Neuroimaging glutamatergic mechanisms differentiating antipsychotic treatment-response
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 c...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-26702-0 |
| _version_ | 1797778909861773312 |
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| author | Elias D. Mouchlianitis Lucy D. Vanes Derek K. Tracy Anne-Kathrin Fett Daniel Joyce Sukhi S. Shergill |
| author_facet | Elias D. Mouchlianitis Lucy D. Vanes Derek K. Tracy Anne-Kathrin Fett Daniel Joyce Sukhi S. Shergill |
| author_sort | Elias D. Mouchlianitis |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T23:23:20Z |
| format | Article |
| id | doaj.art-776f54c724f748f79727a39c8d72a0b9 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T23:23:20Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-776f54c724f748f79727a39c8d72a0b92023-07-16T11:17:16ZengNature PortfolioScientific Reports2045-23222023-06-0113111010.1038/s41598-022-26702-0Neuroimaging glutamatergic mechanisms differentiating antipsychotic treatment-responseElias D. Mouchlianitis0Lucy D. Vanes1Derek K. Tracy2Anne-Kathrin Fett3Daniel Joyce4Sukhi S. Shergill5Institute of Psychiatry, Psychology and NeuroscienceInstitute of Psychiatry, Psychology and NeuroscienceInstitute of Psychiatry, Psychology and NeuroscienceInstitute of Psychiatry, Psychology and NeuroscienceInstitute of Psychiatry, Psychology and NeuroscienceInstitute of Psychiatry, Psychology and NeuroscienceAbstract 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.https://doi.org/10.1038/s41598-022-26702-0 |
| spellingShingle | Elias D. Mouchlianitis Lucy D. Vanes Derek K. Tracy Anne-Kathrin Fett Daniel Joyce Sukhi S. Shergill Neuroimaging glutamatergic mechanisms differentiating antipsychotic treatment-response Scientific Reports |
| title | Neuroimaging glutamatergic mechanisms differentiating antipsychotic treatment-response |
| title_full | Neuroimaging glutamatergic mechanisms differentiating antipsychotic treatment-response |
| title_fullStr | Neuroimaging glutamatergic mechanisms differentiating antipsychotic treatment-response |
| title_full_unstemmed | Neuroimaging glutamatergic mechanisms differentiating antipsychotic treatment-response |
| title_short | Neuroimaging glutamatergic mechanisms differentiating antipsychotic treatment-response |
| title_sort | neuroimaging glutamatergic mechanisms differentiating antipsychotic treatment response |
| url | https://doi.org/10.1038/s41598-022-26702-0 |
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