. 2022 Jul 26;12(1):297.

doi: 10.1038/s41398-022-02057-y.

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

Helen Baldwin^{1

2}, Joaquim Radua^{3

4

5}, Mathilde Antoniades⁶, Shalaila S Haas⁶, Sophia Frangou^{6

7}, Ingrid Agartz^{8

9

10

11}, Paul Allen^{12

13}, Ole A Andreassen^{11

14}, Kimberley Atkinson¹⁵, Peter Bachman¹⁶, Inmaculada Baeza¹⁷, Cali F Bartholomeusz^{18

19}, Michael W L Chee²⁰, Tiziano Colibazzi^{21

22}, Rebecca E Cooper²³, Cheryl M Corcoran^{6

24}, Vanessa L Cropley^{23

25}, Bjørn H Ebdrup^{26

27}, Adriana Fortea²⁸, Louise Birkedal Glenthøj²⁹, Holly K Hamilton^{30

31}, Kristen M Haut³², Rebecca A Hayes¹⁶, Ying He³³, Karsten Heekeren^{34

35}, Michael Kaess^{36

37}, Kiyoto Kasai^{38

39

40}, Naoyuki Katagiri⁴¹, Minah Kim^{42

43}, Jochen Kindler³⁷, Mallory J Klaunig⁴⁴, Shinsuke Koike^{39

45}, Alex Koppel⁴⁶, Tina D Kristensen^{26

29}, Yoo Bin Kwak^{47

48}, Jun Soo Kwon^{42

43}, Stephen M Lawrie¹⁵, Irina Lebedeva⁴⁹, Jimmy Lee^{48

50}, Ashleigh Lin⁵¹, Rachel L Loewy³⁰, Daniel H Mathalon^{30

31}, Chantal Michel³⁷, Romina Mizrahi^{52

53}, Paul Møller⁵⁴, Barnaby Nelson^{18

19}, Takahiro Nemoto⁴¹, Dorte Nordholm²⁹, Maria A Omelchenko⁵⁵, Christos Pantelis^{23

56}, Jayachandra M Raghava^{26

57

58}, Jan I Røssberg¹⁴, Wulf Rössler^{35

59}, Dean F Salisbury¹⁶, Daiki Sasabayashi^{60

61}, Ulrich Schall^{62

63}, Lukasz Smigielski^{35

64}, Gisela Sugranyes¹⁷, Michio Suzuki^{60

61}, Tsutomu Takahashi^{60

61}, Christian K Tamnes^{8

14

65}, Jinsong Tang^{66

67}, Anastasia Theodoridou³⁵, Sophia I Thomopoulos⁶⁸, Alexander S Tomyshev⁴⁹, Peter J Uhlhaas^{69

