title: Ventricular enlargement and progressive reduction of cortical gray matter are linked in prodromal youth who develop psychosis.
abstract: In a recent prospective longitudinal neuroimaging study, clinical high-risk (CHR) individuals who later developed full-blown psychosis showed an accelerated rate of gray matter thinning in superior and medial prefrontal cortex (PFC) and expansion of the ventricular system after applying a stringent correction for multiple comparisons. Although cortical and subcortical volume loss and enlarged ventricles are well characterized structural brain abnormalities among patients with schizophrenia, no prior study has evaluated whether these progressive changes of neuroanatomical indicators are linked in time prior to onset of psychosis. Therefore, we investigated the relationship between the changes in cortical gray matter thickness and ventricular volume using the longitudinal neuroimaging data from the North American Prodrome Longitudinal Study at the whole-brain level. The results showed that ventricular expansion is linked in time to progressive reduction of gray matter, rather than to structural changes in proximal subcortical regions, in a broadly distributed set of cortical regions among CHR youth, including superior, medial, lateral, and inferior PFC, superior temporal gyrus, and parietal cortices. In contrast, healthy controls did not show the same pattern of associations. The main findings were further replicated using a third assessment wave of MRI scans in a subset of study participants who were followed for an additional year. These findings suggest that the gray matter regions exhibiting aberrant rates of thinning in relation to psychosis risk are not limited to the PFC regions that survived the statistical threshold in our primary study, but also extend to other cortical regions previously implicated in schizophrenia.
authors.affiliation: Department of Psychology, Yale University, 2 Hillhouse Ave., New Haven, CT 06520-8205, United States.
authors.forename: Yoonho
authors.initials: Y
authors.lastname: Chung
authors.affiliation: Department of Psychiatry, Rush University Medical Center, 1750 W Harrison St, Jelke Ste 1425, Chicago, IL 60612, United States.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Haut
authors.affiliation: Department of Psychology, Yale University, 2 Hillhouse Ave., New Haven, CT 06520-8205, United States.
authors.forename: George
authors.initials: G
authors.lastname: He
authors.affiliation: Department of Psychiatry and Human Behavior, UC Irvine, 101 The City Drive, Irvine, CA 92697, United States.
authors.forename: Theo G M
authors.initials: TGM
authors.lastname: van Erp
authors.affiliation: Semel Institute for Neuroscience and Human Behavior and Department of Psychology, UCLA, 760 Westwood Plaza, Los Angeles, CA 90095, United States.
authors.forename: Sarah
authors.initials: S
authors.lastname: McEwen
authors.affiliation: Department of Psychiatry, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N4Z6, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Addington
authors.affiliation: Semel Institute for Neuroscience and Human Behavior and Department of Psychology, UCLA, 760 Westwood Plaza, Los Angeles, CA 90095, United States.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Bearden
authors.affiliation: Department of Psychiatry, UCSD, 9500 Gilman Drive, La Jolla, CA 92093-0761, United States.
authors.forename: Kristin
authors.initials: K
authors.lastname: Cadenhead
authors.affiliation: Department of Psychiatry, Zucker Hillside Hospital, 75-59 263rd St., Queens, NY 11004, United States.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cornblatt
authors.affiliation: Department of Psychiatry, UCSF, 401 Parnassus Avenue, San Francisco, CA 94143, United States.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Mathalon
authors.affiliation: Department of Psychiatry, Yale University, 300 George St., New Haven, CT 06511, United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: McGlashan
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, 101 Manning Dr, Chapel Hill, NC 27514, United States; Renaissance Computing Institute, University of North Carolina, Chapel Hill, United States.
authors.forename: Diana
authors.initials: D
authors.lastname: Perkins
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, 401 Park Drive, 2 East, Boston, MA 02215, United States; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, 401 Park Drive, 2 West, Boston, MA 02215, United States.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.affiliation: Department of Psychiatry, UCSD, 9500 Gilman Drive, La Jolla, CA 92093-0761, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Tsuang
authors.affiliation: Department of Psychology, Emory University, 487 Psychology Building, 36 Eagle Row, Atlanta, GA 30322, United States.
authors.forename: Elaine
authors.initials: E
authors.lastname: Walker
authors.affiliation: Department of Psychiatry, Yale University, 300 George St., New Haven, CT 06511, United States.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Woods
authors.affiliation: Department of Psychology, Yale University, 2 Hillhouse Ave., New Haven, CT 06520-8205, United States; Department of Psychiatry, Yale University, 300 George St., New Haven, CT 06511, United States. Electronic address: tyrone.cannon@yale.edu.
authors.forename: Tyrone D
authors.initials: TD
authors.lastname: Cannon
mesh_terms: D000293:Adolescent; D000328:Adult; D001929:Brain Edema / Q000000981:diagnostic imaging; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D002552:Cerebral Ventricles / Q000000981:diagnostic imaging / Q000473:pathology*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D062706:Prodromal Symptoms; D011618:Psychotic Disorders / Q000473:pathology*; D055815:Young Adult
keywords: CHR; MRI; Prodromal; Psychosis; Schizophrenia; Ventricle