What glutamate connectivity associations are found in antipsychotic-naive first-episode psychosis individuals?
Glutamate is a key brain chemical that helps nerve cells communicate. In people with first-episode psychosis (FEP) who have never taken antipsychotic medication, researchers have found that glutamate levels in the anterior cingulate cortex (ACC) are linked to how different brain networks connect and talk to each other. These connections are often weaker or work differently than in healthy individuals, which may help explain some symptoms of psychosis.
What the research says
A 2024 study of 70 antipsychotic-naive FEP patients and 52 healthy controls measured glutamate+glutamine (Glx) in the dorsal anterior cingulate cortex (dACC) using magnetic resonance spectroscopy. They found that in FEP patients, the relationship between dACC Glx and functional connectivity in higher-order networks (default mode, dorsal attention, and executive control networks) was altered compared to controls. Specifically, the normal positive and negative associations between Glx and network connectivity were weaker or reversed in FEP 8. Another study from 2021 using the same sample found that in healthy controls, higher dACC Glx predicted stronger positive functional connectivity within the salience network (including the dACC and insula) and stronger negative connectivity in parietal regions. In FEP patients, these relationships were weaker or absent, suggesting that glutamate-driven salience network connectivity is disrupted early in psychosis 9. A related study in individuals at clinical high-risk for psychosis (CHR-P) also found a negative association between ACC Glx and functional connectivity between the nucleus accumbens and amygdala/hippocampus, indicating that glutamate-connectivity alterations may appear before full psychosis onset 5.
What to ask your doctor
- What do glutamate levels in the brain mean for my condition?
- How might altered brain connectivity affect my symptoms or treatment?
- Are there any treatments that target glutamate or brain connectivity?
- Should I consider any brain imaging studies as part of my care?
- What lifestyle changes might support brain health and connectivity?
This question is drawn from common patient questions about this topic and answered using cited medical research. We do not provide individualized advice.