The relationship between neuromelanin, glutamate, and GABA in first-episode psychosis: A multimodal magnetic resonance imaging study.

Publication Type	Academic Article
Authors	Reyes-Madrigal F, León-Ortiz P, Wengler K, Bachmann H, Singletary N, Ortuño M, Mao X, Rivera-Chávez L, Malacara M, Shungu D, Horga G, Fuente-Sandoval C
Journal	Biol Psychiatry Cogn Neurosci Neuroimaging
Date Published	11/12/2025
ISSN	2451-9030
Abstract	BACKGROUND: In vivo neuroimaging studies documenting the relationship between dopamine and γ-aminobutyric acid (GABA) or glutamate in schizophrenia are scarce and frequently involve 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 of dopaminergic function, in the substantia nigra and ventral tegmental area (SN-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 first-episode psychosis (FEP) patients and 22 age- and sex-matched healthy controls. 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: Among participants, the SN-VTA NM-MRI contrast in the substantia nigra showed a positive correlation with Glx in the striatum; striatal GABA levels were not associated with NM-MRI contrast. In the medial prefrontal cortex, we failed to identify correlations between Glx or GABA with NM-MRI contrast. CONCLUSIONS: The present study provides preliminary evidence of the association between striatal glutamate and a novel validated proxy for dopaminergic function in antipsychotic-naïve FEP individuals. Future research, using a longitudinal design, on these combined MRI biomarkers as predictors of treatment response is warranted.
DOI	10.1016/j.bpsc.2025.10.019
PubMed ID	41238118