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

• DOI: 10.1101/2023.03.17.23286528
• Publication Date: 2023-03-21T15:45:24Z
• Authors: Cathy Davies; Daniel Martins; Ottavia Dipasquale; Robert A. McCutcheon; Andrea De Micheli; Valentina Ramella...; Umberto Provenzani; Grazia Rutigliano; Marco Cappucciati; Dominic Oliver; Steve Williams; Fernando Zelaya; Paul Allen; Silvia Murguia; David Taylor; Sukhi Shergill; Paul Morrison; Philip McGuire; Yannis Paloyelis; Paolo Fusar-Poli
• Keywords: Male; Adult; Risk; Connectivity; Cross-Over Studies; Adolescent; 610; Brain; Clinical High Risk for Psychosis; Oxytocin; Magnetic Resonance Imaging; Article; 3. Good health; Young Adult; Psychotic Disorders; Double-Blind Method; Graph Theory; 616; Connectome; Humans; Nerve Net; Administration, Intranasal

ABSTRACT Abnormalities in functional brain networks (functional connectome) are increasingly implicated people at Clinical High Risk for Psychosis (CHR-P). Intranasal oxytocin, a potential novel treatment the CHR-P state, modulates network topology healthy individuals. However, its connectomic effects remain unknown. Forty-seven men (30 and 17 controls) received acute challenges of both intranasal oxytocin 40 IU placebo two parallel randomised, double-blind, placebo-controlled cross-over studies. Multi-echo resting-state fMRI data was acquired approximately 1h post-dosing. Using graph theoretical approach, group (CHR-P vs control), (oxytocin placebo) respective interactions were tested on metrics describing connectome. Group observed 12 regions (all p FDR <.05) most localised to frontoparietal network. Treatment found 7 predominantly within ventral attention Our major finding that many differ across individuals, with significant interaction numerous subcortical strongly psychosis onset, such as thalamus, pallidum nucleus accumbens, cortical which primarily default mode (12 regions, all <.05). findings provide new insights aberrant organisation associated risk demonstrate, first time, pathophysiology clinical status control) specific manner. Further profiling connectomic, cognitive this population is warranted.