4.2 Striatal Glutamate as Biomarker of Clinical Response to First-Line Treatment in Antipsychotic-naïve, First-Episode Psychosis Patients
Bibliographic record
Abstract
Background: Glutamate level in the precommissural dorsal caudate (i.e., associative striatum) is increased in antipsychotic-naive patients with first-episode psychosis (FEP). This increase normalizes after effective clinical response to first-line antipsychotic treatment. However, it is unclear if glutamate level is different between FEP resistant and responsive to first-line treatment and if glutamate could assist as a biomarker to predict treatment response. Methods: Forty-eight antipsychotic-naive FEP patients were studied. Patients were treated open label with risperidone, with doses adjusted based on clinical judgment. Response was defined as a reduction of 40% or more in the PANSS positive symptom subscale after 4 weeks of treatment. 1H-MRS scans were obtained from the right precomissural dorsal-caudate (TE = 35 ms) at baseline prior to start of treatment and after 4 weeks of treatment. Glutamate levels were estimated using LC Model and corrected for the cerebrospinal fluid proportion within the voxel. Results: After 4 weeks of treatment, 29 patients responded to treatment and 19 did not. At the baseline scan, patients assigned as resistant showed trend-level glutamate elevations compared to responders (P = .07). In the 4-week scan, resistant patients showed higher levels of glutamate compared to responders (P = .02). Conclusion: Our results support that striatal glutamate is higher in FEP patients that are resistant to first-line treatment in comparison to responsive patients. In addition, our results suggest that baseline striatal glutamate level could predict treatment response. These results should be confirmed with a larger sample, different first-line antipsychotics, and during a second treatment trial of first-line antipsychotic.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.042 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".