5-Hydroxyindolacetic acid and homovanillic acid in cerebrospinal fluid in manic-depressive psychosis

Abstract

Cerebrospinal fluid concentrations of 5-hydroxyindoleacetic acid and homovanillic acid were determined in 37 depressed and 47 manic patients, in 30 other psychiatric patients and in 54 healthy controls. There were no differences in the concentrations of 5-hydroxyindoleacetic acid between the four groups. Manic patients had higher concentrations of homovanillic acid than the other three groups. After loading with probenecid (5 g during 50 h), which blocks the outflow of acid metabolites of monoamines from cerebrospinal fluid, the increase in 5-hydroxyindoleacetic acid levels at a second lumbar puncture was significantly smaller in the manic-depressive patients (about 20%) than in the other two groups (about 60%). The rise in the concentration of homovanillic acid was smaller in manic depressive patients (about 80%) than in the two control groups (about 200%). In a further experiment, methylperidol, a neuroleptic compound which increases the turnover rate of brain dopamine, was administered with probenecid in an attempt to accentuate the differences between the groups. Methylperidol increased the differences between the manic-depressives and the controls for homovanillic acid, and removed the differences for 5-hydroxyindoleacetic acid. These findings indicate a lower turnover rate of dopamine and 5-hydroxytryptamine in both phases of manic-depressive psychosis. — In the probenecid experiments, bipolar depressive patients had lower increases of 5-hydroxyindole acetic acid than cases of unipolar endogenous depression. Treatment with lithium, tricyclic antidepressants and various neuroleptics did not affect the concentrations of 5-hydroxyindoleacetic acid and homovanillic acid. The concentrations of these compounds in cerebrospinal fluid in subjects not premedicated at the second lumbar puncture were relatively unchanged when measured on two occasions at different time intervals.