Age and Gender-Related Changes in Biogenic Amine Metabolites in Cerebrospinal Fluid in Children

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 878)


Metabolites of cerebrospinal biogenic amines (dopamine and serotonin) are an important tool in clinical research and diagnosis of children with neurotransmitter disorders. In this article we focused on finding relationships between the concentration of biogenic amine metabolites, age, and gender. We analyzed 148 samples from children with drug resistant seizures of unknown etiology and children with mild stable encephalopathy aged 0–18 years. A normal profile of biogenic amines was found in 107 children and those children were enrolled to the study group. The CSF samples were analyzed by HPLC with an electrochemical detector. The concentrations of the dopamine and serotonin metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), respectively, were high at birth, gradually decreasing afterward until the 18 years of age. Nevertheless, the HVA/5-HIAA ratio did not vary with age, except in the children below 1 year of age. In the youngest group we observed a strong relationship between the HVA/5-HIAA ratio and age (r = 0.69, p < 0.001). There were no statistical differences in the level of both dopamine and serotonin metabolites between boys and girls, although a trend toward lower HVA and 5-HIAA in the boys was noticeable. Significant inter-gender differences in the level of HVA and 5-HIAA were noted only in the age-group of 1–4 years, with 5-HIAA being higher in the girls than boys (p = 0.004). In conclusion, the study revealed that the concentration of biogenic amine metabolites is age and sex dependent.


Biogenic amines Brain metabolism Cerebrospinal fluid Children Gender Neurotransmitters 



The study was supported in part by MNiSW grant N406 030 31/0915.

Conflicts of Interest

The authors declare no conflicts of interest in relation to this article.


