Interactions between hippocampal activity and striatal dopamine in people at clinical high risk for psychosis: relationship to adverse outcomes

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dc.catalogadorgrr
dc.contributor.authorModinos, Gemma
dc.contributor.authorRichter, Anja
dc.contributor.authorEgerton, Alice
dc.contributor.authorBonoldi. Ilaria
dc.contributor.authorAzis, Matilda
dc.contributor.authorAntoniades, Mathilde
dc.contributor.authorBossong, Matthijs
dc.contributor.authorCrossley Karmelic, Nicolas Andres
dc.contributor.authorPerez, Jesus
dc.contributor.authorStone, James M.
dc.contributor.authorVeronese, Mattia
dc.contributor.authorZelaya, Fernando
dc.contributor.authorGrace, Anthony A.
dc.contributor.authorHowes, Oliver D.
dc.contributor.authorAllen, Paul
dc.contributor.authorMcGuire, Phillip
dc.date.accessioned2024-06-04T15:54:37Z
dc.date.available2024-06-04T15:54:37Z
dc.date.issued2021
dc.description.abstractPreclinical 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.
dc.fechaingreso.objetodigital2024-06-04
dc.format.extent7 páginas
dc.fuente.origenScopus
dc.identifier.doi10.1038/s41386-021-01019-0
dc.identifier.eissn1740634X
dc.identifier.issn0893-133X
dc.identifier.pubmedid33941857
dc.identifier.scopusidSCOPUS_ID:85105298891
dc.identifier.urihttps://doi.org/10.1038/s41386-021-01019-0
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/86388
dc.identifier.wosidWOS:000646512900005
dc.information.autorucEscuela de Medicina; Crossley Karmelic, Nicolas Andres; 0000-0002-3060-656X; 11224
dc.issue.numero8
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final1474
dc.pagina.inicio1468
dc.publisherSpringer Nature
dc.revistaNeuropsychopharmacology
dc.rightsacceso abierto
dc.rights.license CC BY 4.0 DEED Atribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.en
dc.subject610
dc.titleInteractions between hippocampal activity and striatal dopamine in people at clinical high risk for psychosis: relationship to adverse outcomes
dc.typeartículo
dc.volumen46
sipa.codpersvinculados11224
sipa.trazabilidadScopus;12-10-2021
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