Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis
Authors: Baldwin Helen , Radua Joaquim , Antoniades Mathilde , Haas Shalaila S. , Frangou Sophia , Agartz Ingrid , Allen Paul , Andreassen Ole A. , Atkinson Kimberley , Bachman Peter , Baeza Inmaculada , Bartholomeusz Cali F. , Chee Michael W. L. , Colibazzi Tiziano , Cooper Rebecca E. , Corcoran Cheryl M. , Cropley Vanessa L. , Ebdrup Bjørn H. , Fortea Adriana , Glenthøj Louise Birkedal , Hamilton Holly K. , Haut Kristen M. , Hayes Rebecca A. , He Ying , Heekeren Karsten , Kaess Michael , Kasai Kiyoto , Katagiri Naoyuki , Kim Minah , Kindler Jochen , Klaunig Mallory J. , Koike Shinsuke , Koppel Alex , Kristensen Tina D. , Bin Kwak Yoo , Kwon Jun Soo , Lawrie Stephen M. , Lebedeva Irina , Lee Jimmy , Lin Ashleigh , Loewy Rachel L. , Mathalon Daniel H. , Michel Chantal , Mizrahi Romina , Møller Paul , Nelson Barnaby , Nemoto Takahiro , Nordholm Dorte , Omelchenko Maria A. , Pantelis Christos , Raghava Jayachandra M. , Røssberg Jan I. , Rössler Wulf , Salisbury Dean F. , Sasabayashi Daiki , Schall Ulrich , Smigielski Lukasz , Sugranyes Gisela , Suzuki Michio , Takahashi Tsutomu , Tamnes Christian K. , Tang Jinsong , Theodoridou Anastasia , Thomopoulos Sophia I. , Tomyshev Alexander S. , Uhlhaas Peter J. , Værnes Tor G. , van Amelsvoort Therese A. M. J. , Van Erp Theo G. M. , Waltz James A. , Westlye Lars T. , Wood Stephen J. , Zhou Juan H. , McGuire Philip , Thompson Paul M. , Jalbrzikowski Maria , Hernaus Dennis , Fusar-Poli Paolo ,   the ENIGMA Clinical High Risk for Psychosis Working Group, de la Fuente-Sandoval Camilo , Catalano Sabrina , Hubl Daniela , Schiffman Jason , Venegoni Enea D. , Hooker Christine I. , Rasser Paul E. , Hegelstad Wenche ten Velden , Resch Franz , Lemmers-Jansen Imke L. J. , Amminger G. Paul , Chen Xiaogang , Cho Kang Ik K. , Glenthøj Birte Yding , de Haan Lieuwe , Harris Matthew A. , Hwang Wu Jeong , León-Ortiz Pablo , Ma Xiaoqian , McGorry Patrick , Mora-Durán Ricardo , Mizuno Masafumi , Nordentoft Merete , Ouyang Lijun , Pariente Jose C. , Reyes-Madrigal Francisco , Sørensen Mikkel E. , Velakoulis Dennis , Vinogradov Sophia , Wenneberg Christina , Yamasue Hidenori , Yuan Liu , Yung Alison R. 
Published: July 2022

Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the ‘normativeness’ of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.