Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis

the ENIGMA Clinical High Risk for Psychosis Working Group

doi:10.1038/s41398-022-02057-y

Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis

the ENIGMA Clinical High Risk for Psychosis Working Group

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

© 2022, The Author(s).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.

Original language	English
Article number	297
Journal	Translational Psychiatry
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41398-022-02057-y
Publication status	Published - 1 Dec 2022

Funding

HB is funded by a National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre doctoral studentship. SF is supported by the National Institute of Mental Health under grant R01MH113619. CMC is supported by R01MH107558 and R01MH115332. BN is supported by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship (1137687). AL is supported by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship (#1148793). CKT is supported by the Research Council of Norway (223273, 288083, 323951) and the South-Eastern Norway Regional Health Authority (2019069, 2021070, 500189). PMT is supported by NIH grants R01MH116147, P41EB015922, and R01AG058854. VC is supported by a National Health and Medical Research Council (NHMRC) Investigator Grant (1177370). LTW is supported by the European Research Council under the European Union’s Horizon 2020 research and Innovation program (ERC StG, Grant 802998). GS is supported by the Fundació Clínic Recerca Biomèdica, the Brain and Behavior Research Foundation (NARSAD Young Investigator Award 2017, grant ID: 26731), the Alicia Koplowitz Foundation and the Spanish Ministry of Health, Instituto de Salud Carlos III “Health Research Fund” (PI15/0444; PI18/0242; PI18/00976). CF-S was supported by grants 182279 and 261895 from the Consejo Nacional de Ciencia y Tecnología, grants from CONACYT’s Sistema Nacional de Investigadores, and grant R21 MH117434 from the National Institutes of Health. CP was supported by a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship (1105825), an NHMRC L3 Investigator Grant (1196508), and NHMRC Program Grant (ID: 1150083). Core funding for ENIGMA was provided by the NIH Big Data to Knowledge (BD2K) program under consortium grant U54 EB020403 to PMT. PMT receives partial research support from Biogen, Inc., for research unrelated to this manuscript. OAA is a consultant to HealthLytix. CP has received honoraria for talks at educational meetings and has served on an advisory board for Lundbeck, Australia Pty Ltd. BHE has received lecture fees Otsuka Pharma Scandinavia AB, Boehringer Ingelheim, and Lundbeck Pharma A/S.

Funders	Funder number
Biogen, Inc.
Fundació Clínic Recerca Biomèdica
National Institutes of Health	1150083, 1177370, R01AG058854, 1105825, 1196508, U54 EB020403
National Institute of Mental Health	R01MH107558, R01MH115332, R01MH116147, R01MH113619
National Institute of Biomedical Imaging and Bioengineering	P41EB015922
Brain and Behavior Research Foundation
Fundación Alicia Koplowitz
National Alliance for Research on Schizophrenia and Depression	26731
Horizon 2020 Framework Programme
NIHR Maudsley Biomedical Research Centre
National Institute for Health and Care Research
European Research Council	802998
National Health and Medical Research Council	1137687, 1148793
Consejo Nacional de Ciencia y Tecnología
Instituto de Salud Carlos III	PI15/0444, 182279, 261895, PI18/00976, PI18/0242
Norges forskningsråd	223273, 288083, 323951
Helse Sør-Øst RHF	2019069, 500189, 2021070
Consejería de Salud y Familias, Junta de Andalucía
Sistema Nacional de Investigadores	R21 MH117434

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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@article{353b49fda1a24e9a84063fd45c2dcb8d,

title = "Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis",

abstract = "{\textcopyright} 2022, The Author(s).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 {\textquoteleft}normativeness{\textquoteright} 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.",

author = "H. Baldwin and J. Radua and M. Antoniades and S.S. Haas and S. Frangou and I. Agartz and P. Allen and O.A. Andreassen and K. Atkinson and P. Bachman and I. Baeza and C.F. Bartholomeusz and M.W.L. Chee and T. Colibazzi and R.E. Cooper and C.M. Corcoran and V.L. Cropley and B.H. Ebdrup and A. Fortea and L.B. Glenth{\o}j and H.K. Hamilton and K.M. Haut and R.A. Hayes and Y. He and K. Heekeren and M. Kaess and K. Kasai and N. Katagiri and M. Kim and J. Kindler and M.J. Klaunig and S. Koike and A. Koppel and T.D. Kristensen and {Bin Kwak}, Y. and J.S. Kwon and S.M. Lawrie and I. Lebedeva and J. Lee and A. Lin and R.L. Loewy and D.H. Mathalon and C. Michel and R. Mizrahi and P. M{\o}ller and B. Nelson and T. Nemoto and D. Nordholm and M.A. Omelchenko and C. Pantelis and J.M. Raghava and J.I. R{\o}ssberg and W. R{\"o}ssler and D.F. Salisbury and D. Sasabayashi and U. Schall and L. Smigielski and G. Sugranyes and M. Suzuki and T. Takahashi and C.K. Tamnes and J. Tang and A. Theodoridou and S.I. Thomopoulos and A.S. Tomyshev and P.J. Uhlhaas and T.G. V{\ae}rnes and {van Amelsvoort}, T.A.M.J. and {Van Erp}, T.G.M. and J.A. Waltz and L.T. Westlye and S.J. Wood and J.H. Zhou and P. McGuire and P.M. Thompson and M. Jalbrzikowski and D. Hernaus and P. Fusar-Poli and {de la Fuente-Sandoval}, C. and S. Catalano and D. Hubl and J. Schiffman and E.D. Venegoni and C.I. Hooker and P.E. Rasser and W.V. Hegelstad and F. Resch and I.L.J. Lemmers-Jansen and G.P. Amminger and X. Chen and K.I.K. Cho and B.Y. Glenth{\o}j and {de Haan}, L. and M.A. Harris and W.J. Hwang and P. Le{\'o}n-Ortiz and X. Ma and P. McGorry and R. Mora-Dur{\'a}n and M. Mizuno and M. Nordentoft and L. Ouyang and J.C. Pariente and F. Reyes-Madrigal and M.E. S{\o}rensen and D. Velakoulis and S. Vinogradov and C. Wenneberg and H. Yamasue and L. Yuan and A.R. Yung and {the ENIGMA Clinical High Risk for Psychosis Working Group}",

