Ventricular enlargement and progressive reduction of cortical gray matter are linked in prodromal youth who develop psychosis

• Type of Material: Article
• Authors: Yoonho Chung, Yale University; Kristen M. Haut, Rush University; George He, Yale University; Theo G.M. van Erp, University of California Irvine; Sarah McEwen, University of California Los Angeles; Jean Addington, University of Calgary; Carrie E. Bearden, University of California Los Angeles; Kristin Cadenhead, University of California San Diego; Barbara Cornblatt, Zucker Hillside Hospital; Daniel H. Mathalon, University of California San Francisco; Thomas McGlashan, Yale University; Diana Perkins, University of North Carolina; Larry J. Seidman, Harvard Medical School; Ming Tsuang, University of California San Diego; Elaine Walker, Emory University; Scott W. Woods, Yale University; Tyrone D. Cannon, Yale University
• Language: English
• Date: 2017-11
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Elsevier B.V. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.schres.2017.02.014
• Title of Journal or Parent Work: Schizophrenia Research
• ISSN: 0920-9964
• Volume: 189
• Start Page: 169
• End Page: 174
• Grant/Funding Information: This work was supported by a collaborative U01 award from the National Institute of Mental Health at the National Institutes of Health (MH081902 to TDC; MH081857 to BAC; MH081988 to EW; MH081928 to LJS; MH082004 to DP; MH082022 to KC; MH081984 to JA; MH082022 to SWW) and NIMH P50 MH066286 and Staglin Music Festival for Mental Health (CEB), NIMH P50 MH080272, and the Commonwealth of Massachusetts (SCDMH82101008006) to L.J.S.
• Keywords: CHR; Ventricle; psychosis; Schizophrenia; MRI; prodromal
• Research Categories: Psychology, Behavioral; Psychology, Clinical

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.