Published online Jul 19, 2021. doi: 10.5498/wjp.v11.i7.297
Peer-review started: March 7, 2021
First decision: March 30, 2021
Revised: April 13, 2021
Accepted: May 10, 2021
Article in press: May 10, 2021
Published online: July 19, 2021
Core Tip: The versatility of glutamate as the brain’s foremost excitatory neurotransmitter, and modulator of intermediary metabolism in the gastrointestinal tract is considered common knowledge. Years of research suggest glutamate has a role to play in depression. Also, there is increasing evidence of a possible relationship between glutamate and the pathophysiology and/or treatment of depression. The complexity of depression suggests dysregulation of glutamate in sites such as the gastrointestinal tract and brain. The communication link involving dietary glutamate, the gut, endogenous glutamate, and the brain is a multidirectional pathway; the understanding of which is necessary to fully account for glutamate’s role in depression.