Glutamate and dopamine: biological predictors of the transition to psychosis?
01 October 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.
New research by Dr James Stone and colleagues, Institute of Psychiatry at King's, published in Biological Psychiatry today, is the first to examine the relationship between these two brain chemicals by measuring both in the same individuals.
The researchers 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.
Dr Stone said: 'By combining neuroimaging approaches we aimed to gain new insight 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.'
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.
Dr Stone said: 'Our 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. Furthermore, this abnormal glutamate-dopamine relationship may be a risk marker for later transition to a psychotic disorder.'
The paper "Altered Relationship Between Hippocampal Glutamate Levels and Striatal Dopamine Function in Subjects at Ultra High Risk of Psychosis" can be accessed here:
http://www.ncbi.nlm.nih.gov/pubmed/20638047
The authors are 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