Research Topics
| Joseph CoyleSummaryAffiliation: Harvard University Country: USA Publications
Research Grants
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Detail Information
Publications
NMDA receptor and schizophrenia: a brief historyJoseph T Coyle
Department of Psychiatry and Neuroscience, Harvard Medical School, McLean Hospital, Belmont, MA, USA
Schizophr Bull 38:920-6. 2012....
The NMDA receptor glycine modulatory site: a therapeutic target for improving cognition and reducing negative symptoms in schizophreniaJoseph T Coyle
Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA 02478, USA
Psychopharmacology (Berl) 174:32-8. 2004..Thus, there is convincing evidence that the glycine modulatory site on the NMDA receptor is a valid therapeutic target for improving cognition and associated negative symptoms in schizophrenia...- Finding the intracellular signaling pathways affected by mood disorder treatmentsJoseph T Coyle
Harvard Medical School, Department of Psychiatry, McLean Hospital, Belmont, MA 02478, USA
Neuron 38:157-60. 2003..These insights should assist in understanding the pathophysiology of severe mood disorders as well as aid in the development of more effective treatments... - Ionotropic glutamate receptors as therapeutic targets in schizophreniaJoseph T Coyle
Curr Drug Targets CNS Neurol Disord 1:183-9. 2002..Preliminary results with an allosteric modulator of the AMPA subtype of glutamate receptor suggest enhanced cognitive functions in subjects treated with clozapine... - A brief overview of N-acetylaspartate and N-acetylaspartylglutamateJoseph T Coyle
Department of Psychiatry and Neuroscience, Harvard Medical School, McLean Hospital, 115 Mill St, Belmont, MA 02178-9106, USA
Adv Exp Med Biol 576:1-6; discussion 361-3. 2006 - Glutamate and schizophrenia: beyond the dopamine hypothesisJoseph T Coyle
Harvard Medical School, McLean Hospital, Belmont, Masschusetts 02478, USA
Cell Mol Neurobiol 26:365-84. 2006..5. Thus, hypofunction of the NMDA receptor, possibly on critical GABAergic inter-neurons, may contribute to the pathophysiology of schizophrenia... - Glial metabolites of tryptophan and excitotoxicity: coming ungluedJoseph T Coyle
Department of Psychiatry, Harvard Medical School, McLean Hospital, 115 Mill St, Belmont, MA 02478, USA
Exp Neurol 197:4-7. 2006 - The GABA-glutamate connection in schizophrenia: which is the proximate cause?Joseph T Coyle
Department of Psychiatry, Harvard Medical School, McLean Hospital, 115 Mill St, Belmont, MA 02478, USA
Biochem Pharmacol 68:1507-14. 2004..Electrophysiologic and pharmacologic studies suggest that the vulnerable NMDA receptors in schizophrenia may be concentrated on cortico-limbic GABAergic interneurons, thereby linking these two neuropathologic features of the disorder... - Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophreniaJoseph T Coyle
McLean Hospital, Belmont, Massachusetts 02478, USA
Ann N Y Acad Sci 1003:318-27. 2003..Thus, there is convincing evidence that hypofunction of a subset of NMDA receptors may contribute to the symptomatic features of schizophrenia... - Substance use disorders and Schizophrenia: a question of shared glutamatergic mechanismsJoseph T Coyle
Harvard Medical School, Department of Psychiatry, McLean Hospital, Belmont, MA 02478, USA
Neurotox Res 10:221-33. 2006..Given the role of NMDA receptors in the reward circuitry and in substance dependence, it is reasonable to speculate that NMDA receptor dysfunction is a shared pathologic process in schizophrenia and co-morbid SUDs... - What can a clock mutation in mice tell us about bipolar disorder?Joseph T Coyle
Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA
Proc Natl Acad Sci U S A 104:6097-8. 2007 - Beyond the dopamine receptor: novel therapeutic targets for treating schizophreniaJoseph T Coyle
Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA 02478, USA
