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Neuroimaging glutamatergic mechanisms differentiating antipsychotic treatment-response

Mouchlianitis, Elias D., Vanes, Lucy D., Tracy, Derek K., Fett, Anne-Katherin, Joyce, Daniel, Shergill, Sukhi S. (2023) Neuroimaging glutamatergic mechanisms differentiating antipsychotic treatment-response. Scientific Reports, 13 (1). Article Number 8938. E-ISSN 2045-2322. (doi:10.1038/s41598-022-26702-0) (KAR id:101513)


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.

Item Type: Article
DOI/Identification number: 10.1038/s41598-022-26702-0
Additional information: For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Uncontrolled keywords: Neuroimaging, Humans, Antipsychotic Agents - pharmacology - therapeutic use, Prefrontal Cortex - diagnostic imaging, Magnetic Resonance Imaging, Gyrus Cinguli - diagnostic imaging - physiology, Glutamic Acid
Subjects: R Medicine > R Medicine (General)
Divisions: Divisions > Division of Natural Sciences > Kent and Medway Medical School
Funders: European Research Council (
SWORD Depositor: JISC Publications Router
Depositing User: JISC Publications Router
Date Deposited: 08 Jun 2023 14:23 UTC
Last Modified: 28 Jul 2023 14:35 UTC
Resource URI: (The current URI for this page, for reference purposes)

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