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Connectome dysfunction in patients at clinical high risk for psychosis and modulation by oxytocin

Davies, Cathy, Martins, Daniel, Dipasquale, Ottavia, McCutcheon, Robert A, De Micheli, Andrea, Ramella-Cravaro, Valentina, Provenzani, Umberto, Rutigliano, Grazia, Cappucciati, Marco, Oliver, Dominic, and others. (2024) Connectome dysfunction in patients at clinical high risk for psychosis and modulation by oxytocin. Molecular Psychiatry, . ISSN 1476-5578. (doi:10.1038/s41380-024-02406-x) (KAR id:104840)


Abnormalities in functional brain networks (functional connectome) are increasingly implicated in people at Clinical High Risk for Psychosis (CHR-P). Intranasal oxytocin, a potential novel treatment for the CHR-P state, modulates network topology in healthy individuals. However, its connectomic effects in people at CHR-P remain unknown. Forty-seven men (30 CHR-P and 17 healthy controls) received acute challenges of both intranasal oxytocin 40 IU and placebo in two parallel randomised, double-blind, placebo-controlled cross-over studies which had similar but not identical designs. Multi-echo resting-state fMRI data was acquired at approximately 1 h post-dosing. Using a graph theoretical approach, the effects of group (CHR-P vs healthy control), treatment (oxytocin vs placebo) and respective interactions were tested on graph metrics describing the topology of the functional connectome. Group effects were observed in 12 regions (all p  < 0.05) most localised to the frontoparietal network. Treatment effects were found in 7 regions (all p  < 0.05) predominantly within the ventral attention network. Our major finding was that many effects of oxytocin on network topology differ across CHR-P and healthy individuals, with significant interaction effects observed in numerous subcortical regions strongly implicated in psychosis onset, such as the thalamus, pallidum and nucleus accumbens, and cortical regions which localised primarily to the default mode network (12 regions, all p  < 0.05). Collectively, our findings provide new insights on aberrant functional brain network organisation associated with psychosis risk and demonstrate, for the first time, that oxytocin modulates network topology in brain regions implicated in the pathophysiology of psychosis in a clinical status (CHR-P vs healthy control) specific manner.

Item Type: Article
DOI/Identification number: 10.1038/s41380-024-02406-x
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.
Subjects: R Medicine
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Funders: National Institute for Health Research (
Wellcome Trust (
Economic and Social Research Council (
SWORD Depositor: JISC Publications Router
Depositing User: JISC Publications Router
Date Deposited: 02 Feb 2024 15:05 UTC
Last Modified: 27 Feb 2024 11:31 UTC
Resource URI: (The current URI for this page, for reference purposes)

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