year = "2022",

month = dec,

day = "1",

doi = "10.1038/s41398-022-02057-y",

language = "English",

volume = "12",

journal = "Translational Psychiatry",

issn = "2158-3188",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis

AU - Baldwin, H.

AU - Radua, J.

AU - Antoniades, M.

AU - Haas, S.S.

AU - Frangou, S.

AU - Agartz, I.

AU - Allen, P.

AU - Andreassen, O.A.

AU - Atkinson, K.

AU - Bachman, P.

AU - Baeza, I.

AU - Bartholomeusz, C.F.

AU - Chee, M.W.L.

AU - Colibazzi, T.

AU - Cooper, R.E.

AU - Corcoran, C.M.

AU - Cropley, V.L.

AU - Ebdrup, B.H.

AU - Fortea, A.

AU - Glenthøj, L.B.

AU - Hamilton, H.K.

AU - Haut, K.M.

AU - Hayes, R.A.

AU - He, Y.

AU - Heekeren, K.

AU - Kaess, M.

AU - Kasai, K.

AU - Katagiri, N.

AU - Kim, M.

AU - Kindler, J.

AU - Klaunig, M.J.

AU - Koike, S.

AU - Koppel, A.

AU - Kristensen, T.D.

AU - Bin Kwak, Y.

AU - Kwon, J.S.

AU - Lawrie, S.M.

AU - Lebedeva, I.

AU - Lee, J.

AU - Lin, A.

AU - Loewy, R.L.

AU - Mathalon, D.H.

AU - Michel, C.

AU - Mizrahi, R.

AU - Møller, P.

AU - Nelson, B.

AU - Nemoto, T.

AU - Nordholm, D.

AU - Omelchenko, M.A.

AU - Pantelis, C.

AU - Raghava, J.M.

AU - Røssberg, J.I.

AU - Rössler, W.

AU - Salisbury, D.F.

AU - Sasabayashi, D.

AU - Schall, U.

AU - Smigielski, L.

AU - Sugranyes, G.

AU - Suzuki, M.

AU - Takahashi, T.

AU - Tamnes, C.K.

AU - Tang, J.

AU - Theodoridou, A.

AU - Thomopoulos, S.I.

AU - Tomyshev, A.S.

AU - Uhlhaas, P.J.

AU - Værnes, T.G.

AU - van Amelsvoort, T.A.M.J.

AU - Van Erp, T.G.M.

AU - Waltz, J.A.

AU - Westlye, L.T.

AU - Wood, S.J.

AU - Zhou, J.H.

AU - McGuire, P.

AU - Thompson, P.M.

AU - Jalbrzikowski, M.

AU - Hernaus, D.

AU - Fusar-Poli, P.

AU - de la Fuente-Sandoval, C.

AU - Catalano, S.

AU - Hubl, D.

AU - Schiffman, J.

AU - Venegoni, E.D.

AU - Hooker, C.I.

AU - Rasser, P.E.

AU - Hegelstad, W.V.

AU - Resch, F.

AU - Lemmers-Jansen, I.L.J.

AU - Amminger, G.P.

AU - Chen, X.

AU - Cho, K.I.K.

AU - Glenthøj, B.Y.

AU - de Haan, L.

AU - Harris, M.A.

AU - Hwang, W.J.

AU - León-Ortiz, P.

AU - Ma, X.

AU - McGorry, P.

AU - Mora-Durán, R.

AU - Mizuno, M.

AU - Nordentoft, M.

AU - Ouyang, L.

AU - Pariente, J.C.

AU - Reyes-Madrigal, F.

AU - Sørensen, M.E.

AU - Velakoulis, D.

AU - Vinogradov, S.

AU - Wenneberg, C.

AU - Yamasue, H.

AU - Yuan, L.

AU - Yung, A.R.

AU - the ENIGMA Clinical High Risk for Psychosis Working Group

PY - 2022/12/1

Y1 - 2022/12/1

N2 - © 2022, The Author(s).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.

AB - © 2022, The Author(s).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.

UR - http://www.scopus.com/inward/record.url?scp=85135084731&partnerID=8YFLogxK

U2 - 10.1038/s41398-022-02057-y

DO - 10.1038/s41398-022-02057-y

M3 - Article

SN - 2158-3188

VL - 12

JO - Translational Psychiatry

JF - Translational Psychiatry

IS - 1

M1 - 297

ER -

Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis

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