Survey of NMDA Receptor-related Biomarkers for Depression

Abstract

Major depressive disorder (MDD) is an important cause of disability in the world. Depression has negative influences on a person’s mental and physical health, quality of life, and functioning. The pathophysiology of depression has not yet been confirmed. The traditional monoamine hypothesis of MDD could not explain the unsatisfactory treatment response of antidepressants. Thus, it is necessary to search other probable pathophysiology of MDD. In recent years, the role of glutamate neurotransmission in depression has drawn much attention. The N-methyl-D-aspartate receptor (NMDAR) is a subclass of glutamate receptors and is implicated in the pathogenesis of MDD and other mental disorders. Furthermore, NMDAR ligands, such as ketamine and Dcycloserine, have shown antidepressive effects in several studies. The diagnosis of MDD depends on physician’s subjective evaluation which is often inconsistent. Therefore, reliable objective laboratory biomarkers are essential for more accurate and consistent diagnosis of MDD. In this review, we firstly described the structure and regulation of the NMDAR. We then searched different genes involved in the pathway of glutamatergic neurotransmission and NMDAR, including D-amino acids, glycine, and glutamate. Various related enzymes and transporters that play a role in the modulation of NMDAR neurotransmission were also surveyed. This review aims to investigate NMDAR related metabolism, which may serve as feasible indicators for MDD and may contribute to further exploration of reliable biomarkers for MDD and promote new treatment of depression.