title: Structural Network Disorganization in Subjects at Clinical High Risk for Psychosis.
abstract: Previous network studies in chronic schizophrenia patients revealed impaired structural organization of the brain's rich-club members, a set of highly interconnected hub regions that play an important integrative role for global brain communication. Moreover, impaired rich-club connectivity has also been found in unaffected siblings of schizophrenia patients, suggesting that abnormal rich-club connectivity is related to familiar, possibly reflecting genetic, vulnerability for schizophrenia. However, no study has yet investigated whether structural rich-club organization is also impaired in individuals with a clinical risk syndrome for psychosis. Diffusion tensor imaging and probabilistic tractography was used to construct structural whole-brain networks in 24 healthy controls and 24 subjects with an at-risk mental state (ARMS). Graph theory was applied to quantify the structural rich-club organization and global network properties. ARMS subjects revealed a significantly altered structural rich-club organization compared with the control group. The disruption of rich-club organization was associated with the severity of negative psychotic symptoms and led to an elevated level of modularity in ARMS subjects. This study shows that abnormal structural rich-club organization is already evident in clinical high-risk subjects for psychosis and further demonstrates the impact of rich-club disorganization on global network communication. Together with previous evidence in chronic schizophrenia patients and unaffected siblings, our findings suggest that abnormal structural rich-club organization may reflect an endophenotypic marker of psychosis.
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology and Neuroscience, PO63 De Crespigny Park, London, UK.
authors.forename: André
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology and Neuroscience, PO63 De Crespigny Park, London, UK.
authors.forename: Nicolas A
authors.initials: NA
authors.lastname: Crossley
authors.affiliation: Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Harrisberger
authors.affiliation: Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
authors.forename: Renata
authors.initials: R
authors.lastname: Smieskova
authors.affiliation: Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Lenz
authors.affiliation: Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
authors.forename: Anita
authors.initials: A
authors.lastname: Riecher-Rössler
authors.affiliation: Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
authors.forename: Undine E
authors.initials: UE
authors.lastname: Lang
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology and Neuroscience, PO63 De Crespigny Park, London, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: McGuire
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology and Neuroscience, PO63 De Crespigny Park, London, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fusar-Poli
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology and Neuroscience, PO63 De Crespigny Park, London, UK.|Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Borgwardt
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000000981:diagnostic imaging*; D011618:Psychotic Disorders / Q000000981:diagnostic imaging* / Q000503:physiopathology; D012306:Risk; D012720:Severity of Illness Index; D055815:Young Adult
keywords: clinical high risk; graph theory; network; psychosis; rich-club; structural connectivity