PMID- 11115327
OWN - NLM
STAT- MEDLINE
DCOM- 20010202
LR  - 20220316
IS  - 0003-990X (Print)
IS  - 0003-990X (Linking)
VI  - 57
IP  - 12
DP  - 2000 Dec
TI  - Ketamine-induced deficits in auditory and visual context-dependent processing in 
      healthy volunteers: implications for models of cognitive deficits in 
      schizophrenia.
PG  - 1139-47
AB  - BACKGROUND: In patients with schizophrenia, deficient generation of mismatch 
      negativity (MMN)-an event-related potential (ERP) indexing auditory sensory 
      ("echoic") memory-and a selective increase of "context dependent" ("BX") errors 
      in the "A-X" version of the Continuous Performance Test (AX-CPT) indicate an 
      impaired ability to form and use transient memory traces. Animal and human 
      studies implicate deficient N-methyl-D-aspartate receptor (NMDAR) functioning in 
      such abnormalities. In this study, effects of the NMDAR antagonists ketamine on 
      MMN generation and AX-CPT performance were investigated in healthy volunteers to 
      test the hypothesis that NMDARs are critically involved in human MMN generation, 
      and to assess the nature of ketamine-induced deficits in AX-CPT performance. 
      METHODS: In a single-blind placebo-controlled study, 20 healthy volunteers 
      underwent an infusion with subanesthetic doses of ketamine. The MMN-to-pitch and 
      MMN-to-duration deviants were obtained while subjects performed an AX-CPT. 
      RESULTS: Ketamine significantly decreased the peak amplitudes of the MMN-to-pitch 
      and MMN-to-duration deviants by 27% and 21%, respectively. It induced performance 
      deficits in the AX-CPT characterized by decreased hit rates and specific 
      increases of errors (BX errors), reflecting a failure to form and use transient 
      memory traces of task relevant information. CONCLUSIONS: The NMDARs are 
      critically involved in human MMN generation. Deficient MMN in schizophrenia thus 
      suggests deficits in NMDAR-related neurotransmission. N-methyl-D-aspartate 
      receptor dysfunction may also contribute to the impairment of patients with 
      schizophrenia in forming and using transient memory traces in more complex tasks, 
      such as the AX-CPT. Thus, NMDAR-related dysfunction may underlie deficits in 
      transient memory at different levels of information processing in schizophrenia. 
      Arch Gen Psychiatry. 2000;57:1139-1147.
FAU - Umbricht, D
AU  - Umbricht D
AD  - Psychiatric University Hospital, Department of Research, PO Box 68, Zurich 8029, 
      Switzerland. umbricht@bli.unizh.ch
FAU - Schmid, L
AU  - Schmid L
FAU - Koller, R
AU  - Koller R
FAU - Vollenweider, F X
AU  - Vollenweider FX
FAU - Hell, D
AU  - Hell D
FAU - Javitt, D C
AU  - Javitt DC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arch Gen Psychiatry
JT  - Archives of general psychiatry
JID - 0372435
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Adult
MH  - Auditory Perception/*drug effects
MH  - Cognition/*drug effects
MH  - Cognition Disorders/chemically induced
MH  - Evoked Potentials/drug effects
MH  - Female
MH  - Humans
MH  - Ketamine/*pharmacology
MH  - Male
MH  - Memory/drug effects
MH  - Memory Disorders/chemically induced
MH  - Models, Psychological
MH  - *Neuropsychological Tests
MH  - Psychomotor Performance/drug effects
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors/physiology
MH  - Schizophrenia/diagnosis/physiopathology
MH  - Schizophrenic Psychology
MH  - Visual Perception/*drug effects
EDAT- 2000/12/15 11:00
MHDA- 2001/03/03 10:01
CRDT- 2000/12/15 11:00
PHST- 2000/12/15 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2000/12/15 11:00 [entrez]
AID - yoa9366b [pii]
AID - 10.1001/archpsyc.57.12.1139 [doi]
PST - ppublish
SO  - Arch Gen Psychiatry. 2000 Dec;57(12):1139-47. doi: 10.1001/archpsyc.57.12.1139.