Glutamate & Dopamine: Biological Predictors of the Transition to Psychosis?

Philadelphia, PA, 30 September, 2010 - There is growing evidence that two neurotransmitters - dopamine and glutamate - are abnormal in people with psychotic illness, including schizophrenia. Among many other things, these chemicals play a role in cognitive functions, such as memory, learning, and problem-solving.

A new study in Biological Psychiatry is now the first to examine the relationship between these two brain chemicals by measuring both in the same individuals.

Dr. James Stone and colleagues studied people with sub-threshold psychotic symptoms, who were at very high risk of undergoing transition to full-blown psychotic illness, using two brain imaging techniques - magnetic resonance spectroscopy, which allows measurement of glutamate in the brain, and [18F]DOPA positron emission tomography, which gives a measure of dopamine neuron activity.

“By combining neuroimaging approaches, we may get new insights into the disturbances in brain circuits that contribute to the emergence of psychosis and the full schizophrenia syndrome from the less developed symptoms of the at-risk state,” commented Dr. John Krystal, Editor of Biological Psychiatry.

They found that in these individuals, lower glutamate in hippocampus, a major structure in the brain involved in memory, was associated with increased dopamine activity. This was in keeping with earlier animal models, and with clinical studies of hippocampal and striatal function in psychosis.

According to Dr. Stone, “the findings support the hypothesis of an abnormal relationship between the dopamine and glutamate neurotransmitter systems in individuals with psychosis, and suggest that the development of drugs targeting glutamatergic transmission may be useful in the early treatment of psychosis.”

The findings also suggest that this abnormal glutamate-dopamine relationship may be a risk marker for later transition to a psychotic disorder.

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Notes to Editors:
The article is “Altered Relationship Between Hippocampal Glutamate Levels and Striatal Dopamine Function in Subjects at Ultra High Risk of Psychosis” by James M. Stone, Oliver D. Howes, Alice Egerton, Joseph Kambeitz, Paul Allen, David J. Lythgoe, Ruth L. O'Gorman, Mary A. McLean, Gareth J. Barker, and Philip McGuire. Stone, Howes, Egerton, Kambeitz, Allen, Lythgoe, Gorman, Barker, and McGuire are affiliated with the Institute of Psychiatry, King's College London, United Kingdom. McLean is affiliated with University College London, United Kingdom. Stone, Howes, and Egerton are also from Hammersmith Hospital, Imperial College London, United Kingdom. The article appears in Biological Psychiatry, Volume 68, Issue 7 (October 1, 2010), published by Elsevier.

The authors’ disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D. is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available at  http://journals.elsevierhealth.com/webfiles/images/journals/bps/Biological-Psychiatry-Editorial-Disclosures-7-22-10.pdf.

Full text of the article mentioned above is available upon request. Contact Chris J. Pfister at c.pfister@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.

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