The body

The combination of COMT and MAO-A variants can affect mood regulation and neurotransmitter balance. Add in a DRD2 variant and you have very different phenotypes. Definition of phenotype: the expression (set of symptoms) of your genes as influenced by your epigenetic factors such as your diet, lifestyle and environment. You can change your phenotype by changing your epigenetics as this will in turn change the expression of your genes. Here is a quick breakdown of these different phenotypes. I have also included a fictional character for each one to help you see how this could play out, especially with regards to risks, predispositions , mental and physical symptoms that might present. Keep in mind, though, that the effects of these enzyme activities are also influenced by other genetic factors and environmental stressors. Personal history, stress, diet, sleep, and overall health can influence how these enzymes  impact mood and behavior. So while someone with a specific genotype could tend to lean towards a certain phenotype, it would ultimately depend on a combination of their genetic make-up, and other internal and external epigenetic factors.   When I am doing a feedback report for a genetic test, I take a look at this in connection with the client. This can be of benefit when it comes to making recommendations in how they can adjust their diet, certain lifestyle choices and habits and clean these up to help their genes express better. This also will determine what supplements will and won’t work for them. Sometimes we are not even aware of how the small choices we make each day impact our physical and mental health.   Slow COMT / Fast MAO-A / DRD2 (Wired but tired phenotype) With this phenotype, you’re likely to experience higher dopamine levels especially in the prefrontal cortex due to slow COMT. You will likely be quite good at problem solving and have better attention and focus and memory (slow COMT) but on the other hand you will probably struggle with mood stability due to low serotonin (Fast MAO-A)  The Reward factor is low, and there may be an increased risk of addictive behaviors and mood swings due to DRD2.   Fast COMT / Slow MAO-A / DRD2: ( ) You may struggle with cognitive issues like poor focus, attention and lack of motivation due to rapid dopamine depletion (fast COMT) but may find that you have greater emotional stability thanks to higher serotonin (slow MAO-A) which means you are able to cope better when under stressful situations. The Reward factor remains low, and the addiction tendency remains the same due to the DRD2.   Let’s break it down a bit further.   COMT -fast or slow The slow COMT variant (Met/Met, AA) leads to a slower breakdown of the neurotransmitters dopamine, norepinephrine and epinephrine. This can lead to higher levels in the brain, particularly the prefrontal cortex and basal ganglia,  that stick around for longer than what they should. When this happens it can lead to increased anxiety, mood swings and irritability. The fast COMT variant (val/val, GG) leads to an accelerated breakdown of the neurotransmitters dopamine, norepinephrine and epinephrine, which can lead to lower levels in the brain. This affects executive functioning like working memory, focus and attention. (also seen in inattentive ADHD)   MAO-A- fast or slow A fast MAO-A variant leads to an accelerated breakdown of the neurotransmitters serotonin, metatonin, dopamine,epinephrine and norepinephrine in the brain. Which results in lower levels of these affecting  mood, and potentially leading to anxiety, and reduced motivation and impacting sleep. A slow MAO-A variants leads to a reduced breakdown of the neurotransmitters serotonin, dopamine, and norepinephrine in the brain. Which results in higher serotonin availability. This can provide a buffer against emotional volatility and protect against anxiety or depression.   DRD2 DRD2 is a dopamine receptor located in the stratum, hippocampus, amygdala and cerebral cortex. The DRD2 gene codes the dopamine receptor DRD2.  The variant causes a reduced number of dopamine binding sites in the brain, resulting in reduced dopamine signaling which means that individuals with mutations are less sensitive to the activation of dopamine- based reward system and this makes them more likely to be predisposed to addictive behaviour. A simple example would be while some people may feel satisfied after one block of chocolate, it may require a whole slab for someone with a variant in DRD2 to feel the same sense of satisfaction which is why they often are led to overeating. They need stronger stimuli to experience the same level of reward as individuals with a normal receptor density, which is what often leads to addictive behaviors or seeking out more intense experiences.  Shopping, gaming, spending money, seeking out new experiences, trying new hobbies, or over eating are often part of the reward seeking. The DRD2 receptors play an important role in addiction and eating behaviour as they are involved in the dopamine based reward circuitry. This receptor has been associated with Parkinson’s Disease, alcohol addiction, opioid addiction, ADHD with hyperactivity and impulsivity, and binge-eating, affecting working memory.     Slow COMT / Fast MAO-A / DRD2 (Wired but tired phenotype) Greg (fictional character) has this combination. He works really hard and loves his job. In fact, he finds it hard to stop working! Greg is quite meticulous when it comes to detail and work ethic, paying close attention to small details. He can sit for long periods of time, focusing on his work without any problems. He likes things to be “just right”, perhaps even bordering on some perfectionist tendencies. However, when things don’t go his way, he finds himself reacting with annoyance and anger. Small things often annoy him, like spelling and grammatical errors. Greg finds it hard to switch off and relax. He feels the constant need to keep going. Others would describe him as a workaholic. When he isn’t working, he likes to participate in sports, go to the gym or do fun and exciting activities on the weekend like go-cart