ADHD in Children - The Brain and Catecholamines

I see a variety of scenarios of children with attention deficit and hyperactivity disorder (ADHD) walking into my office. They may have had a diagnosis and parents are looking for initial support; they may have had trials with medications with no success; and/or they may be taking medications and want to augment their health with naturopathic support. I love working with each scenario as naturopathic medicine can do so much for each individual.

I have written about the gut brain connection in the past and have such a passion in this area as it FASCINATES me just how much we have yet to uncover. Research is headed mostly in this direction when it comes to ADHD.

I want to focus on catecholamines and genetic patterns that can affect ADHD tendencies. We have known for a long time that ADHD is associated with alterations in the prefrontal cortex. This is the area of the brain that regulates behaviour (behavioral inhibition), attention over a delay, dividing attention and inhibiting distraction. 

Researchers have spent decades figuring out the ‘whys’ and, like any neurological disorder, there are multiple layers, triggers, and causes of ADHD. For a long time now, imbalances and genetic alteration of catecholamine pathways have been studied. 

How does this information translate into exploring areas of concern and treating patients with ADHD? First I’ll chat a little on catecholamines, how genes play a role, touch a little bit on testing, and lastly treatment. 

Catecholamines 

Optimal levels of catecholamines (eg. adrenaline, noradrenaline and dopamine) are needed for proper functioning of the prefrontal cortex area in the brain. For example studies showed that noradrenaline enhanced signals through certain receptors in this area that increased attention, dopamine decreased certain receptor transmission that reduced ‘noise’ allowing for more concentration, less distraction.

How Genes Play a Role

When there are single nucleotide polymorphisms (SNP - a variation in a single base pair in a strand of DNA) in genes that code for enzymes Catechol-O-methyltransferase (COMT) as well as monoamine oxidase (MAO), this reduces the function of these enzymes. These enzymes have many functions, one of which is to metabolize catecholamines. If they don't work, catecholamines then become 'trapped' i.e. catecholamine trapping. When they get trapped, agitation occurs in kids nervous systems - agitation leading to behaviours such as inattention or hyperactivity. 

Similar to glutamate, an ‘excitatory’ catecholamine. Glutamate decarboxylase (GAD) is the enzyme that runs N-methyl-D aspartate receptor (NMDA) receptors which allow for glutamate to bind to the area and activation of the brain to occur. If too much glutamate is present, neuro inflammation can occur which can lead to sleep issues and aggravation. 

Another excitatory neurotransmitter is histamine. When this is not broken down properly (four different pathways, two of which are MAO and D-amino acid oxidase (DAO), histamine sticks around in the brain and causes lack of concentration and even more research is done in the area of psychosis, anxiety and depression. I feel like most people know histamine in an allergy picture. When patients come in with seasonal allergies, hive reactions, and inattention, I will most likely work on their histamine pathways.

Testing

In some cases I like looking at what is actually going on in the body with levels of catecholamine functioning. I do this through looking at neurotransmitters or their metabolites through urine analysis.

Looking at genetic testing is often so helpful as well - this is where you can see the SNPs and what enzymes aren't functioning properly.  

Treatment

How I break treatment down in this area is to a) look at what cofactors those specific enzymes need to work in order to metabolize the catecholamines and b) how I can support specific catecholamines directly. For example vitamin B6, magnesium, and vitamin C all support COMT in its function. Vitamin B1 and B6, for example, can support GAD.

Magnesium and l theanine can inhibit the work of glutamate so as not to cause neuro inflammation. N acetyl cysteine (NAC) can aid in the central nervous system releasing glutamate as well. B vitamins and iron cofactors for tyrosine can make dopamine. And oftentimes giving giving tyrosine directly to patients works quite well (most often if patients have responded well to a stimulant pharmaceutical). 

Sometimes I'll provide methylfolate and methyl B12 and see how they do, these again are cofactors that are needed for the production of catecholamines. If these increase the agitation, then often times I'll suspect that trapping is going on (as per above).

Any questions on the above reach out! Lets connect. The other area I use a lot to support alongside of the above in the area of ADHD is anthroposophical medicine. 

PMID: 16961424

PMID: 33467150