Introduction: The amino acids that function as co-agonists at the N-methyl-D-aspartate (NMDA)
receptor have been investigated in bipolar disorder (BD). However, studies comparing amino acid
levels in the plasma of BD patients with healthy controls have yielded inconsistent results. We,
therefore, conducted a study in Hospital Universiti Sains Malaysia to determine the plasma levels
of glutamate, glycine, and alanine in BD patients and compared them with the healthy controls.
Materials and Methods: An overnight fast of 10-hour plasma levels of glutamate, glycine, alanine,
and tryptophan were measured in 83 bipolar patients, and were compared to a group of 82 healthy
controls. Results: The mean (SD) age of bipolar patients was 40.9 (12.1), while the mean (SD) age
for control groups was 35.6 (7.7) years. The median (25th, 75th percentile) of glutamate and alanine
levels in bipolar patients was 111.0 (65.0,176.0) and 530.0 (446.0,629.0), respectively, while the
mean (SD) of glycine level in bipolar patients was 304.0 (98.1). Significant higher glutamate, glycine,
and alanine levels were found in bipolar disorder patients in the manic episode as compared to the
healthy controls. Conclusion: Although the exact relationship between peripheral NMDA receptor
co-agonist levels in the pathogenesis of BD is not well understood, these findings should be explored
and may enlighten some new paths for BD therapy which could reward the patients also clinicians.