Glutamate-hypothalamic-pituitary-adrenal axis interactions: Implications for mood and anxiety disorders

Sanjay J. Mathew, Jeremy D. Coplan, Eric L.P. Smith, Darryle D. Schoepp, Leonard A. Rosenblum, Jack M. Gorman

Research output: Contribution to journalReview articlepeer-review

42 Scopus citations


Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a pathologic feature of certain mood and anxiety disorders that results in the increased production and secretion of corticotropin-releasing factor. There is increasing preclinical evidence that glutamate, an excitatory amino acid, plays an important role in the regulation of the HPA axis. Activation of glutamatergic projections to limbic structures such as the amygdala and brainstem structures such as the nucleus tractus solitarius is implicated in the stress response. There are laboratory and clinical suggestions that glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonists function as antidepressants, and that chronic antidepressant treatments have a significant impact on NMDA receptor function. Clinical investigations of glutamate antagonists in patients with mood and anxiety disorders are in their infancy, with a few reports suggesting the presence of mood-elevating properties. Ultimately, HPA axis modulators, serotonin-enhancing agents, and glutamate antagonists might serve to increase neurotropic factors in key brain regions for affective and anxiety regulation, providing a putative final common pathway.

Original languageEnglish
Pages (from-to)555-564
Number of pages10
JournalCNS Spectrums
Issue number7
StatePublished - 2001
Externally publishedYes


Dive into the research topics of 'Glutamate-hypothalamic-pituitary-adrenal axis interactions: Implications for mood and anxiety disorders'. Together they form a unique fingerprint.

Cite this