PMID- 37424412
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230901
IS  - 1738-1088 (Print)
IS  - 2093-4327 (Electronic)
IS  - 1738-1088 (Linking)
VI  - 21
IP  - 3
DP  - 2023 Aug 31
TI  - The Role of Glutamate Underlying Treatment-resistant Depression.
PG  - 429-446
LID - 10.9758/cpn.22.1034 [doi]
AB  - The monoamine hypothesis has significantly improved our understanding of mood 
      disorders and their treatment by linking monoaminergic abnormalities to the 
      pathophysiology of mood disorders. Even 50 years after the monoamine hypothesis 
      was established, some patients do not respond to treatments for depression, 
      including selective serotonin reuptake drugs. Accumulating evidence shows that 
      patients with treatment-resistant depression (TRD) have severe abnormalities in 
      the neuroplasticity and neurotrophic factor pathways, indicating that different 
      treatment approaches may be necessary. Therefore, the glutamate hypothesis is 
      gaining attention as a novel hypothesis that can overcome monoamine restrictions. 
      Glutamate has been linked to structural and maladaptive morphological alterations 
      in several brain areas associated with mood disorders. Recently, ketamine, an 
      N-methyl-D-aspartate receptor (NMDAR) antagonist, has shown efficacy in TRD 
      treatment and has received the U.S. Food and Drug Administration approval, 
      revitalizing psychiatry research. However, the mechanism by which ketamine 
      improves TRD remains unclear. In this review, we re-examined the glutamate 
      hypothesis, bringing the glutamate system onboard to join the modulation of the 
      monoamine systems, emphasizing the most prominent ketamine antidepressant 
      mechanisms, such as NMDAR inhibition and NMDAR disinhibition in GABAergic 
      interneurons. Furthermore, we discuss the animal models used in preclinical 
      studies and the sex differences in the effects of ketamine.
FAU - Kim, Jeongseop
AU  - Kim J
AUID- ORCID: 0000-0001-5281-7678
AD  - Emotion, Cognition & Behavior Research Group, Korea Brain Research Institute 
      (KBRI), Daegu, Korea.
AD  - Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology 
      (DGIST), Daegu, Korea.
FAU - Kim, Tae-Eun
AU  - Kim TE
AUID- ORCID: 0000-0001-5813-1132
AD  - Emotion, Cognition & Behavior Research Group, Korea Brain Research Institute 
      (KBRI), Daegu, Korea.
AD  - Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology 
      (DGIST), Daegu, Korea.
FAU - Lee, Seung-Hwan
AU  - Lee SH
AUID- ORCID: 0000-0003-0305-3709
AD  - Department of Psychiatry, Inje University Ilsan Paik Hospital, Goyang, Korea.
FAU - Koo, Ja Wook
AU  - Koo JW
AUID- ORCID: 0000-0001-6233-1583
AD  - Emotion, Cognition & Behavior Research Group, Korea Brain Research Institute 
      (KBRI), Daegu, Korea.
AD  - Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology 
      (DGIST), Daegu, Korea.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Korea (South)
TA  - Clin Psychopharmacol Neurosci
JT  - Clinical psychopharmacology and neuroscience : the official scientific journal of 
      the Korean College of Neuropsychopharmacology
JID - 101207332
PMC - PMC10335903
OTO - NOTNLM
OT  - Chronic stress
OT  - Glutamate hypothesis
OT  - Ketamine
OT  - Models
OT  - Sex characteristics
OT  - Treatment-resistant depression
OT  - animal
COIS- Conflicts of Interest No potential conflict of interest relevant to this article 
      was reported.
EDAT- 2023/07/10 06:42
MHDA- 2023/07/10 06:43
PMCR- 2023/08/31
CRDT- 2023/07/10 04:12
PHST- 2022/10/11 00:00 [received]
PHST- 2022/10/24 00:00 [revised]
PHST- 2022/10/25 00:00 [accepted]
PHST- 2023/07/10 06:43 [medline]
PHST- 2023/07/10 06:42 [pubmed]
PHST- 2023/07/10 04:12 [entrez]
PHST- 2023/08/31 00:00 [pmc-release]
AID - cpn.22.1034 [pii]
AID - cpn-21-3-429 [pii]
AID - 10.9758/cpn.22.1034 [doi]
PST - ppublish
SO  - Clin Psychopharmacol Neurosci. 2023 Aug 31;21(3):429-446. doi: 
      10.9758/cpn.22.1034.