70}, Tor G Værnes^{14

71}, Therese A M J van Amelsvoort⁷², Theo G M Van Erp^{73

74}, James A Waltz⁷⁵, Lars T Westlye^{11

14

76}, Stephen J Wood^{18

19

77}, Juan H Zhou^{20

78}, Philip McGuire¹³, Paul M Thompson⁶⁸, Maria Jalbrzikowski^{16

79

80}, Dennis Hernaus⁷², Paolo Fusar-Poli^{3

81

82

83}; ENIGMA Clinical High Risk for Psychosis Working Group

Collaborators, Affiliations

Collaborators

Affiliations

¹ Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. helen.baldwin@kcl.ac.uk.
² National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK. helen.baldwin@kcl.ac.uk.
³ Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁴ Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBERSAM, Barcelona, Spain.
⁵ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁶ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
⁷ Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
⁸ Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
⁹ Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
¹⁰ Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹¹ KG Jebsen Center for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
¹² Department of Psychology, University of Roehampton, London, UK.
¹³ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹⁴ NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹⁵ Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
¹⁶ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁷ Department of Child and Adolescent Psychiatry and Psychology, Institute of Neuroscience, 2017SGR-881, Hospital Clinic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Universitat de Barcelona, Barcelona, Spain.
¹⁸ Centre for Youth Mental Health, University of Melbourne, Melbourne, VIC, Australia.
¹⁹ Orygen, Melbourne, VIC, Australia.
²⁰ Center for Sleep and Cognition, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
²¹ Department of Psychiatry, Columbia University, New York City, NY, USA.
²² New York State Psychiatric Institute, New York City, NY, USA.
²³ Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne & Melbourne Health, Carlton South, VIC, Australia.
²⁴ Mental Illness Research, Education, and Clinical Center, James J Peters VA Medical Center, New York City, NY, USA.
²⁵ Centre for Mental Health, Faculty of Health, Arts and Design, School of Health Sciences, Swinburne University, Melbourne, VIC, Australia.
²⁶ Centre for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Centre Glostrup, Copenhagen University Hospital, Glostrup, Denmark.
²⁷ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
²⁸ Department of Child and Adolescent Psychiatry and Psychology, Institute of Neuroscience, Hospital Clinic Barcelona, Fundació Clínic Recerca Biomèdica, Universitat de Barcelona, Barcelona, Spain.
²⁹ Copenhagen Research Center for Mental Health, Mental Health Center Copenhagen, University of Copenhagen, Copenhagen, Denmark.
³⁰ Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, USA.
³¹ San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA.
³² Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA.
³³ National Clinical Research Center for Mental Disorders and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
³⁴ Department of Psychiatry and Psychotherapy I, LVR-Hospital Cologne, Cologne, Germany.
³⁵ Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland.
³⁶ Department of Child and Adolescent Psychiatry, Center of Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany.
³⁷ University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.
³⁸ Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
³⁹ The University of Tokyo Institute for Diversity and Adaptation of Human Mind, Tokyo, Japan.
⁴⁰ The International Research Center for Neurointelligence at The University of Tokyo Institutes for Advanced Study, The University of Tokyo, Tokyo, Japan.
⁴¹ Department of Neuropsychiatry, Toho University School of Medicine, Tokyo, Japan.
⁴² Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
⁴³ Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁴⁴ Department of Psychology, University of Maryland, Baltimore County, MD, USA.
⁴⁵ Center for Evolutionary Cognitive Sciences, Graduate School of Art and Sciences, The University of Tokyo, Tokyo, Japan.
⁴⁶ Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
⁴⁷ Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea.
⁴⁸ Department of Psychosis, Institute of Mental Health, Singapore, Singapore.
⁴⁹ Laboratory of Neuroimaging and Multimodal Analysis, Mental Health Research Center, Moscow, Russian Federation.
⁵⁰ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
⁵¹ Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia.
⁵² Douglas Research Center, Montreal, QC, Canada.
⁵³ Department of Psychiatry, McGill University, Montreal, QC, Canada.
⁵⁴ Department for Mental Health Research and Development, Division of Mental Health and Addiction, Vestre Viken Hospital Trust, Drammen, Norway.
⁵⁵ Department of Youth Psychiatry, Mental Health Research Center, Moscow, Russian Federation.
⁵⁶ Florey Institute of Neuroscience and Mental Health, Center for Mental Health, Parkville, VIC, Australia.
⁵⁷ Department of Clinical Physiology, Nuclear Medicine and PET, Functional Imaging Unit, University of Copenhagen, Glostrup, Denmark.
⁵⁸ Centre for Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
⁵⁹ Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁶⁰ Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.
⁶¹ Research Center for Idling Brain Science, University of Toyama, Toyama, Japan.
⁶² Priority Centre for Brain and Mental Health Research, The University of Newcastle, Newcastle, NSW, Australia.
⁶³ Priority Research Centre Grow Up Well, The University of Newcastle, Newcastle, NSW, Australia.
⁶⁴ Department of Child and Adolescent Psychiatry, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁶⁵ PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway.
⁶⁶ Department of Psychiatry, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
⁶⁷ Key Laboratory of Medical Neurobiology of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China.
⁶⁸ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁶⁹ Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK.
⁷⁰ Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany.
⁷¹ Early Intervention in Psychosis Advisory Unit for South-East Norway, TIPS Sør-Øst, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁷² Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Faculty of Health Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
⁷³ Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, CA, USA.
⁷⁴ Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA.
⁷⁵ Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
⁷⁶ Department of Psychology, University of Oslo, Oslo, Norway.
⁷⁷ School of Psychology, University of Birmingham, Birmingham, UK.
⁷⁸ Center for Translational Magnetic Resonance Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁷⁹ Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, MA, USA.
⁸⁰ Department of Psychiatry, Harvard Medical School, Cambridge, MA, USA.
⁸¹ National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK.
⁸² OASIS Service, South London and Maudsley NHS Foundation Trust, London, UK.
⁸³ Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.

