The validity of urinary neurotransmitter measurements.
By Gottfried Kellermann, PhD
Many diseases are associated with specific chemical alterations; these alterations are commonly called biomarkers and are routinely used to determine if a medical event or process will occur, is occurring, or has occurred. While they may be indirect, the interest in identifying chemical measurements that can be used as biomarkers is very high. This is especially true for conditions that currently do not have diagnostic biomarkers, such as mood and hyperactivity disorders. Chemicals like neurotransmitters, which change in a predictable manner and parallel the patient's clinical symptoms, have become valuable markers for medical processes within the body. (1)
There are a number of body fluids in which neurotransmitters can be assessed, each associated with various advantages and disadvantages. Common measurements include:
CSF measurements represent central nervous system (CNS) neurotransmitter levels. While this type of assessment may provide the best representation of what is happening in the CNS, it carries significant drawbacks. Sample collection (spinal tap) is highly invasive, which not only creates an inconvenience for the patient, the stress involved also influences the levels of key neurotransmitters including epinephrine and norepinephrine. Secondly, optimal ranges for the various neurotransmitters have not been established for CSF measurements, thus making results difficult to interpret.
Similarly, blood measurements carry many of the same invasive drawbacks that CSF measurements do. As with a spinal tap, the stress associated with venipuncture significantly influences the levels of epinephrine and norepineprhine. Blood collections require specific storage and transportation measures in order to preserve sample integrity.
The value of testing urinary neurotransmitters as a non-invasive way to assess a person's health has a long medical history and is becoming an increasingly popular method of assessing health. Urinary neurotransmitter testing is frequently used as a marker for pheochromocytoma. (2) Neurotransmitter testing is also being used in the assessment of many psychological disorders. Part of the increase in popularity is due to the creation of optimal ranges, developed by NeuroScience, that allow for useful interpretation of the results. A review of the current scientific literature reveals four areas in clinical practice where urinary neurotransmitter testing may be of value:
Neurotransmitters & Disease
Knowledge regarding the value of urine neurotransmitter testing is growing rapidly and it is well established that there are relationships between a patient's mental health and their urine neurotransmitter levels. For example, studies have shown that many patients with depression have low urinary serotonin and dopamine and elevated norepinephrine levels. (1,3) Likewise, medical studies have reported that patients with Post-Traumatic Stress Disorder (PTSD) frequently have elevated urinary catecholamines (epinephrine, norepinephrine, and dopamine). (4,5) While some of these findings may be suggestive of a role of neurotransmitters in the diseases studied, the existence of causal relationship cannot be definitively made. However, since researchers have repeatedly demonstrated that urinary neurotransmitter measurements correlate with neurological conditions, it suggests that urinary neurotransmitter testing is a valuable tool in patient assessment. These biological measures may also provide insight regarding the disease's underlying physiological mechanisms.
Guiding Treatment Selection
Not only can urinary measurements identify imbalances associated with a particular condition, they can also establish the need for intervention and guide the practitioner in selecting the best-suited therapeutic approach. For example, two popular choices for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) include Strattera and Ritalin. Numerous literature sources suggest the ability to focus/concentrate is linked to at least three key neurotransmitters, norepinephrine, epinephrine, and phenylethylamine (PEA). (6,7) As a selective norepinephrine reuptake inhibitory, Strattera primarily affects norepinephrine and epinephrine levels. As a stimulant, Ritalin affects PEA levels. Choosing the proper drug will enhance the clinical outcome and when deciding which approach is best for a particular patient, a neurotransmitter test that includes norepinephrine, epinephrine, and PEA levels can provide useful insight.
Monitoring Treatment Effectiveness
While urinary neurotransmitter analysis is a useful tool to differentiate between the healthy and unwell populations, it can also be utilized to monitor the effectiveness of treatment regimens in patients with neurological disorders. In depressed patients treated with 5-hydroxytryptophan (5-HTP), those with greater increases in urinary serotonin had better clinical response than patients who had a lesser increase in their urinary serotonin. (8) This suggests that urine serotonin levels correlate with the clinical response to oral 5-HTP.
Although urinary neurotransmitter testing has extraordinary value in helping to identify the underlying neurochemicals that affect mental disorders, guide selection of appropriate treatment strategies, and monitor treatment regimens, the power in urine neurotransmitter testing may lie in the ability to help prevent the manifestation of mental disorders. For example, urinary epinephrine levels after a traumatic event may be associated with an increased risk of developing PTSD. (5) Changes in urinary serotonin, dopamine, and glutamate levels have also been suggested as markers for neurobehavioral toxicology caused by environmental pollutants such as fossil fuels and heavy metals. (9,10) Urinary neurotransmitter evaluations of this type may be of predictive value in determining when a psychiatric disorder is more likely to occur and as such may indicate when more careful observation or preventive strategies may be implemented prior to the development of the disease.
