The COMT-Dopamine Connection: Why Your Patient Isn’t Lazy—They’re Biochemically Flatlined

Share This Post

When a patient presents with low motivation, emotional flatness, addictive behaviours, or an inability to complete even simple tasks, it’s easy to mistake them as “non-compliant” or “uncommitted.”

But what if the problem isn’t psychological?  

What if it’s biochemical?

In clinical genomics, we now understand that fast COMT activity—driven by genetic variation—can deplete dopamine levels so drastically that it mimics the clinical presentation of apathy, depression, and even ADHD.

Meet COMT: The Dopamine Regulator

COMT, or catechol-O-methyltransferase, is a methyltransferase enzyme that breaks down catecholamines—dopamine, noradrenaline, and adrenaline. It’s also involved in oestrogen detoxification, making it a cornerstone in both mental and hormonal health.

What does fast COMT enzyme activity actually mean? 

If someone has a fast COMT, it means dopamine, adrenaline and hormones, can be broken down too quickly.

Think of it as a bucket with a hole in the bottom. No matter how much dopamine you produce, it leaks out before the body can use it effectively.

Clinical Symptoms of Fast COMT

Patients with **fast COMT** often present with:

  • Lifelong low motivation and emotional blunting  
  • Difficulty with follow-through (projects, jobs, relationships)  
  • High susceptibility to “self-medicating behaviours” (alcohol, cannabis, thrill-seeking)  
  • Poor memory or difficulty experiencing pleasure  
  • Fatigue that isn’t improved by rest  
  • A tendency to “numb out” under stress  
  • Suicidal tendencies

They are often dismissed as lazy, disengaged, or resistant to help—but what they’re really experiencing is a neurotransmitter deficit- particularly dopamine. 

Dopamine Flatlining vs. Dopamine Overflow

This is the **dopaminergic opposite** of your COMT slow, “A-type” personality patients who are intense, driven, focused, but anxious and overwhelmed.

Here’s a simplified contrast:

Feature  COMT Fast (Low Dopamine) COMT Slow (High Dopamine)
Motivation  Low  High 
Emotional Drive  Flat  Intense
Focus Poor  Laser Sharp 
Stress Tolerance Low Can cope well—until they snap
Addiction risk  High  Low 
Treatment Need  Build Dopamine  Metabolise excess Dopamine 

 

 Genetic + Environmental Interactions

Of course, genes are not destiny. 

COMT function is heavily influenced by environmental and nutrient factors including :

  • SAMe and magnesium levels in the body 
  • High stress, oestrogen dominance, inflammation can impact dopamine metabolism 
  • Methylation capacity must be considered (MTHFR, DHFR, B12 status)

Which means you can support a “leaky bucket” in two ways:

  1. Slow the leak  
  2. Fill the bucket 

But here’s the clinical trick: You must match the strategy to the patient’s SNPs—otherwise you risk overstimulating a system that’s already depleted.

Case Example: The Dad Who Got His Life Back

A 40-year-old male presents with:

  • Depression since age 13  
  • Severe alcohol use (14+ beers/day)  
  • Chronic fatigue, poor motivation, brain fog  
  • Addictive thrill-seeking (hang-gliding, fast driving)  

Genetic testing showed:  

  • COMT (fast)   
  • Low B12 markers  
  • MTHFR C677T++

Treatment focused on:  

  • Dopamine precursors- to top up the bucket
  • COMT inhibitors – to slow metabolism 
  • Niacin to reduce methylblock and anxiety
  • Gut support + inflammation reduction  
  • Lifestyle strategies to stabilise blood sugar and promote protein intake

Within one month, he had cut alcohol use by 80%, depression lifted, motivation returned, and energy increased significantly.

This is the power of using genomics in practice.

Learn How To Support People With Mental Health 

If this sparked clinical insights for you—good. This is only one piece of the mental health genomics puzzle.

At our upcoming 2-day live workshop in Perth, we’ll walk you through the important genes that you can test your patients for, impacting their neurotransmitter pathways and methylation pathways. You’ll get real-world case applications to help you confidently treat patients with anxiety, depression, OCD, addictions and more.

Functional genomics is no longer a “nice to have.” It’s the future of personalised mental health treatment—and it’s here now.

Secure Your Seat Now

Related Posts

Stir-Fried Asian Greens (with chicken or fish)
MTHFR

Stir-Fried Asian Greens (with chicken or fish)

Ingredients: 1 tsp sesame oil 1 tsp olive oil 2cm piece of ginger, grated 1 clove of garlic, crushed 1 birds eye chilli, finely chopped ...
Read More →
Healthy Homemade Chocolate
MTHFR

Healthy Homemade Chocolate

Ingredients: 1 cup  cocoa butter 1 cup  cocoa powder ½ cup  honey or to taste (using half this amount or less will make a bittersweet ...
Read More →
Are You Suffering From B12 Deficiency?
MTHFR

Are You Suffering From B12 Deficiency?

Are You Suffering From B12 Deficiency? I believe one of the most overlooked deficiencies in Australia, and probably worldwide, is B12 deficiency. [thrive_link color=’purple’ link=’https://forms.gle/wdS2uNAxDaisBDw67′ ...
Read More →
Upregulated methylation increases expression and proliferation of cancer cells??
Genes

Upregulated methylation increases expression and proliferation of cancer cells??

There is no question that the future of medicine will be in analysing a person’s genetics, with a detailed family history and addressing the genetic ...
Read More →
Broccoli Detox Soup from The Awesome Green
MTHFR

Broccoli Detox Soup from The Awesome Green

Ingredients: Serves 2 2 cups broccoli florets 2 celery stalks, finely diced 1 onion, finely diced 2 garlic cloves, crushed 1 cup greens (kale, spinach, ...
Read More →
Conditions

A Post-Pregnancy Thyroid Case Study: What Practitioners Need to Know

Postpartum thyroid dysfunction is a common yet under-recognised condition that can significantly impact a new mother’s health. The physiological and hormonal changes of pregnancy and ...
Read More →
Scroll to Top
Carolyn Ledowsky

Stay Connected!

Sign up for our monthly newsletter with current MTHFR research, health tips, recipes, special offers and news about upcoming events including Carolyn’s live Q&A.

Subscribe