Dialogues Clin Neurosci 12:359-82. 2010..Potential sites for pharmacologic intervention targeting glutatatergic, GABAergic, and cholinergic neurotransmission to treat these symptoms of schizophrenia are discussed... - Beyond in vitro data: a review of in vivo evidence regarding the allosteric potentiating effect of galantamine on nicotinic acetylcholine receptors in Alzheimer's neuropathologyJoseph T Coyle
Department of Psychiatry, Harvard Medical School, Belmont, MA 02478, USA
J Alzheimers Dis 11:491-507. 2007..The use of nAChR agonists and antagonists in some of these studies lends support to the proposed allosteric potentiating ligand activity of galantamine at nAChRs. This dual action of galantamine may account for its therapeutic profile... - Folate, homocysteine, and negative symptoms in schizophreniaDonald C Goff
Schizophrenia Program and Neurology Service, Massachusetts General Hospital, Boston, USA
Am J Psychiatry 161:1705-8. 2004.... - D-cycloserine added to clozapine for patients with schizophreniaD C Goff
Psychotic Disorders Program, Massachusetts General Hospital, Boston, USA
Am J Psychiatry 153:1628-30. 1996..The effects of D-cycloserine added to clozapine were assessed and compared with previous results for D-cycloserine plus conventional neuroleptics... - The nagging question of the function of N-acetylaspartylglutamateJ T Coyle
Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts 02178, USA
Neurobiol Dis 4:231-8. 1997..The levels of NAAG and the activity of carboxypeptidase II are altered in a regionally specific fashion in several neuropsychiatric disorders... - Increased glutamatergic neurotransmission and oxidative stress after alcohol withdrawalG E Tsai
Department of Psychiatry, Massachusetts General Hospital, Boston, USA
Am J Psychiatry 155:726-32. 1998..Whether glutamatergic neurotransmission and oxidative stress are enhanced during ethanol withdrawal in humans is unknown... - A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophreniaD C Goff
Massachusetts General Hospital, Harvard Consolidated Department of Psychiatry, Boston, USA
Arch Gen Psychiatry 56:21-7. 1999.... - Improved cognition in Alzheimer's disease with short-term D-cycloserine treatmentG E Tsai
Geriatric Neurobehavoral Clinic, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, USA
Am J Psychiatry 156:467-9. 1999..D-Cycloserine exhibits partial agonist activity at the glycine site of N-methyl-D-aspartate subtype glutamate receptor, facilitating activation of the receptor and improving cognition and memory... - D-serine added to clozapine for the treatment of schizophreniaG E Tsai
Laboratory of Molecular and Psychiatric Neuroscience, Mailman Research Center, McLean Hospital, Belmont, MA 02478, USA
Am J Psychiatry 156:1822-5. 1999..To study the difference between full and partial agonists at the NMDA receptor glycine site, the clinical effects of adding D-serine to clozapine were assessed... - Evidence for the presence of N-acetylaspartylglutamate in cultured oligodendrocytes and LPS activated microgliaL Passani
Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, Charlestown, MA 02129, USA
Brain Res 794:143-5. 1998..The findings indicate that NAAG is localized to specific glial cell types. Further our results suggest that NAAG biosynthesis is induced in microglia, activated by specific stimuli... - Modeling of context-dependent retrieval in hippocampal region CA1: implications for cognitive function in schizophreniaPeter J Siekmeier
Department of Psychiatry, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA
Schizophr Res 89:177-90. 2007..As such, it can shed light on the etiology of schizophrenia in a fundamental way, and also holds the promise of pointing the way to more effective treatments... - Isolation and expression of a rat brain cDNA encoding glutamate carboxypeptidase IIR Luthi-Carter
Department of Psychiatry, Massachusetts General Hospital East, Charlestown, MA 02129, USA
Proc Natl Acad Sci U S A 95:3215-20. 1998.... - Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidaseR E Carter
