The International Journal of Neuropsychopharmacology

Plasma glycine and serine levels in schizophrenia compared to normal controls and major depression: relation to negative symptoms

Tomiki Sumiyoshi a1a2, A. Elif Anil a1a3, Dai Jin a1, Karu Jayathilake a1, Myung Lee a1 and Herbert Y. Meltzer a1c1
a1 Department of Psychiatry, Division of Psychopharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA
a2 Department of Neuropsychiatry, Toyama Medical and Pharmaceutical University, Toyama, Japan
a3 Department of Psychiatry, Hacettepe University Faculty of Medicine, Ankara, Turkey

Article author query
sumiyoshi t   [PubMed][Google Scholar] 
anil a   [PubMed][Google Scholar] 
jin d   [PubMed][Google Scholar] 
jayathilake k   [PubMed][Google Scholar] 
lee m   [PubMed][Google Scholar] 
meltzer h   [PubMed][Google Scholar] 


Previous studies have suggested decreased N-methyl-D-aspartate (NMDA)-type glutamate receptor function may contribute to increased negative symptoms in patients with schizophrenia. Consistent with this hypothesis, glycine, a co-agonist at NMDA receptors, has been reported to improve negative symptoms associated with the illness. This study was performed to determine if plasma levels of glycine or its ratio to serine, a precursor of glycine, are decreased in patients with schizophrenia compared to normal control subjects or patients with major depression. We also tested the hypothesis that these amino acids were correlated with negative symptoms in subjects with schizophrenia. Plasma levels of glycine, serine, and their ratio, were compared in 144 patients with schizophrenia, 44 patients with major depression, and 49 normal control subjects. All subjects were medication-free. Psychopathology was evaluated using the Brief Psychiatric Rating Scale (BPRS). Plasma glycine levels and glycine/serine ratios were decreased in patients with schizophrenia relative to control subjects and patients with major depression. By contrast, serine levels were increased in patients with schizophrenia compared to normal subjects but not compared to major depression. Patients with major depression also had increased plasma serine levels and decreased glycine/serine ratios compared to normal controls, but glycine levels were not different from those of normal controls. In subjects with schizophrenia, glycine levels predicted the Withdrawal–Retardation score (BPRS), whereas no such correlation was found in subjects with major depression. These results provide additional evidence that decreased availability of glycine may be related to the pathophysiology of negative symptoms. The decreases in plasma glycine levels support the evidence for an abnormality in the glutamatergic system in schizophrenia, and provide additional support for efforts to improve negative symptoms by augmentation of antipsychotic drugs with agonists at the glycine site of the NMDA receptor.

(Received January 8 2003)
(Reviewed March 9 2003)
(Revised May 11 2003)
(Accepted May 18 2003)

Key Words: Amino acids; glycine; glutamate; negative symptoms; NMDA; schizophrenia; serine.

c1 Dr. H. Y. Meltzer, Department of Psychiatry, Vanderbilt University School of Medicine, Psychiatric Hospital at Vanderbilt, 1601 23rd Avenue South, Suite 306, Nashville, TN 37212, USA. Tel.: +1-615-327-7049 Fax: +1-615-327-7093 E-mail: