PMID- 33825765
OWN - NLM
STAT- MEDLINE
DCOM- 20220217
LR  - 20220228
IS  - 1809-452X (Electronic)
IS  - 1516-4446 (Print)
IS  - 1516-4446 (Linking)
VI  - 44
IP  - 1
DP  - 2022 Jan-Feb
TI  - Does mismatch negativity have utility for NMDA receptor drug development in 
      depression?
PG  - 61-73
LID - 10.1590/1516-4446-2020-1685 [doi]
AB  - Rapid antidepressant effects associated with ketamine have shifted the landscape 
      for the development of therapeutics to treat major depressive disorder (MDD) from 
      a monoaminergic to glutamatergic model. Treatment with ketamine, an 
      N-methyl-D-aspartate (NMDA) receptor antagonist, may be effective, but has many 
      non-glutamatergic targets, and clinical and logistical problems are potential 
      challenges. These factors underscore the importance of manipulations of binding 
      mechanics to produce antidepressant effects without concomitant clinical side 
      effects. This will require identification of efficient biomarkers to monitor 
      target engagement. The mismatch negativity (MMN) is a widely used 
      electrophysiological signature linked to the activity of NMDA receptors (NMDAR) 
      in humans and animals and validated in pre-clinical and clinical studies of 
      ketamine. In this review, we explore the flexibility of the MMN and its 
      capabilities for reliable use in drug development for NMDAR antagonists in MDD. 
      We supplement this with findings from our own research with three distinct NMDAR 
      antagonists. The research described illustrates that there are important 
      distinctions between the mechanisms of NMDAR antagonism, which are further 
      crystallized when considering the paradigm used to study the MMN. We conclude 
      that the lack of standardized methodology currently prevents MMN from being ready 
      for common use in drug discovery. This manuscript describes data collected from 
      the following National Institutes of Health (NIH) and Veterans Affairs (VA) 
      studies: AV-101, NCT03583554; lanicemine, NCT03166501; ketamine, NCT02556606.
FAU - Murphy, Nicholas
AU  - Murphy N
AUID- ORCID: 0000-0003-1805-3082
AD  - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of 
      Medicine, Houston, TX, USA.
AD  - Michael E. DeBakey VA Medical Center, Houston, TX, USA.
AD  - The Menninger Clinic, Houston, TX, USA.
FAU - Lijffijt, Marijn
AU  - Lijffijt M
AUID- ORCID: 0000-0001-5760-1729
AD  - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of 
      Medicine, Houston, TX, USA.
AD  - Michael E. DeBakey VA Medical Center, Houston, TX, USA.
FAU - Ramakrishnan, Nithya
AU  - Ramakrishnan N
AUID- ORCID: 0000-0002-8674-1971
AD  - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of 
      Medicine, Houston, TX, USA.
AD  - Michael E. DeBakey VA Medical Center, Houston, TX, USA.
FAU - Vo-Le, Bylinda
AU  - Vo-Le B
AUID- ORCID: 0000-0002-0730-8388
AD  - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of 
      Medicine, Houston, TX, USA.
AD  - Michael E. DeBakey VA Medical Center, Houston, TX, USA.
FAU - Vo-Le, Brittany
AU  - Vo-Le B
AD  - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of 
      Medicine, Houston, TX, USA.
AD  - Michael E. DeBakey VA Medical Center, Houston, TX, USA.
FAU - Iqbal, Sidra
AU  - Iqbal S
AUID- ORCID: 0000-0002-3567-8669
AD  - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of 
      Medicine, Houston, TX, USA.
AD  - Michael E. DeBakey VA Medical Center, Houston, TX, USA.
FAU - Iqbal, Tabish
AU  - Iqbal T
AUID- ORCID: 0000-0002-0878-9558
AD  - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of 
      Medicine, Houston, TX, USA.
AD  - Michael E. DeBakey VA Medical Center, Houston, TX, USA.
FAU - O'Brien, Brittany
AU  - O'Brien B
AUID- ORCID: 0000-0001-8454-0132
AD  - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of 
      Medicine, Houston, TX, USA.
AD  - Michael E. DeBakey VA Medical Center, Houston, TX, USA.
FAU - Smith, Mark A
AU  - Smith MA
AD  - VistaGen Therapeutics, Inc., South San Francisco, CA, USA.
AD  - Medical College of Georgia, Augusta, GA, USA.
FAU - Swann, Alan C
AU  - Swann AC
AUID- ORCID: 0000-0001-9879-6198
AD  - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of 
      Medicine, Houston, TX, USA.
AD  - Michael E. DeBakey VA Medical Center, Houston, TX, USA.
FAU - Mathew, Sanjay J
AU  - Mathew SJ
AUID- ORCID: 0000-0002-2715-6641
AD  - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of 
      Medicine, Houston, TX, USA.
AD  - Michael E. DeBakey VA Medical Center, Houston, TX, USA.
AD  - The Menninger Clinic, Houston, TX, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03583554
SI  - ClinicalTrials.gov/NCT03166501
SI  - ClinicalTrials.gov/NCT02556606
GR  - I01 CX001205/CX/CSRD VA/United States
GR  - R61 MH110540/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Review
PL  - Brazil
TA  - Braz J Psychiatry
JT  - Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)
JID - 100895975
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Animals
MH  - Depression
MH  - *Depressive Disorder, Major/drug therapy
MH  - Drug Development
MH  - Humans
MH  - *Ketamine
MH  - Receptors, N-Methyl-D-Aspartate
PMC - PMC8827377
COIS- VistaGen Therapeutics provided the AV-101 and placebo capsules and analyzed 
      AV-101 metabolites (AV-101 study). Biohaven Pharmaceuticals provided the 
      investigational drug for the lanicemine study. SJM has served as a consultant to 
      Alkermes, Allergan, Axsome Therapeutics, Clexio Biosciences, Greenwich 
      Biosciences, Intra-Cellular Therapies, Janssen, Neurocrine, Perception 
      Neurosciences, Praxis Precision Medicines, and Sage Therapeutics. He has received 
      research support from Biohaven Pharmaceuticals and VistaGen Therapeutics. ML has 
      served as principal investigator for trials funded by NeuroRx and Vistagen 
      Therapeutics and has received financial support from the MEDVAMC and the 
      Department of Defense. MAS is an employee of VistaGen Therapeutics. The authors 
      report no conflicts of interest.
EDAT- 2021/04/08 06:00
MHDA- 2022/02/19 06:00
PMCR- 2021/04/05
CRDT- 2021/04/07 12:22
PHST- 2020/12/04 00:00 [received]
PHST- 2021/01/13 00:00 [accepted]
PHST- 2021/04/08 06:00 [pubmed]
PHST- 2022/02/19 06:00 [medline]
PHST- 2021/04/07 12:22 [entrez]
PHST- 2021/04/05 00:00 [pmc-release]
AID - S1516-44462021005010203 [pii]
AID - 10.1590/1516-4446-2020-1685 [doi]
PST - ppublish
SO  - Braz J Psychiatry. 2022 Jan-Feb;44(1):61-73. doi: 10.1590/1516-4446-2020-1685.