Cerebrospinal Fluid Amine Metabolites in Affective Illness: The Probenecid Technique

Probenecid inhibits the removal of 5-HIAA and HVA (the major metabolites of serotonin and dopamine) from the cerebrospinal fluid. The accumulation of these metabolites following high doses of probenecid was studied in patients with affective illness in order to assess central amine function. The metabolite accumulation was increased by administering the appropriate precursors (which increase amine synthesis) and was decreased by administering specific synthesis inhibitors. Compared with controls, the depressed patients had low HVA accumulation, while addicts on methadone had low 5-HIAA accumulation. Within the group of depressed patients, HVA accumulation was higher in bipolar than in unipolar patients.