Department of Psychiatry, Massachusetts General Hospital East, Charlestown 02129, USA
Proc Natl Acad Sci U S A 93:749-53. 1996..These results also raise questions about the role of PSM in both normal and pathologic prostate epithelial-cell function... - Early embryonic death of glutamate carboxypeptidase II (NAALADase) homozygous mutantsG Tsai
Laboratory of Molecular and Psychiatric Neuroscience, Mailman Research Center, McLean Hospital Department of Psychiatry, Harvard Medical School, Cambridge, Massachusetts, USA
Synapse 50:285-92. 2003..The results indicate that the expression of glutamate carboxypeptidase II is upregulated when one allele is inactivated and that its activity is essential for early embryogenesis... - Targeted disruption of serine racemase affects glutamatergic neurotransmission and behaviorA C Basu
Department of Psychiatry, Harvard Medical School, Belmont, MA 02478, USA
Mol Psychiatry 14:719-27. 2009.... - Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophreniaJohn E Lisman
Department of Biology, Brandeis University, 415 South Street, Waltham, MA 02454, USA
Trends Neurosci 31:234-42. 2008..iii) Nicotine enhances the output of interneurons, and might thereby contribute to its therapeutic effect in schizophrenia... - Ube3a mRNA and protein expression are not decreased in Mecp2R168X mutant miceAmy Lawson-Yuen
Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA 02478, USA
Brain Res 1180:1-6. 2007..The male mice experience early death. Analysis of Ube3a mRNA and protein levels in the Mecp2(R168X) male mice showed no significant difference in expression compared to their wild type littermates... - L-type calcium channels reduce ROS generation in cerebellar granule cells following kainate exposureMichael L Leski
Laboratory of Molecular Neuroscience, McLean Hospital, Belmont, Massachusetts 02178, USA
Synapse 43:30-41. 2002.... - Endogenous N-acetylaspartylglutamate reduced NMDA receptor-dependent current neurotransmission in the CA1 area of the hippocampusRichard Bergeron
Ottawa Health Research Institute, Department of Psychiatry, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada
J Neurochem 100:346-57. 2007..All together, these results suggest that NAAG acts as an endogenous modulator of NMDARs in the CA1 area of the hippocampus... - Glutamatergic mechanisms in schizophreniaGuochuan Tsai
Laboratory of Molecular and Psychiatric Neuroscience, Mailman Research Center, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA
Annu Rev Pharmacol Toxicol 42:165-79. 2002..Thus, hypofunction of a subpopulation of cortico-limbic NMDA receptors may participate in the pathophysiology of schizophrenia... - Regulation of glutamate carboxypeptidase II function in corticolimbic regions of rat brain by phencyclidine, haloperidol, and clozapineCecilia Flores
Department of Psychiatry, Harvard Medical School and McLean Hospital, Mailman Research Center, Belmont, MA, USA
Neuropsychopharmacology 28:1227-34. 2003..These results demonstrate that psychotomimetic and neuroleptic drugs modulate GCP II function in brain regions that are widely involved in the neuropathology of schizophrenia... - Gene knockout of glycine transporter 1: characterization of the behavioral phenotypeGuochuan Tsai
Department of Psychiatry and Alcohol and Drug Abuse Research Center, McLean Hospital, Belmont, MA 02178, USA
Proc Natl Acad Sci U S A 101:8485-90. 2004.... - Glutamate carboxypeptidase II gene expression in the human frontal and temporal lobe in schizophreniaSubroto Ghose
Clinical Brain Disorders Branch, IRP, NIMH, NIH, Bethesda, MD 20892, USA
Neuropsychopharmacology 29:117-25. 2004..Our findings support the notion that the hydrolysis of NAAG is disrupted in schizophrenia and that specific anatomical regions may show discrete abnormalities in GCP II synthesis... - NMDA receptor function, neuroplasticity, and the pathophysiology of schizophreniaJoseph T Coyle
Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts, USA