  1. Aitkenhead H, Heales SJ (2013) Establishment of pediatric age – related reference intervals for serum prolactin to aid in the diagnosis of neurometabolic conditions affecting dopamine metabolism. Ann Clin Biochem 50(Pt 2):156–158CrossRefPubMedGoogle Scholar
  2. Biver F, Lotstra F, Monclus M, Wikler D, Damhaut P, Mendlewicz J, Goldman S (1996) Sex differences in 5HT2 receptor in the living human brain. Neurosci Lett 204(1–2):25–28CrossRefPubMedGoogle Scholar
  3. Blau N, Thony B, Cotton RG, Hyland K (2001) Disorders of tetrahydrobiopterin and related biogenic amines. In: Scriver CR, Beaduet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, New York, pp 1725–1776Google Scholar
  4. Blau N, Duran M, Blaskovics ME, Gibson KM (2005) Physician’s guide to the laboratory diagnosis of metabolic diseases, 2nd edn. Springer, HeidelbergGoogle Scholar
  5. Dennis RL, Lay DC Jr, Cheng HW (2013) Effects of early serotonin programming on behavior and central monoamine concentrations in an avian model. Behav Brain Res 253:290–296CrossRefPubMedGoogle Scholar
  6. Duarte S, Sanmarti F, Gonzalez V, Perez Duenas B, Ormazabal A, Artuch R, Campistol J, Garcia-Cazorla A (2008) Cerebrospinal fluid pterins and neurotransmitters in early severe epileptic encephalopathies. Brain Dev 30(2):106–111Google Scholar
  7. Goldman-Rakic PS, Brown RM (1982) Postnatal development of monoamine content and synthesis in the cerebral cortex of rhesus monkeys. Dev Brain Res 4:339–349CrossRefGoogle Scholar
  8. Heales SJ (2008) Biogenic amines. In: Blau N, Duran M, Gibson KM (eds) Laboratory guide to the methods in biochemical genetics. Springer, Berlin, pp 703–715CrossRefGoogle Scholar
  9. Hoffmann GF, Sutees RA, Wevers RA (1998) Cerebrospinal fluid investigation for neurometabolic disorders. Neuropediatrics 29:59–71CrossRefPubMedGoogle Scholar
  10. Hyland K (1999) Neurochemistry and defects of biogenic amine neurotransmitter metabolism. J Inherit Metab Dis 22:353–363CrossRefPubMedGoogle Scholar
  11. Hyland K (2006) Cerebrospinal fluid analysis in the diagnosis of treatable inherited disorders of neurotransmitter metabolism. Future Neurol 1(5):593–603CrossRefGoogle Scholar
  12. Hyland K, Surtees RA, Heales SJ, Bowron A, Howells DW, Smith I (1993) Cerebrospinal fluid concentrations of pterins and metabolites of serotonin and dopamine in a pediatric reference population. Pediatr Res 34:10–14CrossRefPubMedGoogle Scholar
  13. Kandel ER, Siegelbaum SA, Schwartz JH (2000) Elementary interactions between neurons: synaptic transmission. In: Kandel ER, Schwartz JH, Jessel TM (eds) Principles of neural science. McGraw-Hill, New York, pp 123–134Google Scholar
  14. Kurian MA, Gissen P, Smith M, Heales SJ, Clayton PT (2011) The monoamine neurotransmitter disorders: an expanding range of neurological syndromes. Neurology 10:721–733PubMedGoogle Scholar
  15. Kusmierska K, Jansen EE, Jakobs C, Szymańska K, Małunowicz E, Meilei D, Thony B, Blau N, Tryfon J, Rokicki D, Pronicka E, Sykut-Cegielska J (2009) Sepiapterin reductase deficiency in a 2-year-old girl with incomplete response to treatment during short-term follow-up. J Inherit Metab Dis 32(Suppl 1):S5–S10CrossRefPubMedGoogle Scholar
  16. Maciag D, Simpson KL, Coppinger D, Lu Y, Wang Y, Lin RC, Paul AI (2006) Neonatal antidepressant exposure has lasting effects on behavior and serotonin circuitry. Neuropsychopharmacology 31:47–57PubMedCentralPubMedGoogle Scholar
  17. Montoya ER, Terburg D, Bos PA, van Honk J (2012) Testosterone, cortisol, and serotonin as key regulators of social aggression: a review and theoretical perspective. Motiv Emot 36:65–73PubMedCentralCrossRefPubMedGoogle Scholar
  18. Ormazabal A, Artuch R, Vilaseca MA, Aracil A, Pineda M (2005) Cerebrospinal fluid concentration of folate, biogenic amines and pterins in Rett syndrome: treatment with folinic acid. Neuropediatrics 5:380–385CrossRefGoogle Scholar
  19. Pearl PL, Hartka TR, Taylor J (2006) Diagnosis and treatment of neurotransmitter disorders. Curr Treat Options Neurol 8:441–450CrossRefPubMedGoogle Scholar
  20. Smith KM, Dahodwala N (2014) Sex differences in Parkinson’s disease and other movement disorders. Exp Neurol 259:44–56CrossRefPubMedGoogle Scholar
  21. Thomson BL, Stanwood GD (2009) Pleiotropic effects of neurotransmission during development: modulators of modularity. J Autism Dev Disord 39:260–268CrossRefGoogle Scholar
  22. Van Der Heyden JC, Rotteveel JJ, Wevers RA (2003) Decreased homovanillic acid concentrations in cerebrospinal fluid in children without a known defect in dopamine metabolism. Eur J Paediatr Neurol 7:31–37CrossRefGoogle Scholar
  23. Van Goozen SH, Fairchild G (2006) Neuroendocrine and neurotransmitter correlates in children with antisocial behavior. Horm Behav 50:647–654CrossRefPubMedGoogle Scholar
  24. Verbeek MM, Blom AM, Wevers RA, Lagerwerf AJ, Van de Geer J, Willemsen MA (2008) Technical and biochemical factors affecting cerebrospinal fluid 5-MTHF, biopterin and neopterin concentrations. Mol Genet Metab 95:127–132CrossRefPubMedGoogle Scholar
  25. Whitaker-Azmitia PM (2005) Behavioral and cellular consequences of increasing serotonergic activity during brain development: a role in autism. Int J Dev Neurosci 23:75–83CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Newborn Screening LaboratoryInstitute of Mother and ChildWarsawPoland
  2. 2.Department of Experimental and Clinical NeuropathologyMedical Research Center, Polish Academy of SciencesWarsawPoland
  3. 3.Department of Child PsychiatryMedical University of WarsawWarsawPoland
  4. 4.Department of Pediatrics, Nutrition and Metabolic DiseasesThe Children Memorial InstituteWarsawPoland
  5. 5.Department of Neurology and EpileptologyThe Children Memorial InstituteWarsawPoland
  6. 6.Clinic of Child and Adolescent NeurologyInstitute of Mother and ChildWarsawPoland
  7. 7.Department of Medical GeneticsThe Children Memorial InstituteWarsawPoland
  8. 8.Department of Laboratory Diagnostics and Clinical Immunology of Developmental AgeMedical University of WarsawWarsawPoland

Personalised recommendations