- Lateralised glutamatergic and GABAergic abnormalities in caudate and thalamus, with right-sided Glu/Glx increases and opposing GABA changes.
- Asymmetric NAAG and NAA alterations: left thalamic NAAG markedly reduced, right thalamic NAAG elevated, with left-lateralised NAA reductions.
- Treatment-related findings: non-remitters showed lower baseline left thalamic and caudate NAA and GABA; thalamic Glu declined below control levels at follow-up.
Neuropsychopharmacology. 2026 Aug 10. doi: 10.1038/s41386-026-02522-y. Online ahead of print.
ABSTRACT
Despite growing evidence from magnetic resonance spectroscopy studies of glutamatergic and GABAergic abnormalities in schizophrenia, in vivo characterization of subcortical neurometabolites at ultra-high field and their longitudinal change across antipsychotic treatment remains limited. Ultra-high-field 7-Tesla (7 T) magnetic resonance spectroscopic imaging (MRSI) enables simultaneous multivoxel quantification of neurometabolites across subcortical regions implicated in schizophrenia, including the thalamus and dorsal caudate. Here, we leveraged 7 T MRSI to characterize subcortical neurometabolite profiles in 91 healthy individuals and 29 individuals with early-phase schizophrenia spectrum disorders (SSD) scanned while presenting with moderate to severe psychosis and following eight weeks of antipsychotic treatment. Primary analyses revealed lateralized alterations in glutamate (Glu) and GABA. In the caudate, Glu and Glx were elevated in the right hemisphere, while GABA was elevated on the right and reduced on the left, a dissociation observed in both the caudate and thalamus. Left thalamic Glx was also elevated, and Glu-GABA coupling was disrupted in the right thalamus. In secondary analyses, thalamic NAAG was markedly reduced in the left hemisphere, with elevation observed in the right thalamus, in addition to left-lateralized thalamic and caudate NAA reduction and elevated caudate GPC.Cho. In exploratory treatment-response analyses, non-remitters showed lower left thalamic and caudate NAA and GABA at baseline, with thalamic Glu declining below healthy control levels at follow-up only in non-remitters. Right thalamic NAAG elevation was restricted to the longer illness group. Collectively, these findings implicate an asymmetric disruption of astroglial-neuronal balance within subcortical regions in early-phase SSD, and across antipsychotic treatment.
PMID:42575941 | DOI:10.1038/s41386-026-02522-y
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