HPLC and gas chromatography-mass spectrometry analyses of 18
amino acids,
N-acetylaspartate,
N-acetylaspartylglutamate, and 5-hydroxyindoleacetic
acid, derived from
serotonin, and
homovanillic acid, derived from
dopamine, were performed in CSF collected from a group of patients with
schizophrenia who either had been
drug free for at least 1 year (n = 5) or were
drug naive for
psychotropic drugs (n = 21) and in 15 control subjects. Significant differences were found only for
taurine (15% lower in the patients) and
isoleucine (7% higher). A number of unidentified substances were detected, one of which proved to be markedly reduced (16%) among the schizophrenic patients. Liquid chromatography-mass spectrometry with continuous flow-fast atom bombardment interface allowed us to identify this substance as
gamma-glutamylglutamine. The decreased level of
gamma-glutamylglutamine may reflect a deficiency in the
gamma-glutamyltransferase system, a system probably involved in
glutamate uptake, or a deficiency in
glutamine, an important precursor of releasable
glutamate. Although
glutamate was nonsignificantly reduced in the patients, it was one of the five substances (including
gamma-glutamylglutamine) that were necessary for the best discrimination between the schizophrenic patients and the controls. These findings support the notion that the glutamatergic system is affected in
schizophrenic disorders. In addition, they underscore the need to apply rigid bioanalytical techniques and use
drug-naive patients to gain in-depth information on the pathophysiology of
brain disorders such as
schizophrenia.