title: Neuroanatomical Predictors of Functional Outcome in Individuals at Ultra-High Risk for Psychosis.
abstract: Most individuals at ultra-high risk (UHR) for psychosis do not transition to frank illness. Nevertheless, many have poor clinical outcomes and impaired psychosocial functioning. This study used voxel-based morphometry to investigate if baseline grey and white matter brain densities at identification as UHR were associated with functional outcome at medium- to long-term follow-up. Participants were help-seeking UHR individuals (n = 109, 54M:55F) who underwent magnetic resonance imaging at baseline; functional outcome was assessed an average of 9.2 years later. Primary analysis showed that lower baseline grey matter density, but not white matter density, in bilateral frontal and limbic areas, and left cerebellar declive were associated with poorer functional outcome (Social and Occupational Functioning Assessment Scale [SOFAS]). These findings were independent of transition to psychosis or persistence of the at-risk mental state. Similar regions were significantly associated with lower self-reported levels of social functioning and increased negative symptoms at follow-up. Exploratory analyses showed that lower baseline grey matter densities in middle and inferior frontal gyri were significantly associated with decline in Global Assessment of Functioning (GAF) score over follow-up. There was no association between baseline grey matter density and IQ or positive symptoms at follow-up. The current findings provide novel evidence that those with the poorest functional outcomes have the lowest grey matter densities at identification as UHR, regardless of transition status or persistence of the at-risk mental state. Replication and validation of these findings may allow for early identification of poor functional outcome and targeted interventions.
authors.affiliation: School of Psychology, University of Birmingham, Birmingham, UK.
authors.forename: Renate L E P
authors.initials: RL
authors.lastname: Reniers
authors.affiliation: Telethon Kids Institute, The University of Western Australia, Perth, Australia.
authors.forename: Ashleigh
authors.initials: A
authors.lastname: Lin
authors.affiliation: Institute of Brain Behaviour and Mental Health, University of Manchester, Manchester, UK.
authors.forename: Alison R
authors.initials: AR
authors.lastname: Yung
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University of Munich, Munich, Germany.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Koutsouleris
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Melbourne, Australia.
authors.forename: Barnaby
authors.initials: B
authors.lastname: Nelson
authors.affiliation: Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Melbourne, Australia.
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Cropley
authors.affiliation: Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Melbourne, Australia.
authors.forename: Dennis
authors.initials: D
authors.lastname: Velakoulis
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Melbourne, Australia.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: McGorry
authors.affiliation: Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Melbourne, Australia.|Centre for Neural Engineering, Department of Electrical and Electronic Engineering, University of Melbourne, Victoria, Australia.|Florey Institute for Neuroscience & Mental Health, Victoria, Australia.
authors.forename: Christos
authors.initials: C
authors.lastname: Pantelis
authors.affiliation: School of Psychology, University of Birmingham, Birmingham, UK.|Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Melbourne, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Wood
mesh_terms: D000293:Adolescent; D000328:Adult; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000000981:diagnostic imaging*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D017063:Outcome Assessment, Health Care; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging*; D011618:Psychotic Disorders / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D012306:Risk; D066127:White Matter / Q000000981:diagnostic imaging; D055815:Young Adult
keywords: clinical high risk; functional outcome; grey matter density; negative symptoms; psychosis; ultra-high risk; voxel-based morphometry