Glutamatergic transmission in schizophrenia: from basic research to clinical practice.
paper
Cited
Public
- Authors
- Kantrowitz, Joshua; Javitt, Daniel C
- Year
- 2012
- Journal
- Current opinion in psychiatry
- PMID
- 22297716
- DOI
- 10.1097/YCO.0b013e32835035b2
- PMCID
- PMC5224527
PURPOSE OF REVIEW: The past 20 years have seen the glutamatergic hypothesis go from theory to phase III trials of novel mechanism antipsychotics. RECENT FINDINGS: We review the recent literature on glutamatergic theory, covering assessment and genetic studies, as well as drug development in animals and humans. SUMMARY: Although evidence continues to accumulate in support of glutamate hypotheses, further research continues to be required and interactions with other key systems need to be explored.
Schematic model of the N-methyl-D-aspartate (NMDA) receptor complex and synaptic glutamate ( ), D-serine ( ), and glycine ( ) regulation and metabolism. The nonphysiologic NMDA antagonist PCP and ketamine site is also shown. DAOA, D-amino acid oxidase activator; PCP, phencyclidine. Reproduced from [2].
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) outcomes for high-dose D-serine. Baseline (filled bars) and final (open bars) normalized MATRICS domains and overall mean composite (mean T-score of six tested domains) for (a) 30, (b) 60, and (c) 120 mg/kg. (d) Within group effect sizes for each dose. *P <0.05 in a paired t-test between baseline and final (aβc) or in a paired t-test for doses more than 60 mg/kg (d). #Significant (P <0.05) dose by time interaction for 30 vs. 60 mg/kg or more. Reproduced from [29βͺ].
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| Name | Type |
|---|---|
| age-matched and sex-matched controls local | cohort |
| Age-matched controls local | cohort |
| alanine local | drug |
| AMPA receptor | drug |
| antipsychotics | drug |
| anxiety | phenotype |
| auditory hallucinations | phenotype |
| Auditory processing | anatomy |
| Belief conviction local | phenotype |
| Biomarkers | phenotype |
| biphenyl indanone-A local | drug |
| Brain glycine levels local | phenotype |
| Caucasians | cohort |
| caudateβputamen local | anatomy |
| CDPPB local | drug |
| clozapine | drug |
| cognition | phenotype |
| Cognitive set-shifting ability local | phenotype |
| cortex | anatomy |
| CX516 local | drug |
| D1 receptor | drug |
| DAAO inhibitor local | drug |
| D-amino acid oxidase local | gene |
| D-amino acid-oxidase-related genes local | gene |
| DARPP-32 | drug |
| D-cycloserine | drug |
| delusional distress local | phenotype |
| Delusional distress local | phenotype |
| delusional severity local | phenotype |
| Delusional severity local | phenotype |
| Disordered cognition local | phenotype |
| Dizocilpine (MK-801) local | drug |
| dopamine | drug |
| d-serine | drug |
| DTNBP1 | gene |
| Dysbindin mutant mice local | cohort |
| ERP | phenotype |
| forebrain | anatomy |
| Fos-like immunoreactivity local | phenotype |
| frontal cortex | anatomy |
| general cognitive functioning local | phenotype |
| glutamate | drug |
| Glutamatergic treatment trials local | cohort |
| glutathione | drug |
| glutathione-synthesis-related genes local | gene |
| glycine | drug |
| glycine-site agonist local | drug |
| glycine transport inhibitor local | drug |
| Glycine transport inhibitor local | drug |
| GRIN1 | gene |
| GRIN2B | gene |
| GRM5 | gene |
| haloperidol | drug |
| healthy controls | cohort |
| Healthy participants (n=16) local | cohort |
| Heschl's gyrus | anatomy |
| hippocampus | anatomy |
| humans | cohort |
| hyperlocomotion | phenotype |
| Ionotropic receptors local | drug |
| Japanese population | cohort |
| kainate receptor | drug |
| ketamine | drug |
| Lateral septal nucleus local | anatomy |
| Left superior temporal cortex local | anatomy |
| l-serine | drug |
| LY2140023 monohydrate local | drug |
| Measurement and Treatment Research to Improve Cognition in Schizophrenia score local | phenotype |
| mediodorsal thalamus local | anatomy |
| memantine | drug |
| Metabotropic receptors local | drug |
| mGlu2/3 agonists | drug |
| mGlu2 positive allosteric modulators local | drug |
| mGlu5 receptor | drug |
| mice | cohort |
| Misattribution errors local | phenotype |
| mismatch negativity | phenotype |
| MK-801 local | drug |
| N1 local | phenotype |
| N-acetylcysteine | drug |
| Neboglamine local | drug |
| negative symptoms | phenotype |
| neuropathic pain | phenotype |
| NMDA | drug |
| NMDA antagonist | drug |
| NMDA-based treatment local | drug |
| NMDA-based treatments local | drug |
| NMDA evoked currents local | phenotype |
| NMDA function local | phenotype |
| NMDA receptor | drug |
| NMDA-related genes local | gene |
| nonacute-schizophrenia patients local | cohort |
| nonclozapine antipsychotics local | drug |
| novel object detection local | phenotype |
| NR1 | gene |
| nucleus accumbens | anatomy |
| order memory local | phenotype |
| other ethnic groups local | cohort |
| P1 local | phenotype |
| P300 measures | phenotype |
| Pain thresholds local | phenotype |
| PANSS local | phenotype |
| PANSS general local | phenotype |
| PANSS negative local | phenotype |
| PANSS positive local | phenotype |
| PANSS total symptoms local | phenotype |
| PCP | drug |
| Perseverative responding local | phenotype |
| phase III studies local | cohort |
| phase II study local | cohort |
| phencyclidine | drug |
| phenylalanine | drug |
| plasma D-serine levels local | other |
| positive symptoms | phenotype |
| preattentive processing local | phenotype |
| prefrontal cortex | anatomy |
| prepulse inhibition | phenotype |
| pyramidal neurons | anatomy |
| rats | cohort |
| rearing behavior | phenotype |
| recognition memory | phenotype |
| relational memory local | phenotype |
| RG1478 local | drug |
| RG1678 | drug |
| Rostral agranular insular cortex local | anatomy |
| sarcosine | drug |
| schizophrenia | phenotype |
| Sensory processing local | phenotype |
| serine racemase local | gene |
| serotonin | drug |
| Sleep architecture local | phenotype |
| sociability | phenotype |
| social memory | phenotype |
| social novelty local | phenotype |
| spatial working memory | phenotype |
| striatum | anatomy |
| superior temporal gyrus | anatomy |
| tolerance | phenotype |
| total symptoms local | phenotype |
| treatment-resistant schizophrenia local | phenotype |
| Tryptophan local | drug |
| tyrosine | drug |
| visual processing | phenotype |
| visual sensory areas local | anatomy |
| working memory | phenotype |
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