Interacting neurotransmitter systems. A non-experimental approach to the 5HIAA-HVA correlation in human CSF

The repeatedly observed strong positive correlation between 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) in human cerebrospinal fluid (CSF) prompted an investigation to see if conclusions concerning possible interactions between brain serotonin and dopamine turnover could be reached from human CSF concentrations of these acid metabolites. CSF data from patients with depressive disorders diagnosed according to the RDC from Sweden (n = 140) and from the National Institute of Mental Health (n = 35) were used to test structural hypotheses by two statistical approaches--LISREL analysis and logistic regression. Results from both men and women were unequivocal: 5HIAA "controls" HVA, interpretable as a regulatory action of serotonin turnover on dopamine turnover. In women, only 5HIAA was affected by age, height and body size (higher in elderly, short and stout women); no similar relationships were seen in males. The concept of a serotonergic regulation of dopamine turnover was tested on brain punch analyses of serotonin and dopamine and their metabolites in two sets of dogs in a large number of brain areas. Results confirm a facilatory effect of serotonin on indices of dopamine turnover in many brain regions, especially brain stem and hypothalamus. The animal data validate the data analytic approach in humans.