Altered relationship between hippocampal glutamate levels and striatal dopamine function in subjects at ultra high risk of psychosis.
BACKGROUND
Animal models of psychosis propose that striatal hyperdopaminergia is driven by abnormalities in hippocampal glutamatergic neurotransmission, but this has never been tested in humans.


METHODS
Sixteen individuals with an at-risk mental state for psychosis (ARMS) and 12 control subjects underwent proton magnetic resonance spectroscopy to estimate hippocampal glutamate and [18F]DOPA positron emission tomography to index striatal dopamine function. The relationship between hippocampal glutamate and striatal dopamine, as well as their relationship with prodromal symptoms, was determined using linear regression.


RESULTS
In ARMS subjects, but not controls, there was a significant negative relationship between hippocampal glutamate levels and striatal [18F]DOPA uptake (p = .03). Within the ARMS sample, striatal [18F]DOPA uptake was correlated with severity of abnormal beliefs (p = .03), there was a trend for hippocampal glutamate levels to be correlated with disordered speech (p = .06) and a trend for the interaction between hippocampal glutamate and [18F]DOPA uptake to predict later transition to psychosis (p = .07).


CONCLUSIONS
The relationship between hippocampal glutamate and striatal dopamine systems is altered in people at high risk of psychosis, and the degree to which it is changed may be related to the risk of transition to psychosis. Pharmacologic modulation of the glutamate system before the onset of psychosis might ameliorate this risk.
Stone
James M
JM
Department of Psychosis Studies, Institute of Psychiatry, King's College London, United Kingdom.
Howes
Oliver D
OD
Egerton
Alice
A
Kambeitz
Joseph
J
Allen
Paul
P
Lythgoe
David J
DJ
O'Gorman
Ruth L
RL
McLean
Mary A
MA
Barker
Gareth J
GJ
McGuire
Philip
P
D001931:Brain Mapping; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008954:Models, Biological; D049268:Positron-Emission Tomography / Q000379:methods; D011522:Protons; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000473:pathology*; D019275:Radiopharmaceuticals / Q000378:metabolism; D012306:Risk
D011522:Protons; D019275:Radiopharmaceuticals; D018698:Glutamic Acid; D004295:Dihydroxyphenylalanine; D004298:Dopamine