Central Nervous System vs. Urinary Neurotransmitter Levels
A recent study in rats supports the link between increased urine serotonin and an improved clinical response by finding parallel increases in brain slice, plasma, and urine serotonin levels after dosing with oral 5-HTP. (11) The link between factors in the urine and the brain is also seen when the effectiveness of mental stimulants like methylphenidate and dextroamphetamine can be predicted by the degree to which phenylethylamine (PEA) increases in urine. (7) In addition, therapies used to treat depression have been found to reduce the elevated urinary norepinephrine levels in depressed patients. (12) This evidence suggests that urinary neurotransmitter levels correlate well with many psychiatric conditions.
Psychiatric disorders like depression or anxiety may be diagnosed based only on clinical signs and symptoms, but identifying imbalances in brain chemicals that are associated with the presence of the disorder can provide insights regarding possible prevention and treatment strategies that are not evident in the diagnosis alone. As the number of urinary neurotransmitters tested grows, the predictive value of neurotransmitter test panels will become more powerful and the ability to prevent disorders, improve treatment through early detection, and/or match or monitor treatments to the patient's condition, will improve.
Gottfried Kellermann, PhD
Osceola, Wisconsin 54020 USA
1. Hughes JW, Watkins L, Blumenthal JA, Kuhn C, Sherwood A. Depression and anxiety symptoms are related to increased 24-hour urinary norepinephrine excretion among healthy middle-aged women. J Psychosom Res. 2004 Oct;57(4):353-8.
2. Duncan MW, Compton P, Lazarus L, Smythe GA. Measurement of norepinephrine and 3,4-dihydroxyphenylglycol in urine and plasma for the diagnosis of pheochromocytoma. N Engl J Med. 1988 Jul 21;319(3):136-42.
3. Hernandez-Reif M, Ironson G, Field T, Hurley J, Katz G, Diego M, Weiss S, Fletcher MA, Schanberg S, Kuhn C, Burman I. Breast cancer patients have improved immune and neuroendocrine functions following massage therapy. J Psychosom Res. 2004 Jul;57(1):45-52.
4. Yehuda R, Southwick S, Giller EL, Ma X, Mason JW. Urinary catecholamine excretion and severity of PTSD symptoms in Vietnam combat veterans. J Nerv Ment Dis. 1992 May;180(5):321-5.
5. Delahanty DL, Nugent NR, Christopher NC, Walsh M. Initial urinary epinephrine and cortisol levels predict acute PTSD symptoms in child trauma victims. Psychoneuroendocrinology. 2005 Feb;30(2):121-8.
6. Purper-Ouakil D, Fourneret P, Wohl M, Reneric JP. Atomoxetine: a new treatment for Attention Deficit/Hyperactivity Disorder (ADHD) in children and adolescents. Encephale. 2005 May-Jun;31(3):337-48.
7. Kusaga A, Yamashita Y, Koeda T, Hiratani M, Kaneko M, Yamada S, Matsuishi T. Increased urine phenylethylamine after methylphenidate treatment in children with ADHD. Ann Neurol. 2002 Sep;52(3):372-4.
8. Takahashi S, Takahashi R, Masumura I, Miike A. Measurement of 5-hydroxyindole compounds during L-5-HTP treatment in depressed patients. Folia Psychiatr Neurol Jpn. 1976;30(4):461-73.
9. The Development of Neurobehavioral Toxicology in China: The 1994 Hanninen Lecture. Authors: Liang Y.X.; Chen Z.Q.; Wang C.; Tang H.W.; Yang H.G. Environmental Research, Volume 73, Number 1-2, April 1997, pp. 9-17(9)
10. Comparative Neurobehavioral Toxicity Assessment of Three Hydrocarbon Fuels. Authors: Alan F. Nordholm; Naval Medical Research Inst Toxicology Detachment Wright-Patterson AFB OH Pages: 83 Report Date: Aug 1998 Report number: A754863
11. Lynn-Bullock CP, Welshhans K, Pallas SL, Katz PS. The effect of oral 5-HTP administration on 5-HTP and 5-HT immunoreactivity in monoaminergic brain regions of rats. J Chem Neuroanat. 2004 May;27(2):129-38.
12. Linnoila M, Karoum F, Rosenthal N, Potter WZ. Electroconvulsive treatment and lithium carbonate. Their effects on norepinephrine metabolism in patients with primary, major depressions. Arch Gen Psychiatry. 1983 Jun;40(6):677-80.
Reprinted with permission from NeuroScience, Inc