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The relationship between cortical glutamate and striatal dopamine function in first episode psychosis: a multi-modal PET and MRS imaging study

Research output: Contribution to journalArticle

Original languageEnglish
JournalThe Lancet Psychiatry
Publication statusSubmitted - 2018

King's Authors


Background: The pathophysiology of psychosis remains incompletely understood. Disruption in cortical glutamatergic signalling precipitating aberrant striatal dopamine function is a proposed model, but has not been tested in vivo. We therefore aimed to test the relationship between glutamate and dopamine function, and psychotic symptoms.
Methods: Twenty-eight individuals with first episode psychosis and twenty healthy controls received 18F-DOPA positron emission tomography (measuring striatal dopamine synthesis capacity), and proton magnetic resonance spectroscopy (measuring anterior cingulate cortex glutamate levels). Symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Linear regression was used to examine relationships between measures.
Outcome: Glutamate concentrations showed a statistically significant inverse relationship with striatal dopamine synthesis capacity (R2=0.13, p=0.03). This relationship remained significant after the addition of age, gender, ethnicity and medication status to the model (p=0.014). In controls, there was no significant relationship between dopamine and glutamate measures (R2=0.04, p=0.39). Positive psychotic symptoms were positively associated with striatal dopamine synthesis capacity (R2=0.14, p=0.046) and showed an inverse relationship with anterior cingulate glutamate levels (R2=0.16, p=0.03). No relationships were seen with negative symptoms.

Interpretation: These observations are consistent with the hypothesis that cortical glutamate dysfunction is related to subcortical dopamine function and psychosis.

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