Nav: Home

Glutamate: Too much of a good thing in schizophrenia?

October 27, 2008

Philadelphia, PA, October 27, 2008 - Is schizophrenia a disorder of glutamate hyperactivity or hypoactivity? While the predominant hypothesis for many years was that schizophrenia was a glutamate deficit disorder, there is growing evidence of glutamate hyperactivity as well. The study by Karlsson et al., appearing in the November 1st issue of Biological Psychiatry, reinforces this point with new data about the impact of deleting the gene for the glutamate transporter EAAT1. EAAT1, implicated in schizophrenia, plays a critical role in inactivating glutamate by removing it from the synaptic and extracellular spaces. The authors demonstrate that these "knockout" animals show increased responses to the NMDA glutamate receptor antagonist, MK-801. This drug causes the release of more glutamate into the synapse in the frontal cortex. This effect of MK-801 is reduced by a group II metabotropic glutamate receptor agonist, which reduces glutamate release. Dr. Andrew Holmes, corresponding author, further discusses their findings, "Our study adds a new twist to [glutamate] research by showing that genetically disrupting a major regulator of glutamate's ability to communicate between nerve cells produces certain 'schizophrenia-like' features in mice and, moreover, that these abnormalities can be corrected by a highly promising new class of glutamate-targeting antipsychotic treatments." In fact, this class of drugs has already shown some preliminary efficacy in its ability to treat individuals suffering from schizophrenia.

John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, comments: "The NMDA receptor antagonist model and the EAAT1 knockout animal push us to take a fresh look at the obstacles to treating cognitive impairments associated with schizophrenia, in other words, optimizing their cortical network function. This new look can lead us to drugs that would have been completely surprising as recently as 10 years ago, such as the group II metabotropic glutamate receptor agonists."

Dr. Holmes does note that further research is warranted, stating, "What is now needed is more research to get a better handle on how disrupting this gene affects the brain's neural wiring and molecular signaling pathways to produce the symptoms of schizophrenia." This finding could ultimately help scientists develop new or improved treatments for this schizophrenia.
-end-
Notes to Editors:

The article is "Loss of Glial Glutamate and Aspartate Transporter (Excitatory Amino Acid Transporter 1) Causes Locomotor Hyperactivity and Exaggerated Responses to Psychotomimetics: Rescue by Haloperidol and Metabotropic Glutamate 2/3 Agonist" by Rose-Marie Karlsson, Kohichi Tanaka, Markus Heilig, and Andrew Holmes. Drs. Karlsson and Heilig are affiliated with the Laboratory for Clinical and Translational Studies, National Institute on Alcoholism and Alcohol Abuse, National Institutes of Health, Bethesda, Maryland. Dr. Holmes is from the Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse, National Institutes of Health, Rockville, Maryland. Dr. Tanaka is affiliated with the Laboratory of Molecular Neuroscience, School of Biomedical Science and Medical Research Institute, Tokyo Medical and Dental University Bunkyo-ku, Tokyo, Japan. The article appears in Biological Psychiatry, Volume 64, Issue 9 (November 1, 2008), published by Elsevier.

The authors' disclosures of financial and conflicts of interests are available in the article. Dr. Krystal's disclosures of financial and conflicts of interests are available http://journals.elsevierhealth.com/webfiles/images/journals/bps/Biological_Psychiatry_Editorial_Disclosures_08_01_08.pdfFull text of the article mentioned above is available upon request. Contact Jayne M. Dawkins at (215) 239-3674 or ja.dawkins@elsevier.com to obtain a copy or to schedule an interview.

About Biological Psychiatry

This international rapid-publication journal is the official journal of the Society of Biological Psychiatry. It covers a broad range of topics in psychiatric neuroscience and therapeutics. Both basic and clinical contributions are encouraged from all disciplines and research areas relevant to the pathophysiology and treatment of major neuropsychiatric disorders. Full-length and Brief Reports of novel results, Commentaries, Case Studies of unusual significance, and Correspondence and Comments judged to be of high impact to the field are published, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Concise Reviews and Editorials that focus on topics of current research and interest are also published rapidly.

