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.