Monoamine metabolite turnover

The earliest studies to investigate the actions of tricyclic antidepressants highlighted their actions on the turnover of the monoamine metabolites in animal brain. The 'monoamine theory of depression' proposed the reduced functioning of monoamine transmission in depression. Therefore it was natural to seek relevant measures of monoamine chemistry in the cerebrospinal fluid of patients and controls. The study of what became irreverently known as 'neural urine' and indeed of urine itself, since peripheral measures of monoamine turnover are also potentially relevant, virtually defined a decade of biological psychiatry in the 1970s and 1980s. Drugs had similar effects on neurotransmitter turnover as seen in animal studies, demonstrating that the human techniques were sufficiently sensitive. Indeed the monoamine theory is, at its best, a theory about drug action because the monoamine and metabolite changes produced by illness in patients have proved remarkably unconvincing.4,' Typical results are summarized in Table,..! from the largest published samples. The findings for the noradrenaline metabolite MHPG and the 5-HT metabolite 5-hydroxyindoleacetic acid were negative. The dopamine metabolite homovanillic acid did show the predicted decrease, but only significantly in women. There were trends to modest increases in all the major metabolites in mania. Although disappointing, cerebrospinal fluid studies could never reflect the activities of smaller groups of neurones localized in areas critical for the modulation of mood. Such a focus is only possible in isotope imaging (PET or SPET) or better postmortem studies of the brain.

Table 1 Baseline means of monoamine metabolites in cerebrospinal fluid by sex

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