Efficacy of High-Dose Glycine in the Treatment of Enduring Negative Symptoms of Schizophrenia

Abstract

DEFICITS IN glutamatergic functioning,^1-9 particularly involving neurotransmission atN-methyl-D-aspartate (NMDA)–type glutamate receptors,^10-13 are postulated to play a key role in the pathophysiology of schizophrenia. The NMDA receptors are stimulated not only by glutamate but also by glycine, an amino acid that acts as an obligatory coagonist at the strychnine-insensitive glycine modulatory site of the NMDA receptor.^14,15 The ability of glycine to potentiate NMDA receptor–mediated neurotransmission, along with the fact that it is well tolerated during both acute and long-term administation, has raised the possibility that it may serve as an effective treatment for neuroleptic-resistant negative symptoms in schizophrenia. The normal diet contains approximately 2 g of glycine per day. Dietary glycine does not normally influence brain glycine levels.¹⁶ When administered in sufficient quantity, however, peripherally administered glycine may pass the blood-brain barrier and functionally elevate brain glycine levels.^17-21