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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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    Coppen, A., Brit. J. Psychiat., 113, 1237 (1967).

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    Lapin, T. P., and Oxenbrug, G. F., Lancet, i, 132 (1969).

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    van Praag, H. M., Pharmakopsychiat. Neuropsychopharmak., 3, 151 (1969).

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    Coppen, A., Shaw, D. M., and Malleson, A. J., Brit. J. Psychiat., 111, 105 (1965).

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    Coppen, A., Shaw, D. M., Herzberg, B., and Maggs, R., Lancet, ii, 1178 (1967).

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    Shaw, D. M., Camps, F. E., and Eccleston, E. C., Brit. J. Psychiat., 113, 1407 (1967).

  13. 13

    Bourne, H. R., Bunney, W. E., Colburn, R. W., Davis, J. M., Davis, J. N., Shaw, D. M., and Coppen, A. J., Lancet, ii, 805 (1968).

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    Neff, N. H., Tozer, T. N., and Brodie, B. B., J. Pharmacol., 158, 214 (1967).

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    van Praag, H. M., Brit. J. Psychiat., 114, 1195 (1968).

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