Glutamate dysfunction in people with prodromal symptoms of psychosis: relationship to gray matter volume.
BACKGROUND
The glutamate model of schizophrenia proposes that altered glutamatergic neurotransmission is fundamental to the development of the disorder. In addition, its potential to mediate neurotoxicity raises the possibility that glutamate dysfunction could underlie neuroanatomic changes in schizophrenia. Here we determine whether changes in brain glutamate are present in subjects at ultra high risk of developing psychosis and whether these changes are related to reductions in cortical gray matter volume.


METHODS
Twenty-seven individuals with an at-risk mental state and a group of 27 healthy volunteers underwent proton magnetic resonance spectroscopy and volumetric proton magnetic resonance imaging using a 3-Tesla scanner. Glutamate and glutamine levels were measured in anterior cingulate, left hippocampus, and left thalamus. These measures were then related to cortical gray matter volume.


RESULTS
At-risk mental state (ARMS) subjects had significantly lower levels of glutamate than control subjects in the thalamus (p < .05) but higher glutamine in the anterior cingulate (p < .05). Within the ARMS group, the level of thalamic glutamate was directly correlated with gray matter volume in the medial temporal cortex and insula (p < .01).


CONCLUSIONS
This study provides the first evidence that brain glutamate function is perturbed in people with prodromal signs of schizophrenia and that glutamatergic dysfunction is associated with a reduction in gray matter volume in brain regions thought to be critical to the pathogenesis of the disorder. These findings support the hypothesis that drugs affecting the glutamate system may be of benefit in the early stages of psychotic illness.
Stone
James M
JM
Institute of Psychiatry, King's College London, University College London, United Kingdom. james.stone@iop.kcl.ac.uk
Day
Fern
F
Tsagaraki
Helen
H
Valli
Isabel
I
McLean
Mary A
MA
Lythgoe
David J
DJ
O'Gorman
Ruth L
RL
Barker
Gareth J
GJ
McGuire
Philip K
PK
D000328:Adult; D001931:Brain Mapping; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D001523:Mental Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011522:Protons; D011569:Psychiatric Status Rating Scales; D012306:Risk; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D013788:Thalamus / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
D011522:Protons; D005973:Glutamine; D018698:Glutamic Acid