The association among glutamate, GABA, and anterior cingulate connectivity in schizophrenia spectrum disorders: Implications for symptom domains.

BACKGROUND

Schizophrenia-spectrum disorders (SSD) are characterized by structural and functional brain abnormalities, including disrupted functional connectivity within networks such as the salience network. The anterior cingulate cortex (ACC), a core hub of this network, has shown alterations in the major neurotransmitter systems comprising glutamate (Glu) and γ-aminobutyric acid (GABA). While dysfunctional glutamatergic signaling has been proposed as a key mechanism in SSDs, the relationship between anterior cingulate cortex (ACC) functional connectivity, glutamatergic neurotransmission, and clinical symptomatology remains poorly understood.

METHODS

Here, we combined resting-state functional MRI to measure functional brain connectivity with proton magnetic resonance spectroscopy to measure Glu and GABA levels in the dorsal ACC of 26 patients with schizophrenia spectrum disorders and 38 healthy controls.

RESULTS

Patients showed reduced connectivity within the salience network compared to controls. Across the whole sample, a dorsal ACC-seed showed glutamate-dependent connectivity to several clusters, including right insula, thalamus, and cerebellum. In patients, the averaged connectivity of these clusters was associated with positive symptom severity.

CONCLUSIONS

These findings suggest that disrupted glutamatergic modulation of large-scale brain networks may underlie core clinical features in schizophrenia spectrum disorders.