title: Progressive reduction in cortical thickness as psychosis develops: a multisite longitudinal neuroimaging study of youth at elevated clinical risk.
abstract: BACKGROUND
  Individuals at clinical high risk (CHR) who progress to fully psychotic symptoms have been observed to show a steeper rate of cortical gray matter reduction compared with individuals without symptomatic progression and with healthy control subjects. Whether such changes reflect processes associated with the pathophysiology of schizophrenia or exposure to antipsychotic drugs is unknown.
  
  
  METHODS
  In this multisite study, 274 CHR cases, including 35 individuals who converted to psychosis, and 135 healthy comparison subjects were scanned with magnetic resonance imaging at baseline, 12-month follow-up, or the point of conversion for the subjects who developed fully psychotic symptoms.
  
  
  RESULTS
  In a traveling subjects substudy, excellent reliability was observed for measures of cortical thickness and subcortical volumes. Controlling for multiple comparisons throughout the brain, CHR subjects who converted to psychosis showed a steeper rate of gray matter loss in the right superior frontal, middle frontal, and medial orbitofrontal cortical regions as well as a greater rate of expansion of the third ventricle compared with CHR subjects who did not convert to psychosis and healthy control subjects. Differential tissue loss was present in subjects who had not received antipsychotic medications during the interscan interval and was predicted by baseline levels of an aggregate measure of proinflammatory cytokines in plasma.
  
  
  CONCLUSIONS
  These findings demonstrate that the brain changes are not explained by exposure to antipsychotic drugs but likely play a role in psychosis pathophysiology. Given that the cortical changes were more pronounced in subjects with briefer durations of prodromal symptoms, contributing factors may predominantly play a role in acute-onset forms of psychosis.
authors.affiliation: Departments of Psychology, Yale University, New Haven, Connecticut; Departments of Psychiatry, Yale University, New Haven, Connecticut. Electronic address: tyrone.cannon@yale.edu.
authors.forename: Tyrone D
authors.initials: TD
authors.lastname: Cannon
authors.affiliation: Departments of Psychology, Yale University, New Haven, Connecticut.
authors.forename: Yoonho
authors.initials: Y
authors.lastname: Chung
authors.affiliation: Departments of Psychology, Yale University, New Haven, Connecticut.
authors.forename: George
authors.initials: G
authors.lastname: He
authors.affiliation: Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California, Los Angeles, Los Angeles, California.
authors.forename: Daqiang
authors.initials: D
authors.lastname: Sun
authors.affiliation: Departments of Psychology, Yale University, New Haven, Connecticut.
authors.forename: Aron
authors.initials: A
authors.lastname: Jacobson
authors.affiliation: Department of Psychiatry, University of California, Irvine, Irvine, California.
authors.forename: Theo G M
authors.initials: TG
authors.lastname: van Erp
authors.affiliation: Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California, Los Angeles, Los Angeles, California.
authors.forename: Sarah
authors.initials: S
authors.lastname: McEwen
authors.affiliation: Department of Psychiatry (JA), University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Addington
authors.affiliation: Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California, Los Angeles, Los Angeles, California.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Bearden
authors.affiliation: Department of Psychiatry, University of California, San Diego, San Diego, California.
authors.forename: Kristin
authors.initials: K
authors.lastname: Cadenhead
authors.affiliation: Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cornblatt
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, California.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Mathalon
authors.affiliation: Departments of Psychiatry, Yale University, New Haven, Connecticut.
authors.forename: Thomas
authors.initials: T
authors.lastname: McGlashan
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Diana
authors.initials: D
authors.lastname: Perkins
authors.affiliation: Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Clark
authors.initials: C
authors.lastname: Jeffries
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.affiliation: Department of Psychiatry, University of California, San Diego, San Diego, California.
authors.forename: Ming
authors.initials: M
authors.lastname: Tsuang
authors.affiliation: Department of Psychology, Emory University, Atlanta, Georgia.
authors.forename: Elaine
authors.initials: E
authors.lastname: Walker
authors.affiliation: Departments of Psychiatry, Yale University, New Haven, Connecticut.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Woods
authors.affiliation: Division of Treatment and Prevention Research, National Institute of Mental Health, Rockville, Maryland.
authors.forename: Robert
authors.initials: R
authors.lastname: Heinssen
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology*; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D062706:Prodromal Symptoms; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D015203:Reproducibility of Results; D012306:Risk; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D016207:Cytokines
keywords: Inflammation; MRI; Prefrontal cortex; Prodromal; Psychosis; Schizophrenia