Biological Psychiatry (http://www.sobp.org/journal) is ranked 4th out of the 95 Psychiatry titles and 16th out of 199 Neurosciences titles on the 2006 ISI Journal Citations Reports® published by Thomson Scientific.

About Elsevier

Elsevier is a world-leading publisher of scientific, technical and medical information products and services. Working in partnership with the global science and health communities, Elsevier's 7,000 employees in over 70 offices worldwide publish more than 2,000 journals and 1,900 new books per year, in addition to offering a suite of innovative electronic products, such as ScienceDirect (http://www.sciencedirect.com/), MD Consult (http://www.mdconsult.com/), Scopus (http://www.info.scopus.com/), bibliographic databases, and online reference works.

Elsevier (http://www.elsevier.com/) is a global business headquartered in Amsterdam, The Netherlands and has offices worldwide. Elsevier is part of Reed Elsevier Group plc (http://www.reedelsevier.com/), a world-leading publisher and information provider. Operating in the science and medical, legal, education and business-to-business sectors, Reed Elsevier provides high-quality and flexible information solutions to users, with increasing emphasis on the Internet as a means of delivery. Reed Elsevier's ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).

Elsevier

Related Schizophrenia Articles:

Dietary supplement may help with schizophrenia
A dietary supplement, sarcosine, may help with schizophrenia as part of a holistic approach complementing antipsychotic medication, according to a UCL researcher.
Schizophrenia: Adolescence is the game-changer
Schizophrenia may be related to the deletion syndrome. However, not everyone who has the syndrome necessarily develops psychotic symptoms.
Study suggests overdiagnosis of schizophrenia
In a small study of patients referred to the Johns Hopkins Early Psychosis Intervention Clinic (EPIC), Johns Hopkins Medicine researchers report that about half the people referred to the clinic with a schizophrenia diagnosis didn't actually have schizophrenia.
The ways of wisdom in schizophrenia
Researchers at UC San Diego School of Medicine report that persons with schizophrenia scored lower on a wisdom assessment than non-psychiatric comparison participants, but that there was considerable variability in levels of wisdom, and those with higher scores displayed fewer psychotic symptoms.
Recognizing the uniqueness of different individuals with schizophrenia
Individuals diagnosed with schizophrenia differ greatly from one another. Researchers from Radboud university medical center, along with colleagues from England and Norway, have demonstrated that very few identical brain differences are shared amongst different patients.
Resynchronizing neurons to erase schizophrenia
Today, a decisive step in understanding schizophrenia has been taken.
Genetics researchers close in on schizophrenia
Researchers at the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University have discovered 50 new gene regions that increase the risk of developing schizophrenia.
Looking for the origins of schizophrenia
Schizophrenia may be related to neurodevelopment changes, including brain's inability to create the appropriate vascular system, according to new study resulted from a partnership between the D'Or Institute for Research and Education, the University of Chile and the Federal University of Rio de Janeiro (UFRJ).
Researchers uncover novel mechanism behind schizophrenia
An international team of researchers led by a Case Western Reserve University School of Medicine scientist has uncovered a novel mechanism in which a protein--neuregulin 3--controls how key neurotransmitters are released in the brain during schizophrenia.
A new genetic marker for schizophrenia
Japanese scientists find a rare genetic variant that shows strong association with schizophrenia.
More Schizophrenia News and Schizophrenia Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#542 Climate Doomsday
Have you heard? Climate change. We did it. And it's bad. It's going to be worse. We are already suffering the effects of it in many ways. How should we TALK about the dangers we are facing, though? Should we get people good and scared? Or give them hope? Or both? Host Bethany Brookshire talks with David Wallace-Wells and Sheril Kirschenbaum to find out. This episode is hosted by Bethany Brookshire, science writer from Science News. Related links: Why Climate Disasters Might Not Boost Public Engagement on Climate Change on The New York Times by Andrew Revkin The other kind...
Now Playing: Radiolab

An Announcement from Radiolab