- Higher anterior cingulate GABA levels in first-trial responders versus non-responders, significantly associated with clinical treatment response.
- First-trial failures exhibited hyperactive visual network functional connectivity compared with responders.
- Positive correlation between ACC GABA and connectivity in non-responders suggests altered GABA from inhibitory to facilitative, supporting investigation of GABAergic therapies.
Schizophr Res. 2026 Sep 19;297:551-560. doi: 10.1016/j.schres.2026.09.014. Online ahead of print.
ABSTRACT
BACKGROUND: The anterior cingulate cortex (ACC) is implicated in schizophrenia, and gamma aminobutyric acid (GABA) in the ACC may differentially affect functional connectivity in patients. However, its association with treatment response remains poorly understood. Here, we examined their relationship and their association with treatment response in patients with differential efficacy.
METHODS: This study included 87 first-episode schizophrenia patients who underwent MRI scans to evaluate functional connectivity and neurotransmitter levels in the ACC. Participants were randomized to one antipsychotic and assessed for symptom severity at baseline and week 8, with them categorized into first trial response (FTR) group (n = 52) and first trial failed (FTF) group (n = 35) based on treatment response.
RESULTS: Our results revealed GABA levels in the ACC were significantly higher in FTR than FTF patients, and indicated that higher GABA levels were a significant associated with for clinical response. Hyperactive functional connectivity was found in the visual network in FTF compared to FTR. In the FTF, significant positive correlations were found between GABA and functional connectivity of the ACC.
CONCLUSIONS: Our findings highlight the importance of ACC GABA levels, and functional connectivity of the ACC, in modulating antipsychotic drug response in schizophrenia patients. Furthermore, the positive correlation of GABA and functional connectivity in FTF patients suggest that the function of GABA may be altered in some respects from an inhibitory to a facilitating neurochemistry in non-responding schizophrenic patients. Whether supplementation with GABA or GABA receptor agonists could improve clinical response further investigation in future studies.
PMID:42762746 | DOI:10.1016/j.schres.2026.09.014
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