title: Progressive Decline in Hippocampal CA1 Volume in Individuals at Ultra-High-Risk for Psychosis Who Do Not Remit: Findings from the Longitudinal Youth at Risk Study.
abstract: Most individuals identified as ultra-high-risk (UHR) for psychosis do not develop frank psychosis. They continue to exhibit subthreshold symptoms, or go on to fully remit. Prior work has shown that the volume of CA1, a subfield of the hippocampus, is selectively reduced in the early stages of schizophrenia. Here we aimed to determine whether patterns of volume change of CA1 are different in UHR individuals who do or do not achieve symptomatic remission. Structural MRI scans were acquired at baseline and at 1-2 follow-up time points (at 12-month intervals) from 147 UHR and healthy control subjects. An automated method (based on an ex vivo atlas of ultra-high-resolution hippocampal tissue) was used to delineate the hippocampal subfields. Over time, a greater decline in bilateral CA1 subfield volumes was found in the subgroup of UHR subjects whose subthreshold symptoms persisted (n=40) and also those who developed clinical psychosis (n=12), compared with UHR subjects who remitted (n=41) and healthy controls (n=54). No baseline differences in volumes of the overall hippocampus or its subfields were found among the groups. Moreover, the rate of volume decline of CA1, but not of other hippocampal subfields, in the non-remitters was associated with increasing symptom severity over time. Thus, these findings indicate that there is deterioration of CA1 volume in persistently symptomatic UHR individuals in proportion to symptomatic progression.
authors.affiliation: Institute of Mental Health, Singapore, Singapore.|Neuroscience and Behavioral Disorders Program, Center for Cognitive Neuroscience, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
authors.forename: New Fei
authors.identifier: http://orcid.org/0000-0002-0456-3391
authors.initials: NF
authors.lastname: Ho
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Daphne J
authors.initials: DJ
authors.lastname: Holt
authors.affiliation: Department of Psychology, National University of Singapore, Singapore, Singapore.
authors.forename: Mike
authors.initials: M
authors.lastname: Cheung
authors.affiliation: University College London, London, UK.
authors.forename: Juan Eugenio
authors.initials: JE
authors.lastname: Iglesias
authors.affiliation: Institute of Mental Health, Singapore, Singapore.
authors.forename: Alex
authors.initials: A
authors.lastname: Goh
authors.affiliation: Institute of Mental Health, Singapore, Singapore.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Wang
authors.affiliation: Neuroscience and Behavioral Disorders Program, Center for Cognitive Neuroscience, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
authors.forename: Joseph Kw
authors.initials: JK
authors.lastname: Lim
authors.affiliation: Neuroscience and Behavioral Disorders Program, Center for Cognitive Neuroscience, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
authors.forename: Joshua
authors.initials: J
authors.lastname: de Souza
authors.affiliation: Neuroscience and Behavioral Disorders Program, Center for Cognitive Neuroscience, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
authors.forename: Joann S
authors.identifier: http://orcid.org/0000-0002-4484-9028
authors.initials: JS
authors.lastname: Poh
authors.affiliation: Institute of Mental Health, Singapore, Singapore.
authors.forename: Yuen Mei
authors.initials: YM
authors.lastname: See
authors.affiliation: Center for Cognitive Neuroscience, Duke University, Durham, NC, USA.
authors.forename: Alison R
authors.initials: AR
authors.lastname: Adcock
authors.affiliation: School of Psychology, University of Birmingham, Birmingham, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Wood
authors.affiliation: Neuroscience and Behavioral Disorders Program, Center for Cognitive Neuroscience, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
authors.forename: Michael Wl
authors.identifier: http://orcid.org/0000-0002-6087-0548
authors.initials: MW
authors.lastname: Chee
authors.affiliation: Institute of Mental Health, Singapore, Singapore.
authors.forename: Jimmy
authors.identifier: http://orcid.org/0000-0002-7724-7445
authors.initials: J
authors.lastname: Lee
authors.affiliation: Neuroscience and Behavioral Disorders Program, Center for Cognitive Neuroscience, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D056547:CA1 Region, Hippocampal / Q000000981:diagnostic imaging / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D062706:Prodromal Symptoms; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D012306:Risk; D012720:Severity of Illness Index; D055815:Young Adult