Abstract
Glutamatergic dysfunction is associated with failure to respond to antipsychotic medication in individuals with schizophrenia. Our objective was to combine neurochemical and functional brain imaging methods to investigate glutamatergic dysfunction and reward processing in such individuals compared with those with treatment responsive schizophrenia, and healthy controls. 60 participants played a trust task, while undergoing functional magnetic resonance imaging: 21 classified as having treatment-resistant schizophrenia, 21 patients with treatment-responsive schizophrenia, and 18 healthy controls. Proton magnetic resonance spectroscopy was also acquired to measure glutamate in the anterior cingulate cortex. Compared to controls, treatment responsive and treatment-resistant participants showed reduced investments during the trust task. For treatment-resistant individuals, glutamate levels in the anterior cingulate cortex were associated with signal decreases in the right dorsolateral prefrontal cortex when compared to those treatment-responsive, and with bilateral dorsolateral prefrontal cortex and left parietal association cortex when compared to controls. Treatment-responsive participants showed significant signal decreases in the anterior caudate compared to the other two groups. Our results provide evidence that glutamatergic differences differentiate treatment resistant and responsive schizophrenia. The differentiation of cortical and sub-cortical reward learning substrates has potential diagnostic value. Future novel interventions might therapeutically target neurotransmitters affecting the cortical substrates of the reward network.
| Original language | English |
|---|---|
| Article number | 8938 |
| Pages (from-to) | 1-10 |
| Number of pages | 10 |
| Journal | Scientific Reports |
| Volume | 13 |
| DOIs | |
| Publication status | Published - 2 Jun 2023 |
Bibliographical note
Funding Information:We thank the radiographic team at the Centre for Neuroimaging Sciences for their support, and Felix Dransfield, Christiana Ilesanmi, Valentina Forassi and Juliet Gillam for assistance with fMRI scanning and behavioral testing. This research was funded by a European Research Council Grant to SSS (grant number 311686), and developed by the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London and a joint infrastructure grant from Guy's and St Thomas' Charity and the Maudsley Charity. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Publisher Copyright:
© 2023, The Author(s).
Funding
We thank the radiographic team at the Centre for Neuroimaging Sciences for their support, and Felix Dransfield, Christiana Ilesanmi, Valentina Forassi and Juliet Gillam for assistance with fMRI scanning and behavioral testing. This research was funded by a European Research Council Grant to SSS (grant number 311686), and developed by the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London and a joint infrastructure grant from Guy's and St Thomas' Charity and the Maudsley Charity. The data that support the findings of this study are available from the corresponding author upon reasonable request.