the same level that AA would view a slightly pleasurable event. AG had a mid-level. The effect for this was "quite large". (R)
• More Creative (divergent thinking fluency – more of an effect with other genes).  Dopamine in the Prefrontal cortex promotes cognitive stability by being more resistant to distractions. (R)
• Higher IQ (tested in people with schizophrenia). (R)
• Better working memory. (R, R2) –  during an N-back task and a go-no-go task there was increased activation in the right posterior cingulate cortex for healthy adults with AG and AA compared to GG. (R) Also, better verbal working memory(letter-number sequencing) in AA and AG compared to GG. (R)
• Better reading comprehension (R)
• More plasticity in older age – better responses to N-back brain training. (R)
• Better cognitive function when not under stress: Better attention and processing of information (executive function). (R) However, realize that this one gene only accounts for 4% of the difference in executive function.  The FAB exam tests executive function.  GG scored an average of 16.0, GA 15.7 and AA 15.3.  These scores are statistically significant, but not large.
• More Exploratory (R)
• Have a better response to placebos. (R) – Dopamine is thought to link to reward and 'confirmation bias' which enhance the sense that the treatment is working. More prominent in studies with subjective conditions such as pain and fatigue rather than objective physiological measurements. The response of patients with AG fell in the middle.
• Higher cognitive stability? but comparatively low
  cognitive flexibility. (R)
• Increased verbal fluency for males (but decreased it for females). (R)
• Better fine motor skills(AA vs GG) (control of small muscles in the fingers for grasping and manipulation). (R)
• Better ability to Aim. (R)
• AA's focus more when they realize they have made an error.
• Better absorption of tea polyphenols/EGCG. (R)
• AA's had a lower risk for alcoholism. (R)
• AA's had a better response to paxil/paroxetin. [R]

The Bad

• Worse handling of stress or pain.  Researchers found when viewing unpleasant pictures, the startle response of women with AA was about six times stronger compared to those with only one A or none at all. (R)
• Anxiety: Studies have correlated AA allele with OCD, panic disorder, phobic anxiety. (R, R2)
• Lower emotional resilience/more negative emotions/less able to handle negative events well.
• More impulsive (AA vs GG). (R) More significant in people who had AA for this gene AND TT for rs6313. (R)
• More depression – but the relationship is complex. (R)
• Less Cooperative, Helpful and Empathic (AA, in females) (R)
• Less Extroverted (R)
• More neurotic (trended). (R)
• Higher Homocysteine – 10.4% in AA. [R]
• Higher sensitivity to mercury – boys (but not girls) with AA had impaired cognitive performance when exposed to mercury. (R)
• Fibromyalgia people with AA showed higher sensitivity to heat and pressure pain stimuli (R)
• It has also been linked with breast cancer risk — Asian-American women who have an AA or one A who also drink black or green tea appear to have a decreased chance of developing the disease. (R)
• 44% Increased risk for cocaine dependence. [R]
• boys with TT had worse cognitive performance when acutely exposed to mercury. (R)

The Warrior (G)…Higher COMT, Lower Dopamine (Val)

The Good

• Better handling of stress and pain. [R]
• Better at learning languages. (R)
• More Cooperative, Helpful and Empathic (GG, in females) (R)
• Higher emotional resilience/able to handle negative events well. [R]
• Increased verbal fluency for females (also decreased for males). (R)
• Better working memory and higher hippocampal volume – in healthy Chinese. (R) As you can see AA is not always smarter than GG and it depends on other factors.
• GG deprived of sleep responded well to modafinil in terms of improved vigor and well-being and maintained baseline performance with respect to executive functioning.  AA  individuals barely responded to the drug at all. [R]
• Can more easily get into hypnosis. [R]
• GG results in more methylation in the gut (R).

The Bad

• Less pleasure out of life – AA's had twice the positive emotion towards an event than GG's.  GG people subjectively viewed a very pleasurable event on the same level that AA would view a slightly pleasurable event.
• Lower IQ (tested in people with schizophrenia) (R)
• Worse executive function/processing information, but better under stress. However, realize that this one gene only accounts for not more than 4% of the difference in executive function.  The FAB exam tests executive function.  GG scored an average of 16.0, GA 15.7 and AA 15.3.  These scores are statistically significant, but not large. [R]
• Worse fine motor skills (AA vs GG) (control of small muscles in the fingers for grasping and manipulation). (R)
• Less Exploratory (R)
• More childhood depressive symptoms for GG. (R)
• 2X Increased risk for breast cancer. (R)
• GG has 11X Higher risk of getting schizophreniform disorder from smoking pot as a teenager.  AG has a 2.5X likelihood.  However, a later study did not support these findings. (R)
• Increased risk for endometrial cancer.