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Interactions between hippocampal activity and striatal dopamine in people at clinical high risk for psychosis: relationship to adverse outcomes
journal contribution
posted on 2023-06-10, 00:53 authored by Gemma Modinos, Anja Richter, Alice Egerton, Ilaria Bonoldi, Matilda Azis, Mathilde Antoniades, Matthijs Bossong, Nicolas Crossley, Jesus Perez, James StoneJames Stone, Mattia Veronese, Fernando Zelaya, Anthony A Grace, Oliver D Howes, Paul Allen, Philip McGuirePreclinical models propose that increased hippocampal activity drives subcortical dopaminergic dysfunction and leads to psychosis-like symptoms and behaviors. Here, we used multimodal neuroimaging to examine the relationship between hippocampal regional cerebral blood flow (rCBF) and striatal dopamine synthesis capacity in people at clinical high risk (CHR) for psychosis and investigated its association with subsequent clinical and functional outcomes. Ninety-five participants (67 CHR and 28 healthy controls) underwent arterial spin labeling MRI and 18F-DOPA PET imaging at baseline. CHR participants were followed up for a median of 15 months to determine functional outcomes with the global assessment of function (GAF) scale and clinical outcomes using the comprehensive assessment of at-risk mental states (CAARMS). CHR participants with poor functional outcomes (follow-up GAF < 65, n = 25) showed higher rCBF in the right hippocampus compared to CHRs with good functional outcomes (GAF = 65, n = 25) (pfwe = 0.026). The relationship between rCBF in this right hippocampal region and striatal dopamine synthesis capacity was also significantly different between groups (pfwe = 0.035); the association was negative in CHR with poor outcomes (pfwe = 0.012), but non-significant in CHR with good outcomes. Furthermore, the correlation between right hippocampal rCBF and striatal dopamine function predicted a longitudinal increase in the severity of positive psychotic symptoms within the total CHR group (p = 0.041). There were no differences in rCBF, dopamine, or their associations in the total CHR group relative to controls. These findings indicate that altered interactions between the hippocampus and the subcortical dopamine system are implicated in the pathophysiology of adverse outcomes in the CHR state.
History
Publication status
- Published
File Version
- Published version
Journal
NeuropsychopharmacologyISSN
0893-133XPublisher
Springer NatureExternal DOI
Volume
46Page range
1468-1474Event location
EnglandDepartment affiliated with
- BSMS Neuroscience Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-09-09First Open Access (FOA) Date
2021-09-09First Compliant Deposit (FCD) Date
2021-09-09Usage metrics
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