biostudies-literatureLiu SMinistry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)National Research Foundation of Korea (NRF)Lundbeckfonden (Lundbeck Foundation)Norges Forskningsråd (Research Council of Norway)MOH | National Medical Research Council (NMRC)Korea Basic Science Institute (KBSI)Medical Research CouncilDepartment of Health | National Health and Medical Research Council (NHMRC)Russian Foundation for Basic Research (RFBR)Japan Agency for Medical Research and Development (AMED)National Natural Science Foundation of China (National Science Foundation of China)1707-1722https://www.ebi.ac.uk/biostudies/studies/S-EPMC12916477biostudies-literatureUnknown31(3)Brain network architecture is anticipated to influence future grey matter loss in individuals at Clinical High Risk (CHR) for psychosis. However, existing studies on grey matter structural network properties in CHR are scarce and constrained by small sample sizes. Here, we examined network topology differences comparing a) CHR versus healthy controls (HC); b) CHR who transitioned to psychosis (CHR-T) versus those who did not (CHR-NT); and c) different subsyndromes. We included structural scans from 1842 CHR individuals and 1417 HC individuals from 31 sites within the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium. At the global level, CHR individuals exhibited lower structural covariance (q < 0.001; Cohen's d = 0.164) and less optimal structural network configuraMolecular psychiatryStructural covariance network topology in individuals at clinical high risk for psychosis: the ENIGMA-CHR Study.PMC12916477INT19/000215T32MH15144 and K23 MH85063JP18dm0307001, JP18dm0307004, and JP19dm020706921-BR-03-011196508 and 1150083223272223273PI11/02684 and PI15/00509R01MH1052461177370 and 10657422020M3E5D9079910MR/L011689/1566529 and 3592231027532, 1137687 and 10277412019R1C1C1002457MH076989T32MH122394K23MH086618 and R01MH081051R25-A2701 and R287-2018-1485G0700995K01MH112774 and R01MH1296365R01MH11503181871057NMRC/TCR/003/200820-013-00748Ebdrup BHSorensen MEKaess MMathalon DHPariente JCJalbrzikowski MRasser PEHegelstad WTVSchiffman JWenneberg CBachman PKoike SWaltz JALeon-Ortiz PYuan LWestlye LTLin AHe YMora-Duran RBaldwin HPantelis CDolz MVelakoulis DHamilton HKRaghava JMCropley VLHaas SSLee JSasabayashi DKim MKristensen TDLemmers-Jansen ILResch FTang JVærnes TGHooker CIYamasue Hvan Amelsvoort TAVinogradov SAmminger GPTor JHernaus DAgartz INordholm DCooper REWood SJRossberg JIAllen PTomyshev ASKlaunig MJReyes-Madrigal FVia ESchmidt ALawrie SMOuyang Lde Haan Lde la Fuente-Sandoval CHeekeren KNordentoft MZhou JHSchall UAndreassen OAColibazzi TCatalano SNelson BChen XLoewy RLSalisbury DFRivera-Chavez LFMoller PFortea ATheodoridou AMichel CTamnes CKHayes RAChee MWThompson PMKwak YBMcGorry PSuzuki MMa XLiu SKwon JSChoi SFusar-Poli PTakahashi TYung ARKindler JENIGMA Clinical High Risk for Psychosis Working GroupHwang WJGlenthoj BYMizrahi RMizuno MKatagiri NMunoz-Samons DUhlhaas PJBaeza IHubl DMcGuire PHaut KMOmelchenko MASmigielski LBorgwardt SRossler WKasai KNemoto TBartholomeusz CFLebedeva ICho KIKThomopoulos SIHorton LECorcoran CMGlenthoj LBSugranyes GfalseStructural covariance network topology in individuals at clinical high risk for psychosis: the ENIGMA-CHR Study.Brain network architecture is anticipated to influence future grey matter loss in individuals at Clinical High Risk (CHR) for psychosis. However, existing studies on grey matter structural network properties in CHR are scarce and constrained by small sample sizes. Here, we examined network topology differences comparing a) CHR versus healthy controls (HC); b) CHR who transitioned to psychosis (CHR-T) versus those who did not (CHR-NT); and c) different subsyndromes. We included structural scans from 1842 CHR individuals and 1417 HC individuals from 31 sites within the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium. At the global level, CHR individuals exhibited lower structural covariance (q < 0.001; Cohen's d = 0.164) and less optimal structural network configura2026-01-01T00:00:00Z2026 Mar2026-07-16T09:57:49.547Z2026-07-09T10:49:40.931ZS-EPMC129164774112574310.1038/s41380-025-03304-6