Could the neurotransmitter glutamate, not dopamine, be the major
neurotransmitter culprit in schizophrenia? In other words, might glutamate
damage the brain and then involve the neurotransmitter dopamine, which has
been strongly implicated in schizophrenia?
Quite possibly, a study reported in the June American Journal of
Psychiatry suggests. Glutamate levels were found to be significantly
higher in the brains of teens at high genetic risk for schizophrenia than in
the brains of teens not at such risk.
The study was headed by Philip Tibbo, M.D., an assistant professor of
psychiatry at the University of Alberta in Edmonton, Canada.
Tibbo and his coworkers used a technique called 3-T proton magnetic
resonance spectroscopy (H-MRS) to measure glutamate levels in the brains of 20
adolescents at high genetic risk for schizophrenia because they had a parent
with schizophrenia, as well as in the brains of 22 teens without such genetic
risk. The region of the brain chosen for glutamate assessment was the medial
prefrontal cortex, because it receives glutamate inputs from the thalamus, as
well as from other brain regions that have shown structural abnormalities in
Glutamate levels were found to be significantly higher in the medial
prefrontal cortex of the teens at high genetic risk for schizophrenia than in
the teens not at such risk.
The finding supports the hypothesis that "glutamate system
dysfunction may play a role in neuroarchitectural abnormalities seen in
schizophrenia...," Tibbo and his team concluded.
These results do not have practical implications for clinical psychiatrists
at this time, Tibbo told Psychiatric News. In other words,
psychiatrists cannot put teens at genetic risk for schizophrenia in an H-MRS
scanner to see whether they have abnormally high levels of glutamate in their
brains. However, it may eventually be possible to do so "if techniques
improve and [glutamate] correlations are made with cognitive tests,"
In fact, he added, "I am currently writing a manuscript that has
results from this same group two years later.... It indicates that changes in
glutamate over time correlate with results on cognitive testing."
Still other evidence beside that of Tibbo and his colleagues has been
building for the hypothesis that glutamate plays a notable role in
schizophrenia. For instance, three proteins are used for reuptake of glutamate
by brain neurons. Greater genetic expression for two out of three of the
proteins has been found in postmortem thalamus tissue taken from schizophrenia
patients than in postmortem thalamus tissue taken from healthy control
subjects (Psychiatric News, September 21, 2001).
The study was funded by the National Alliance for Research on Schizophrenia
and Affective Disorders.
The study, "3-T Proton MRS Investigation of Glutamate and
Glutamine in Adolescents at High Genetic Risk for Schizophrenia," is
posted online at<http://ajp.psychiatryonline.org/cgi/content/abstract/161/6/1116>.▪
Am J Psychiatry