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Thinner cortex is associated with psychosis onset in individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group mega-analysis

By ENIGMA Clinical High Risk for Psychosis Working Group, Maria Jalbrzikowski, Rebecca A. Hayes, Stephen J Wood, Dorte Nordholm, Juan Helen Zhou, Paolo Fusar-Poli, Peter J. Uhlhaas, Tsutomu Takahashi, Gisela Sugranyes, Yoo Bin Kwak, Daniel H. Mathalon, Naoyuki Katagiri, Christine I. Hooker, Lukasz Smigielski, Tiziano Colibazzi, Esther Via, Jinsong Tang, Shinsuke Koike, Paul E Rasser, Chantal Michel, Irina Lebedeva, Wenche ten Velden Hegelstad, Camilo de la Fuente-Sandoval, James A Waltz, Romina Mizrahi, Cheryl Corcoran, Franz Resch, Christian K Tamnes, Shalaila S. Haas, Imke L.J. Lemmers-Jansen, Ingrid Agartz, Paul Allen, Ole A Andreassen, Kimberley Atkinson, Peter Bachman, Inmaculada Baeza, Helen Baldwin, Cali F. Bartholomeusz, Stefan Borgwardt, Sabrina Catalano, Michael W.L. Chee, Xiaogang Chen, Kang Ik K. Cho, Rebecca E. Cooper, Vanessa L. Cropley, Montserrat Dolz, Bjorn H Ebdrup, Adriana Fortea, Louise Birkedal Glenthoj, Birte Yding Glenthoj, Lieuwe de Haan, Holly K. Hamilton, Mathew Harris, Kristen M. Haut, Ying He, Karsten Heekeren, Andreas Heinz, Daniela Hubl, Wu Jeong Hwang, Michael Kaess, Kiyoto Kasai, Minah Kim, Jochen Kindler, Mallory J. Klaunig, Alex Koppel, Tina Dam Kristensen, Jun Soo Kwon, Stephen M Lawrie, Jimmy Lee, Pablo Leon-Ortiz, Ashleigh Lin, Rachel L. Loewy, Xiaoqian Ma, Patrick McGorry, Philip McGuire, Masafumi Mizuno, Paul Moller, Tomas Moncada-Habib, Daniel Munoz-Samons, Barnaby Nelson, Takahiro Nemoto, Merete Nordentoft, Maria A. Omelchenko, Ketil Oppedal, Lijun Ouyang, Christos Pantelis, Jose C Pariente, Jayachandra Raghava, Francisco Reyes-Madrigal, Brian J. Roach, Jan Ivar Rossberg, Wulf Rossler, Dean F. Salisbury, Daiki Sasabayashi, Ulrich Schall, Jason Schiffman, Florian Schlagenhauf, Andre Schmidt, Mikkel Erlang Sorensen, Michio Suzuki, Anastasia Theodoridou, Alexander S Tomyshev, Jordina Tor, Tor G Vaernes, Dennis Velakoulis, Gloria D. Venegoni, Sophia Vinogradov, Christina Wenneberg, Lars T Westlye, Hidenori Yamasue, Liu Yuan, Alison R. Yung, Therese A.M.J. van Amelsvoort, Jessica Turner, Theo GM Van Erp, Paul M Thompson, Dennis Hernaus

Posted 06 Jan 2021
medRxiv DOI: 10.1101/2021.01.05.20248768

Abstract Importance: The ENIGMA clinical high risk for psychosis (CHR) initiative, the largest pooled CHR-neuroimaging sample to date, aims to discover robust neurobiological markers of psychosis risk in a sample with known heterogeneous outcomes. Objective: We investigated baseline structural neuroimaging differences between CHR subjects and healthy controls (HC), and between CHR participants who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-). We assessed associations with age by group and conversion status, and similarities between the patterns of effect size maps for psychosis conversion and those found in other large-scale psychosis studies. Design, Setting, and Participants. Baseline T1-weighted MRI data were pooled from 31 international sites participating in the ENIGMA CHR Working Group. MRI scans were processed using harmonized protocols and analyzed within a mega- and meta-analysis framework from January-October 2020. Main Outcome(s) and Measure(s): Measures of regional cortical thickness (CT), surface area (SA), and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR, HC) and conversion status (CHR-PS+, CHR-PS-, HC). Results: The final dataset consisted of 3,169 participants (CHR=1,792, HC=1,377, age range: 9.5 to 39.8 years, 45% female). Using longitudinal clinical information, we identified CHR-PS+ (N=253) and CHR-PS- (N=1,234). CHR exhibited widespread thinner cortex compared to HC (average d=-0.125, range: -0.09 to -0.17), but not SA or subcortical volume. Thinner cortex in the fusiform, superior temporal, and paracentral regions was associated with psychosis conversion (average d=-0.22). Age showed a stronger negative association with left fusiform and left paracentral CT in HC, compared to CHR-PS+. Regional CT psychosis conversion effect sizes resembled patterns of CT alterations observed in other ENIGMA studies of psychosis. Conclusions and Relevance: We provide evidence for widespread subtle CT reductions in CHR. The pattern of regions displaying greater CT alterations in CHR-PS+ were similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread CT disruptions coupled with abnormal age associations in CHR may point to disruptions in postnatal brain developmental processes.

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