Neurotransmitter Testing

There’s a theory—and a reasonable one—that as inflammation increases, the amount of oxidative free radicals also increases, and they eventually “spill-over” and disrupt neurotransmitter formation. 

Initially, neurotransmitter production increases in response to stressors, but over time inflammation-related free radicals will interrupt Cortisol curve neurotransmitter production, ultimately leading to depletion. Some researchers have suggested that the brain translates immune system activation much as if it were a stressor, and the neurotransmitter levels reflect the severity of the problem.

Serotonin: Serotonin directly inhibits inflammatory cytokine production, and promotes an anti-inflammatory gene expression profile, and also inhibits pro-inflammatory cytokine production.

Gamma-Aminobutyric Acid (GABA): GABA also has a role in inflammation: there are GABA receptors (GABA-Rs) on immune cells that provide convenient targets to modulate immune cell activity. Additionally, GABA acts on both T cells and macrophages to exert anti-inflammatory effects in certain diseases, including diabetes. In fact, GABA receptors have been identified on cells within the Islets of Langerhans within the pancreas. It is apparent that inflammation can inhibit the production of serotonin and GABA,  and consequently the drop in GABA and serotonin impairs the body’s ability to regulate inflammation, creating a feed-forward cycle of disorder.

Epinephrine: Along with cortisol, epinephrine has been found in the urine of patients recently exposed to physical and or emotional trauma. It actually has a surprisingly strong anti-oxidant effect, and it regenerates easily. It also has a direct down-regulatory effect on the pro-inflammatory activities of neutrophils. This occurs via enhancement of cAMP-mediated clearance of cytosolic Ca(2+). When elevated, epinephrine is generally associated with recent or short-term trauma.

Dopamine: Inflammation-associated reductions of dopamine and dopamine metabolites in cerebrospinal fluid correlate with symptoms of anhedonia, fatigue, and psychomotor retardation. 

Glutamate: An elevated level of glutamate can be a response to inflammation. For example, in people with major depression, increased inflammation may lead to a surge of glutamate in the basal ganglia in association with glial dysfunction. However, increased glutamate triggered by other sources, can also cause inflammation in the brain. This has implications for the risk of dementia. 

Norepinephrine: This may be the most important of all neurotransmitters in the context of inflammation and inflammation-related diseases. Normal levels of norepinephrine suppress the expression of pro-inflammatory cytokines (TNF, IL-1β) and signalling molecules (iNOS), while increasing the expression of anti-inflammatory cytokines (IL-10) and molecules. Healthy levels of norepinephrine inhibit NF-kB. Chronic inflammation leads to a depletion of norepinephrine, and a lifting of the brake that it normally exerts on NF- kB and other pro-inflammatory signals.  .

So, what is the best clinical method for assessing neurotransmitters?

I believe that measurement of neurotransmitter metabolites in urine, when handled and processed efficiently, is most efficient for clinical use. Urinary neurotransmitters are easily collected. Also, urinary neurotransmitters are stable during collection and transportation, whereas platelets may not be nearly as stable. Further, urinary neurotransmitter intermediaries may best reflect enzyme functions. Urinary levels of neurotransmitters primarily reflect the activity of the peripheral and enteric nervous systems, allowing for measurement of not only brain activity and its role in inflammation, but also the whole body’s inflammatory process.

Simply put, oxidation and inflammation are both mediated by and reflected by the brain, the peripheral, and the central nervous systems. The HPA axis is the key link. Clinically, accurate assessment of inflammation can most easily be obtained via urine test technologies.