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

Autor: Davies C; Early Psychosis: Interventions & Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. cathy.davies@kcl.ac.uk.; Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. cathy.davies@kcl.ac.uk.; Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. cathy.davies@kcl.ac.uk., Martins D; Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.; National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre (BRC), South London and Maudsley NHS Foundation Trust, London, UK.; Department of Psychiatry, University Hospitals of Genève, Geneva, Switzerland., Dipasquale O; Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK., McCutcheon RA; Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.; Department of Psychiatry, University of Oxford, Oxford, UK., De Micheli A; Early Psychosis: Interventions & Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.; Outreach And Support in South London (OASIS) Service, South London and Maudsley NHS Foundation Trust, London, UK., Ramella-Cravaro V; Early Psychosis: Interventions & Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK., Provenzani U; Early Psychosis: Interventions & Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy., Rutigliano G; Early Psychosis: Interventions & Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK., Cappucciati M; Early Psychosis: Interventions & Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK., Oliver D; Early Psychosis: Interventions & Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.; Department of Psychiatry, University of Oxford, Oxford, UK., Williams S; Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK., Zelaya F; Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK., Allen P; Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK., Murguia S; Tower Hamlets Early Detection Service, East London NHS Foundation Trust, London, UK., Taylor D; Institute of Pharmaceutical Science, King's College London, London, UK., Shergill S; Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.; Kent and Medway Medical School, Canterbury, UK., Morrison P; Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK., McGuire P; Department of Psychiatry, University of Oxford, Oxford, UK.; NIHR Oxford Health Biomedical Research Centre, Oxford, UK.; Oxford Health NHS Foundation Trust, Oxford, UK., Paloyelis Y; Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK., Fusar-Poli P; Early Psychosis: Interventions & Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.; National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre (BRC), South London and Maudsley NHS Foundation Trust, London, UK.; Outreach And Support in South London (OASIS) Service, South London and Maudsley NHS Foundation Trust, London, UK.; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 May; Vol. 29 (5), pp. 1241-1252. Date of Electronic Publication: 2024 Jan 19.
DOI: 10.1038/s41380-024-02406-x
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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