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

• 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
• Journal Title: MOLECULAR PSYCHIATRY
• Volume: Volume 28, Number 3
• Publisher: SPRINGERNATURE | 2022-11-25, Pages 1182-1189
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1038/s41380-022-01870-7
• Subjects: Health Sciences, Radiology; Health Sciences, Mental Health
• Keywords: Science & Technology; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; Neurosciences; Psychiatry; Neurosciences & Neurology; HUMAN CEREBRAL-CORTEX; NEUROANATOMICAL ABNORMALITIES; SYNAPTIC PLASTICITY; PREFRONTAL CORTEX; SOCIAL ADVERSITY; SCHIZOPHRENIA; ONSET; INDIVIDUALS; MRI; DYSCONNECTION

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.