PMID: 35882855
PMCID: PMC9325730
DOI: 10.1038/s41398-022-02057-y

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

Helen Baldwin et al. Transl Psychiatry. 2022.

. 2022 Jul 26;12(1):297.

doi: 10.1038/s41398-022-02057-y.

Authors

Collaborators

Affiliations

¹ Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. helen.baldwin@kcl.ac.uk.
² National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK. helen.baldwin@kcl.ac.uk.
³ Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁴ Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBERSAM, Barcelona, Spain.
⁵ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁶ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
⁷ Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
⁸ Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
⁹ Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
¹⁰ Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹¹ KG Jebsen Center for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
¹² Department of Psychology, University of Roehampton, London, UK.
¹³ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹⁴ NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹⁵ Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
¹⁶ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁷ Department of Child and Adolescent Psychiatry and Psychology, Institute of Neuroscience, 2017SGR-881, Hospital Clinic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Universitat de Barcelona, Barcelona, Spain.
¹⁸ Centre for Youth Mental Health, University of Melbourne, Melbourne, VIC, Australia.
¹⁹ Orygen, Melbourne, VIC, Australia.
²⁰ Center for Sleep and Cognition, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
²¹ Department of Psychiatry, Columbia University, New York City, NY, USA.
²² New York State Psychiatric Institute, New York City, NY, USA.
²³ Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne & Melbourne Health, Carlton South, VIC, Australia.
²⁴ Mental Illness Research, Education, and Clinical Center, James J Peters VA Medical Center, New York City, NY, USA.
²⁵ Centre for Mental Health, Faculty of Health, Arts and Design, School of Health Sciences, Swinburne University, Melbourne, VIC, Australia.
²⁶ Centre for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Centre Glostrup, Copenhagen University Hospital, Glostrup, Denmark.
²⁷ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
²⁸ Department of Child and Adolescent Psychiatry and Psychology, Institute of Neuroscience, Hospital Clinic Barcelona, Fundació Clínic Recerca Biomèdica, Universitat de Barcelona, Barcelona, Spain.
²⁹ Copenhagen Research Center for Mental Health, Mental Health Center Copenhagen, University of Copenhagen, Copenhagen, Denmark.
³⁰ Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, USA.
³¹ San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA.
³² Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA.
³³ National Clinical Research Center for Mental Disorders and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
³⁴ Department of Psychiatry and Psychotherapy I, LVR-Hospital Cologne, Cologne, Germany.
³⁵ Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland.
³⁶ Department of Child and Adolescent Psychiatry, Center of Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany.
³⁷ University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.
³⁸ Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
³⁹ The University of Tokyo Institute for Diversity and Adaptation of Human Mind, Tokyo, Japan.
⁴⁰ The International Research Center for Neurointelligence at The University of Tokyo Institutes for Advanced Study, The University of Tokyo, Tokyo, Japan.
⁴¹ Department of Neuropsychiatry, Toho University School of Medicine, Tokyo, Japan.
⁴² Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
⁴³ Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁴⁴ Department of Psychology, University of Maryland, Baltimore County, MD, USA.
⁴⁵ Center for Evolutionary Cognitive Sciences, Graduate School of Art and Sciences, The University of Tokyo, Tokyo, Japan.
⁴⁶ Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
⁴⁷ Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea.
⁴⁸ Department of Psychosis, Institute of Mental Health, Singapore, Singapore.
⁴⁹ Laboratory of Neuroimaging and Multimodal Analysis, Mental Health Research Center, Moscow, Russian Federation.
⁵⁰ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
⁵¹ Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia.
⁵² Douglas Research Center, Montreal, QC, Canada.
⁵³ Department of Psychiatry, McGill University, Montreal, QC, Canada.
⁵⁴ Department for Mental Health Research and Development, Division of Mental Health and Addiction, Vestre Viken Hospital Trust, Drammen, Norway.
⁵⁵ Department of Youth Psychiatry, Mental Health Research Center, Moscow, Russian Federation.
⁵⁶ Florey Institute of Neuroscience and Mental Health, Center for Mental Health, Parkville, VIC, Australia.
⁵⁷ Department of Clinical Physiology, Nuclear Medicine and PET, Functional Imaging Unit, University of Copenhagen, Glostrup, Denmark.
⁵⁸ Centre for Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
⁵⁹ Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁶⁰ Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.
⁶¹ Research Center for Idling Brain Science, University of Toyama, Toyama, Japan.
⁶² Priority Centre for Brain and Mental Health Research, The University of Newcastle, Newcastle, NSW, Australia.
⁶³ Priority Research Centre Grow Up Well, The University of Newcastle, Newcastle, NSW, Australia.
⁶⁴ Department of Child and Adolescent Psychiatry, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁶⁵ PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway.
⁶⁶ Department of Psychiatry, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
⁶⁷ Key Laboratory of Medical Neurobiology of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China.
⁶⁸ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁶⁹ Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK.
⁷⁰ Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany.
⁷¹ Early Intervention in Psychosis Advisory Unit for South-East Norway, TIPS Sør-Øst, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁷² Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Faculty of Health Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
⁷³ Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, CA, USA.
⁷⁴ Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA.
⁷⁵ Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
⁷⁶ Department of Psychology, University of Oslo, Oslo, Norway.
⁷⁷ School of Psychology, University of Birmingham, Birmingham, UK.
⁷⁸ Center for Translational Magnetic Resonance Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁷⁹ Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, MA, USA.
⁸⁰ Department of Psychiatry, Harvard Medical School, Cambridge, MA, USA.
⁸¹ National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK.
⁸² OASIS Service, South London and Maudsley NHS Foundation Trust, London, UK.
⁸³ Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.

