This article is more than 5 years old. Information may no longer be current.

Glutamatergic, dopaminergic systems may be related in psychosis

Study findings published in The Lancet Psychiatry showed that the cortical dopaminergic and glutamatergic systems appear related in patients with first-episode psychosis.

“It has been proposed that in individuals with schizophrenia, glutamatergic dysfunction in the frontal cortex leads to negative and cognitive symptoms, and, via projections to the midbrain, disinhibits mesostriatal dopamine neurons, resulting in positive psychotic symptoms,” Sameer Jauhar, MRCPsych, department of psychological medicine, King’s College London, and colleagues wrote. “However, to our knowledge, no study has investigated whether striatal dopamine synthesis capacity and cortical glutamate concentrations are correlated in people with psychosis, or if this correlation is related to symptoms.”

Researchers conducted a cross-sectional multimodal imaging study on 28 individuals with first-episode psychosis and 28 healthy controls to determine the connection between anterior cingulate cortex glutamate concentrations and striatal dopamine synthesis capacity in those with first-episode psychosis.

Participants underwent ¹F-DOPA positron emission tomography, which measured striatal dopamine synthesis capacity, and proton magnetic resonance spectroscopy, which measured anterior cingulate cortex glutamate concentrations. The investigators examined symptoms via the Positive and Negative Syndrome Scale and examined the relationships between measures via linear regression.

Analysis revealed a significant inverse association between glutamate concentrations and striatal dopamine synthesis capacity in patients with psychosis (P = .03). This connection remained significant after adding age, gender, ethnicity and medication status to the model (P = .015). However, Jauhar and colleagues found no significant association between dopamine and glutamate measures in healthy controls.

Based on the Positive and Negative Syndrome Scale scores, positive psychotic symptoms were positively tied to striatal dopamine synthesis capacity (P = .046) and demonstrated an inverse connection with anterior cingulate glutamate concentrations (P = .03); however, the results showed no connections between negative symptoms.

“Our findings suggest glutamatergic and dopaminergic systems are closely related in patients with psychosis, in line with preclinical models, and support further studies to test the effect of modulating cortical glutamate in the treatment of psychosis,” Jauhar and colleagues wrote. “Longitudinal studies are now required to establish the direction of causality.” – by Savannah Demko

Disclosure: Jauhar reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.