Matt Pratt-Hyatt, CSO

As a practitioner, you are likely well versed in assessing and understanding symptomatic presentation in your patients. But have you ever considered testing their urine for subtle signals about their mental health?

It might sound far-fetched, but the latest science suggests there is a powerful connection between the brain and urine. This blog explores this; covering what neurotransmitters are, what they do, the latest research on their transportation around the body, and which specific metabolites found in urine can offer valuable clues into your patients’ mental wellbeing.

The Lowdown on Neurotransmitters
Neurotransmitters are the most common way in which the nervous system relays messages. These small molecules are released by neurons and dock with receptors on other neurons. Found throughout the body, they are present in serum, plasma, cerebral spinal fluid, and urine.

As well as playing a critical role in message transmission throughout the nervous system, neurotransmitters also play key roles in endocrinological and immunological activities (1).

From the Brain to the Urine
Because of the blood-brain barrier (BBB) there has been a reluctance to believe that neurotransmitters in the urine have any correlation with the amounts in the brain and central nervous system (CNS).

However, newer research shows several active transport systems that undertake bidirectional movement of neurotransmitters across the BBB. These include the serotonin transporter (SERT), norepinephrine transporter (NET), GABA transporter (GAT) and the excitatory amino acid transporter (EAAT) (2, 3).

Studies have shown correlations between the CNS and urine neurotransmitters and sometimes, radiolabelled neurotransmitters inserted in the brain ending up in the urine (4-6).

More importantly there have been multiple studies that correlate neurotransmitters in urine with multiple neurological conditions. Studies have found utility in urine studies for stress (7), bipolar depression (8), major depressive disorder (9, 10), anxiety (11), and ADHD (12).

Here at KBMO Molecular Diagnostics, we have worked to find the most correlated markers for neurotransmitters. These are the ones that we have found to be the most helpful:

Relevance in Clinical Practice
Whilst the idea of assessing neurotransmitter health through urine might once have been dismissed, emerging science validates its relevance. Understanding and testing for key metabolites offers a non-invasive window into your patients’ brain chemistry and may help you guide more personalised, functional approaches to their neurological health.

Want to Learn More?
If you’re interested in learning more about how neurotransmitters in urine can provide insights into neurological health, stress, and mood disorders, please contact us here.

The KBMO Diagnostics Metabolics Insights Profile (MIP) provides a full metabolic snapshot for your patients, including markers that can reveal issues such as nutritional deficiencies, microbial overgrowth, toxic exposure, oxalates, mitochondrial impairment, neurotransmitter imbalances and other important insights.

References:

1. D. T. Marc, J. W. Ailts, D. C. Campeau, M. J. Bull, K. L. Olson, Neurotransmitters excreted in the urine as biomarkers of nervous system activity: validity and clinical applicability. Neurosci Biobehav Rev 35, 635-644 (2011).
2. R. A. Hawkins, R. L. O’Kane, I. A. Simpson, J. R. Vina, Structure of the blood-brain barrier and its role in the transport of amino acids. J Nutr 136, 218S-226S (2006).
3. Y. Nakatani et al., Augmented brain 5-HT crosses the blood-brain barrier through the 5-HT transporter in rat. Eur J Neurosci 27, 2466-2472 (2008).
4. C. P. Lynn-Bullock, K. Welshhans, S. L. Pallas, P. S. Katz, The effect of oral 5-HTP administration on 5-HTP and 5-HT immunoreactivity in monoaminergic brain regions of rats. J Chem Neuroanat 27, 129-138 (2004).
5. M. Gallowitsch-Puerta, V. A. Pavlov, Neuro-immune interactions via the cholinergic anti-inflammatory pathway. Life Sci 80, 2325-2329 (2007).
6. A. Roy, S. Pollack, Are cerebrospinal fluid or urinary monoamine metabolite measures stronger correlates of suicidal behavior in depression? Neuropsychobiology 29, 164-167 (1994).
7. K. Tanabe, A. Yokota, Mental stress objective screening for workers using urinary neurotransmitters. PLoS One 18, e0287613 (2023).
8. S. H. Koslow et al., CSF and urinary biogenic amines and metabolites in depression and mania. A controlled, univariate analysis. Arch Gen Psychiatry 40, 999-1010 (1983).
9. B. S. Gadad et al., Peripheral biomarkers of major depression and antidepressant treatment response: Current knowledge and future outlooks. J Affect Disord 233, 3-14 (2018).
10. P. Zheng et al., Identification of sex-specific urinary biomarkers for major depressive disorder by combined application of NMR- and GC-MS-based metabonomics. Transl Psychiatry 6, e955 (2016).
11. L. K. Homandberg, T. E. Fuller-Rowell, Experiences of Discrimination and Urinary Catecholamine Concentrations: Longitudinal Associations in a College Student Sample. Ann Behav Med 54, 843-852 (2020).
12. A. Kusaga et al., Increased urine phenylethylamine after methylphenidate treatment in children with ADHD. Ann Neurol 52, 372-374 (2002).
13. D. F. Davidson, Elevated urinary dopamine in adults and children. Ann Clin Biochem 42, 200-207 (2005).
14. M. Matsuo, R. Tasaki, H. Kodama, Y. Hamasaki, Screening for Menkes disease using the urine HVA/VMA ratio. J Inherit Metab Dis 28, 89-93 (2005).
15. J. R. Lenchner, C. Santos, “Biochemistry, 5 Hydroxyindoleacetic Acid” in StatPearls. (Treasure Island (FL), 2025).