Accelerated cortical thinning precedes and predicts conversion to psychosis: The NAPLS3 longitudinal study of youth at clinical high-risk

• Type of Material: Article
• Authors: Meghan A Collins, Yale University; Jie Lisa Ji, Yale University; Yoonho Chung, McLean Hospital; Cole A Lympus, Yale University; Yvette Afriyie-Agyemang, University of Pittsburgh; Jean M Addington, University of Calgary; Bradley G Goodyear, University of Calgary; Carrie E Bearden, University of California Los Angeles; Kristin S Cadenhead, University of California San Diego; Heline Mirzakhanian, University of California San Diego; Ming T Tsuang, University of California San Diego; Barbara A Cornblatt, Zucker Hillside Hospital; Ricardo E Carrion, Zucker Hillside Hospital; Matcheri Keshavan, Harvard Medical School; William S Stone, Harvard Medical School; Daniel Mathalon, UCSF, and SFVA Medical Center, San Francisco; Diana O Perkins, University of North Carolina; Elaine Walker, Emory University; Scott W Woods, Yale University; Albert R Powers, Yale University; Alan Anticevic, Yale University; Tyrone D Cannon, Yale University
• Language: English
• Date: 2022-11-25
• Publisher: SPRINGERNATURE
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41380-022-01870-7
• Title of Journal or Parent Work: MOLECULAR PSYCHIATRY
• Volume: 28
• Issue: 3
• Start Page: 1182
• End Page: 1189
• Grant/Funding Information: This work was supported by the National Science Foundation (NSF) (No. DGE-1752134) to Ms. Collins, by the National Institute of Mental Health grant U01MH081984 to Dr. Addington; grant U01MH081928 to Dr. Stone; grant U01MH081944 to Dr. Cadenhead; grant U01MH081902 to Drs. Cannon and Bearden; grant U01MH082004 to Dr. Perkins; grant U01MH081988 to Dr. Walker; grant U01MH082022 to Dr. Woods; grant U01MH076989 to Dr. Mathalon; grant UO1MH081857 to Dr. Cornblatt; grants 1U01MH121766, 5R01MH112189, and 5R01MH108590 to Dr. Anticevic; grant T32MH125786 to Dr. Chung.
• Keywords: PREFRONTAL CORTEX; SYNAPTIC PLASTICITY; INDIVIDUALS; Science & Technology; MRI; DYSCONNECTION; NEUROANATOMICAL ABNORMALITIES; Biochemistry & Molecular Biology; SCHIZOPHRENIA; Life Sciences & Biomedicine; ONSET; Neurosciences & Neurology; SOCIAL ADVERSITY; Neurosciences; HUMAN CEREBRAL-CORTEX; Psychiatry
• Research Categories: Health Sciences, Mental Health; Health Sciences, Radiology

Abstract

Progressive grey matter loss has been demonstrated among clinical high-risk (CHR) individuals who convert to psychosis, but it is unknown whether these changes occur prior to psychosis onset. Identifying illness-related neurobiological mechanisms that occur prior to conversion is essential for targeted early intervention. Among participants in the third wave of the North American Prodrome Longitudinal Study (NAPLS3), this report investigated if steeper cortical thinning was observable prior to psychosis onset among CHR individuals who ultimately converted (CHR-C) and assessed the shortest possible time interval in which rates of cortical thinning differ between CHR-C, CHR non-converters (CHR-NC), and health controls (HC). 338 CHR-NC, 42 CHR-C, and 62 HC participants (age 19.3±4.2, 44.8% female, 52.5% racial/ethnic minority) completed up to 5 MRI scans across 8 months. Accelerated thinning among CHR-C compared to CHR-NC and HC was observed in multiple prefrontal, temporal, and parietal cortical regions. CHR-NC also exhibited accelerated cortical thinning compared to HC in several of these areas. Greater percent decrease in cortical thickness was observed among CHR-C compared to other groups across 2.9±1.8 months, on average, in several cortical areas. ROC analyses discriminating CHR-C from CHR-NC by percent thickness change in a left hemisphere region of interest, scanner, age, age2, and sex had an AUC of 0.74, with model predictive power driven primarily by percent thickness change. Findings indicate that accelerated cortical thinning precedes psychosis onset and differentiates CHR-C from CHR-NC and HC across short time intervals. Mechanisms underlying cortical thinning may provide novel treatment targets prior to psychosis onset.