Int Rev Neurobiol 59:491-515. 2004 - NAAG reduces NMDA receptor current in CA1 hippocampal pyramidal neurons of acute slices and dissociated neuronsRichard Bergeron
Ottawa Health Research Institute, Ottawa, ON, Canada
Neuropsychopharmacology 30:7-16. 2005..Moreover, in dissociated pyramidal neurons of the CA1 region, NAAG also reduced the NMDA current and this effect was reversed by glycine. These results suggest that NAAG reduces the NMDA currents in hippocampal CA1 pyramidal neurons... - Decoding schizophreniaDaniel C Javitt
Program in Cognitive Neuroscience and Schizophrenia, Nathan Kline Institute, Orangeburg, N.Y, USA
Sci Am 290:48-55. 2004 - Reduced glycine transporter type 1 expression leads to major changes in glutamatergic neurotransmission of CA1 hippocampal neurones in miceMarzia Martina
Departments of Cellular and Molecular Medicine, and Psychiatry, University of Ottawa, Ottawa, ON, Canada
J Physiol 563:777-93. 2005..Overall, these findings highlight the importance of GlyT1 in regulating glutamatergic neurotransmission... - Functional magnetic resonance imaging studies of schizophrenic patients during word production: effects of D-cycloserineDeborah A Yurgelun-Todd
Cognitive Neuroimaging Laboratory, Brain Imaging Center, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA
Psychiatry Res 138:23-31. 2005..These results suggest that the addition of D-cycloserine to conventional neuroleptics may improve negative symptoms through enhanced temporal lobe function... - Do maternal folate and homocysteine levels play a role in neurodevelopmental processes that increase risk for schizophrenia?Jonathan D Picker
Department of Genetics, Harvard Medical School McLean Hospital, Belmont, MA, USA
Harv Rev Psychiatry 13:197-205. 2005.... - Low cerebrospinal fluid glutamate and glycine in refractory affective disorderMark A Frye
Department of Psychiatry, University of California Los Angeles Neuropsychiatric Institute, Los Angeles, CA, USA
Biol Psychiatry 61:162-6. 2007..Glutamatergic dysregulation has been documented in schizophrenia but has received less systematic study in affective illness... - Treating a child with Asperger's disorder and comorbid bipolar disorderJean A Frazier
Department of Psychiatry, Harvard Medical School, Boston, MA, USA
Am J Psychiatry 159:13-21. 2002 - Depression and bipolar support alliance consensus statement on the unmet needs in diagnosis and treatment of mood disorders in children and adolescentsJoseph T Coyle
J Am Acad Child Adolesc Psychiatry 42:1494-503. 2003..National efforts are required to restructure healthcare delivery and provider training and to immediately develop more advanced research on pathophysiology, prevention, and services delivery effectiveness... - Getting balance: drugs for bipolar disorder share targetJoseph T Coyle
Nat Med 8:557-8. 2002 - Neurobiology of schizophreniaChristopher A Ross
Division of Neurobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA
Neuron 52:139-53. 2006..Understanding these basic pathologic processes may yield novel targets for the development of more effective treatments...
Research Grants
- PSYCHOSIS AND BRAIN GLUTAMATEJoseph Coyle; Fiscal Year: 2009..Findings from these studies should shed light on the pathophysiology of schizophrenia and may identify potential strategies for novel treatments. ..
- Computational CoreJoseph Coyle; Fiscal Year: 2007..abstract_text> ..
- PSYCHOSIS AND BRAIN GLUTAMATEJoseph Coyle; Fiscal Year: 2002..These studies should further clarify the role of NAAG in modulating brain glutamatergic neurotransmission that should have significant implications for neurodegenerative disorders, schizophrenia and epilepsy. ..
- PSYCHOSIS AND BRAIN GLUTAMATEJoseph T Coyle; Fiscal Year: 2011..He will use the model to clarify the underlying mechanisms, to determine how these mechanisms relate to other schizophrenic risk genes and to test potential treatments to correct these neuronal defects characteristic of schizophrenia. ..