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

Abstract

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.

Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia

“…The possibilities include reduction in the concentrations of the co-agonists, glycine [38,39] and D-serine levels [40], elevated levels of endogenous antagonists (NAAG/kynurenic acid) [41,42], alterations in the redox state of the NMDA channel [43] or reduced channel expression or trafficking [13,44].…”

Avaliação de neuropeptídeos e aminoácidos para elucidação da neurobiologia das doenças psiquiátricas

“…Portanto, trata-se de aminoácidos que merecem atenção na pesquisa da esquizofrenia. Enquanto a glicina atua melhorando a ativação dos canais de cátions voltagem dependente do receptor NMDA, achados histoquímicos sugerem que a D-serina pode modular as posições de glicina no receptor NMDA (SUMIYOSHI et al, 2004).…”

“…A glicina é produzida através da serina que está sujeita a ação da enzima serina hidroximetil tranferase (SHMT) e do sistema de clivagem enzimática da glicina (GCS), sendo que a enzima SHMT tem apresentado atividade deficitária em alguns esquizofrênicos (SUMIYOSHI et al, 2004).…”

“…Assim como a queda de glicina sérica reforça a hipótese hipoglutamatérgica da esquizofrenia, ou seja, níveis de glicina mais baixos que os normais estariam relacionados com sintomas negativos. Tais achados sugerem que a glicina poderia servir como marcador periférico da esquizofrenia (SUMIYOSHI et al, 2004).…”

“…Entretanto, a prevalência ao longo da vida chega a 20% (TENG; HUMES; DEMETRIO, 2005 Sendo a glicina produzida a partir da serina que está sujeita a ação da enzima SHMT, serina hidroximetil tranferase, e do GCS, sistema de clivagem enzimática da glicina (SUMIYOSHI et al, 2004), pode-se inferir que estando aumentos os níveis de serina a glicina plasmática conseqüentemente também estará.…”