Continuous covariability of dopamine and serotonin metabolites in human cerebrospinal fluid

Background: Experiments in lower animals and humans have demonstrated the existence of functional interactions between serotonin and dopamine in neuronal tissue. However, the relationship between parameters of serotonin and dopamine neuronal activity over time within the central nervous system (CNS) of the individual human has not yet been established. Methods: We used continuous cerebrospinal fluid (CSF) sampling over 6 hours to test the hypothesis that the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the dopamine metabolite homovanillic acid (HVA) significantly covary in concentration over time. Two groups of normal volunteers (total n = 16) were studied at separate hospitals and CSF was assayed for 5-HIAA and HVA by high-performance liquid chromatography (HPLC). Three subjects underwent repeat CSF-withdrawal procedures after a 6-week interval. Results: Strong and sustained positive covariability in concentrations of HVA and 5-HIAA was observed in the CSF of individual humans. High intraindividual correlation coefficients were routinely observed; the mean intraindividual correlation coefficients were +0.897 and +0.871 in the two normal volunteer groups. The HVA to 5-HIAA concentration ratio in CSF was 2.2 ± 0.7 with very little variability over intervals ranging from minutes to weeks. Conclusions: The balance between CSF dopamine and serotonin metabolite concentrations remains relatively constant over time in healthy humans. Serial measures of CSF dopamine and serotonin metabolites within the same person could be an effective model in which to explore the interrelationships between these systems in various psychiatric syndromes, in response to drug treatment, and during provocative testing.