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

TY - JOUR

T1 - Connectome dysfunction in patients at clinical high risk for psychosis and modulation by oxytocin

AU - Davies, Cathy

AU - Martins, Daniel

AU - Dipasquale, Ottavia

AU - McCutcheon, Robert A.

AU - De Micheli, Andrea

AU - Ramella-Cravaro, Valentina

AU - Provenzani, Umberto

AU - Rutigliano, Grazia

AU - Cappucciati, Marco

AU - Oliver, Dominic

AU - Williams, Steven

AU - Zelaya, Fernando

AU - Allen, Paul

AU - Murguia, Silvia

AU - Taylor, David

AU - Shergill, Sukhi

AU - Morrison, Paul

AU - McGuire, Philip

AU - Paloyelis, Yannis

AU - Fusar-Poli, Paolo

AU - Martins, Daniel

N1 - Funding Information: This work was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London (PFP, PMc, YP, DM); by a Brain & Behaviour Research Foundation NARSAD Award (grant number 22593 to PFP); an Economic and Social Research Council Grant (ES/K009400/1 to YP); by an unrestricted research grant by PARI GmbH to YP; and by the Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London. RAM’s work was supported by a NIHR Clinical Lectureship and a Wellcome Trust Clinical Research Career Development Fellowship. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The funders had no influence on the design, collection, analysis and interpretation of the data, writing of the report and decision to submit this article for publication. Publisher Copyright: © 2024, The Author(s).

PY - 2024/1/19

Y1 - 2024/1/19

N2 - 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 FDR < 0.05) most localised to the frontoparietal network. Treatment effects were found in 7 regions (all p FDR < 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 FDR < 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.

AB - 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 FDR < 0.05) most localised to the frontoparietal network. Treatment effects were found in 7 regions (all p FDR < 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 FDR < 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.

KW - Graph Theory

KW - Oxytocin

KW - Clinical High Risk for Psychosis

KW - Connectivity

UR - http://www.scopus.com/inward/record.url?scp=85182704897&partnerID=8YFLogxK

U2 - 10.1038/s41380-024-02406-x

DO - 10.1038/s41380-024-02406-x

M3 - Article

SN - 1359-4184

VL - 29

SP - 1241

EP - 1252

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 5

ER -