5-Hydroxyindoleacetic Acid Levels in the Cerebrospinal Fluid of Depressive Patients treated with Probenecid


ACCORDING to the serotonin (5-hydroxytryptamine, 5-HT) hypothesis there is a causal relationship between mental depression and 5-HT deficiency in the brain1–3. Some depressive patients—mainly those suffering from an endogenous depression—display the following clinical signs. (1) The concentration of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) (refs. 4 and 5) and the urinary concentrations of 5-HT (ref. 6) and 5-HIAA (refs. 7 and 8) are unusually low. (2) The transformation of 5-hydroxytryptophan into 5-HT seems to be defective9 (although in a later publication Coppen1 reported his inability to reproduce these findings). (3) Precursors of 5-HT which readily enter the brain—5-hydroxytryptophan10 and tryptophan11—can have a therapeutic effect. Finally, in suicide victims the cerebral concentration of indoleamines proved to differ from that in a control group and, according to Shaw et al.12, the 5-HT concentrations were diminished. Bourne et al.13 were unable to corroborate this but did find a diminished concentration of 5-HIAA.

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VAN PRAAG, H., KORF, J. & PUITE, J. 5-Hydroxyindoleacetic Acid Levels in the Cerebrospinal Fluid of Depressive Patients treated with Probenecid. Nature 225, 1259–1260 (1970). https://doi.org/10.1038/2251259b0

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