The Relationship Between Neuromelanin, Glutamate, and GABA in First-Episode Psychosis: A Multimodal Magnetic Resonance Imaging Study.

BACKGROUND: In vivo neuroimaging studies documenting the relationship between dopamine and GABA (gamma-aminobutyric acid) or glutamate in schizophrenia are scarce and have often involved patients in chronic phases of the disorder, which complicates distinguishing medication effects from illness progression. METHODS: We examined the contrast ratio of neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a proxy for dopaminergic function, in the substantia nigra (SN) and ventral tegmental area (VTA) and its association with striatal and medial prefrontal GABA and the sum of glutamate and glutamine (Glx), measured by proton magnetic resonance spectroscopy, in 23 never-medicated patients with first-episode psychosis (FEP) and 22 age- and sex-matched healthy control participants. All participants were recruited at the Instituto Nacional de Neurología y Neurocirugía in Mexico City. All imaging studies were performed on a 3T MRI scanner. RESULTS: The SN-VTA NM-MRI contrast showed a positive correlation with Glx in the striatum; striatal GABA levels were not associated with the NM-MRI contrast. In the medial prefrontal cortex, we failed to identify correlations between Glx or GABA and the NM-MRI contrast. CONCLUSIONS: The current study provides preliminary evidence of the association between striatal glutamate and a novel validated proxy for dopaminergic function in antipsychotic-naïve individuals with FEP. Future research, using a longitudinal design, on these combined MRI biomarkers as predictors of treatment response is warranted.