PMID: 35882855
PMCID: PMC9325730
DOI: 10.1038/s41398-022-02057-y

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

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.

Figures

**Fig. 1. Forest plot of the variability ratio (VR) of cortical surface area (SA) measures in CHR-P compared with healthy controls.**
CHR-P clinical high risk for psychosis, STS superior temporal sulcus, VR variability ratio.

**Fig. 2. Forest plot of the variability ratio (VR) of cortical thickness (CT) measures in CHR-P compared with healthy controls.**
CHR-P clinical high risk for psychosis, STS superior temporal sulcus, VR variability ratio.

**Fig. 3. Forest plot of the variability ratio (VR) of subcortical volume (SV) measures in CHR-P compared with healthy controls.**
CHR-P clinical high risk for psychosis, VR variability ratio.

Fig. 4. Violin plots comparing the distribution of PBSI scores between individuals at CHR-P and healthy controls, across surface area (PBSI_SA), cortical thickness (PBSI_CT), and subcortical volume (PBSI_SV); the mid-point indicates the group mean.
PBSI Person-Based Similarity Index, SA surface area, CT cortical thickness, SV subcortical volume. All three phenotypes demonstrate significantly lower similarity in PBSI profiles in the CHR-P group compared with healthy controls, across PBSI_SA (p < 0.01), PBSI_CT (p < 0.01), PBSI_SV (p < 0.01).

**Fig. 5. A bar chart representing the percentage of the CHR-P sample who demonstrate marked deviation from the ‘normative’ neuroanatomical profile.**
CHR-P clinical high risk for psychosis, PBSI_SA_Z person-based similarity index surface area z-scores, PBSI_CT_Z person-based similarity index cortical thickness z-scores, PBSI_SV_Z person-based similarity index subcortical volume z-scores.

See this image and copyright information in PMC

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

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

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Conflict of interest statement

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