Clinical Chemistry, Vol 7, 203-230, Copyright © 1961 by the American Association for Clinical Chemistry

Indole Metabolism in Mental Illness

¹ Laboratory of Research Biochemistry, Veterans Administration Hospital, Coatesville, Pa., and the Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pa.

Abnormal indole metabolism, long implicated in mental illness, is well delineated in three diseases having mental symptoms: phenylketonuria, Hartnup (H or Hart's) disease, and pellagra. Recent research suggests that indole metabolism may be disturbed in schizophrenia. The evidence for this is evaluated in terms of: number and effectiveness of indolic psychotogens, effect of indoles on the brain, effect of psychotherapeutic drugs on model psychoses induced by indoles, excretion of urinary indoles before and after tryptophan load tests, animal toxicity tests, urinary glyoxylic acid test, and detection by paper chromatography of abnormal urinary indole production.

The indoles reported in human urine are discussed critically with respect to excretion data, metabolic origin, and possible relationship to mental disease. Urinary excretion studies in mental illness must consider such factors as medication, dietary differences, excretion products from intestinal bacteria, eccentric bowel habits, age, muscle mass, sex, physical activity, and adequate normal controls. In various reports, these factors were not well controlled. In some carefully conducted studies, however, abnormal excretion was still detected in schizophrenics, particularly in studies dealing with the glyoxylic acid test and 6-hydroxyskatole sulfate excretion. Despite the controversial aspects, reports of abnormal indole metabolism in mental illness are sufficiently numerous to warrant further studies along the lines indicated above.