Assessing plasma and brain glutamate in treatment resistant and non-resistant schizophrenia: a peripheral-central disconnect.

BACKGROUND

The role of peripheral glutamate as an accessible biomarker for schizophrenia remains unclear. Its potential to reflect illness progression or differentiate treatment-resistant (TRS) from non-resistant (non-TRS) patients, and its relationship with central glutamate, require further investigation. This exploratory study assessed plasma glutamate levels and their associations with anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) glutamate in both TRS and non-TRS patients. Additionally, we examined associations between plasma glutamate and clinical characteristics, including psychiatric and cognitive measures.

METHODS

We examined 71 patients (33 non-TRS, 38 TRS). Plasma glutamate was measured using colorimetry, and ACC and mPFC glutamate were assessed via Magnetic Resonance Spectroscopy (MRS).

RESULTS

Plasma glutamate levels were significantly higher in non-TRS compared to TRS patients. However, there was no significant correlation between plasma glutamate and ACC or mPFC glutamate in either group. Furthermore, plasma glutamate was not associated with clinical measures, including Positive and Negative Syndrome Scale (PANSS) scores, aggression scores, general scores, or the working memory index.

CONCLUSION

There is preliminary evidence that peripheral glutamate levels are lower in TRS compared to non-TRS patients; however, peripheral glutamate does not appear to reliably reflect brain glutamate levels or symptom severity in schizophrenia.