This is a preprint.

It has not yet been peer reviewed by a journal.

The National Library of Medicine is running a pilot to include preprints that result from research funded by NIH in PMC and PubMed.

[Preprint]. 2023 Jan 18:2023.01.17.523348.

doi: 10.1101/2023.01.17.523348.

Normative modeling of brain morphometry in Clinical High-Risk for Psychosis

Shalaila S Haas¹, Ruiyang Ge^{2

3}, Ingrid Agartz^{4

5

6

7}, G Paul Amminger^{8

9}, Ole A Andreassen^{10

6}, Peter Bachman¹¹, Inmaculada Baeza¹², Sunah Choi¹³, Tiziano Colibazzi^{14

15}, Vanessa L Cropley¹⁶, Camilo de la Fuente-Sandoval¹⁷, Bjørn H Ebdrup^{18

19}, Adriana Fortea²⁰, Paolo Fusar-Poli^{21

22}, Birte Yding Glenthøj^{18

19}, Louise Birkedal Glenthøj²³, Kristen M Haut²⁴, Rebecca A Hayes¹¹, Karsten Heekeren^{25

26}, Christine I Hooker²⁴, Wu Jeong Hwang^{13

27}, Neda Jahanshad²⁸, Michael Kaess^{29

30}, Kiyoto Kasai^{31

32

33}, Naoyuki Katagiri³⁴, Minah Kim^{35

36}, Jochen Kindler³⁰, Shinsuke Koike^{37

32}, Tina D Kristensen³⁸, Jun Soo Kwon^{35

36}, Stephen M Lawrie³⁹, Jimmy Lee^{40

41}, Imke Lj Lemmers-Jansen^{42

43}, Ashleigh Lin⁴⁴, Xiaoqian Ma⁴⁵, Daniel H Mathalon^{46

47}, Philip McGuire⁴⁸, Chantal Michel³⁰, Romina Mizrahi^{49

50}, Masafumi Mizuno⁵¹, Paul Møller⁵², Ricardo Mora-Durán⁵³, Barnaby Nelson^{8

9}, Takahiro Nemoto³⁴, Merete Nordentoft²³, Dorte Nordholm²³, Maria A Omelchenko⁵⁴, Christos Pantelis^{55

56}, Jose C Pariente⁵⁷, Jayachandra M Raghava^{18

58}, Francisco Reyes-Madrigal¹⁷, Jan I Røssberg⁵⁹, Wulf Rössler^{60

61}, Dean F Salisbury⁶², Daiki Sasabayashi^{63

64}, Ulrich Schall^{65

66}, Lukasz Smigielski^{67

26}, Gisela Sugranyes¹², Michio Suzuki^{63

64}, Tsutomu Takahashi^{63

64}, Christian K Tamnes^{4

7

68}, Anastasia Theodoridou²⁶, Sophia I Thomopoulos²⁸, Paul M Thompson²⁸, Alexander S Tomyshev⁶⁹, Peter J Uhlhaas^{70

71}, Tor G Værnes^{72

7}, Therese Amj van Amelsvoort⁷³, Theo Gm van Erp^{74

75}, James A Waltz⁷⁶, Christina Wenneberg²³, Lars T Westlye^{77

7

6}, Stephen J Wood^{8

9

78}, Juan H Zhou^{79

80}, Dennis Hernaus⁷³, Maria Jalbrzikowski^{11

81}, René S Kahn¹, Cheryl M Corcoran^{1

82}, Sophia Frangou^{1

2

3}; ENIGMA Clinical High Risk for Psychosis Working Group

Affiliations

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

PMID: 36711551
PMCID: PMC9882206
DOI: 10.1101/2023.01.17.523348

Normative modeling of brain morphometry in Clinical High-Risk for Psychosis

Shalaila S Haas et al. bioRxiv. 2023.

[Preprint]. 2023 Jan 18:2023.01.17.523348.

doi: 10.1101/2023.01.17.523348.

Authors

Affiliations

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

PMID: 36711551
PMCID: PMC9882206
DOI: 10.1101/2023.01.17.523348

Update in

Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis.
ENIGMA Clinical High Risk for Psychosis Working Group; Haas SS, Ge R, Agartz I, Amminger GP, Andreassen OA, Bachman P, Baeza I, Choi S, Colibazzi T, Cropley VL, de la Fuente-Sandoval C, Ebdrup BH, Fortea A, Fusar-Poli P, Glenthøj BY, Glenthøj LB, Haut KM, Hayes RA, Heekeren K, Hooker CI, Hwang WJ, Jahanshad N, Kaess M, Kasai K, Katagiri N, Kim M, Kindler J, Koike S, Kristensen TD, Kwon JS, Lawrie SM, Lebedeva I, Lee J, Lemmers-Jansen ILJ, Lin A, Ma X, Mathalon DH, McGuire P, Michel C, Mizrahi R, Mizuno M, Møller P, Mora-Durán R, Nelson B, Nemoto T, Nordentoft M, Nordholm D, Omelchenko MA, Pantelis C, Pariente JC, Raghava JM, Reyes-Madrigal F, Røssberg JI, Rössler W, Salisbury DF, Sasabayashi D, Schall U, Smigielski L, Sugranyes G, Suzuki M, Takahashi T, Tamnes CK, Theodoridou A, Thomopoulos SI, Thompson PM, Tomyshev AS, Uhlhaas PJ, Værnes TG, van Amelsvoort TAMJ, van Erp TGM, Waltz JA, Wenneberg C, Westlye LT, Wood SJ, Zhou JH, Hernaus D, Jalbrzikowski M, Kahn RS, Corcoran CM, Frangou S. ENIGMA Clinical High Risk for Psychosis Working Group, et al. JAMA Psychiatry. 2024 Jan 1;81(1):77-88. doi: 10.1001/jamapsychiatry.2023.3850. JAMA Psychiatry. 2024. PMID: 37819650 Free PMC article.

Abstract

Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in the majority of individuals at psychosis risk may be nested within the range observed in healthy individuals.

Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high-risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder.

Design setting and participants: Clinical, IQ and FreeSurfer-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1,340 CHR-P individuals [47.09% female; mean age: 20.75 (4.74) years] and 1,237 healthy individuals [44.70% female; mean age: 22.32 (4.95) years] from 29 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group.

Main outcomes and measures: For each regional morphometric measure, z-scores were computed that index the degree of deviation from the normative means of that measure in a healthy reference population (N=37,407). Average deviation scores (ADS) for CT, SA, SV, and globally across all measures (G) were generated by averaging the respective regional z-scores. Regression analyses were used to quantify the association of deviation scores with clinical severity and cognition and two-proportion z-tests to identify case-control differences in the proportion of individuals with infranormal (z<-1.96) or supranormal (z>1.96) scores.

Results: CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z-scores, and all ADS vales. The proportion of CHR-P individuals with infranormal or supranormal values in any metric was low (<12%) and similar to that of healthy individuals. CHR-P individuals who converted to psychosis compared to those who did not convert had a higher percentage of infranormal values in temporal regions (5-7% vs 0.9-1.4%). In the CHR-P group, only the ADS_SA showed significant but weak associations (|β|<0.09; P_FDR<0.05) with positive symptoms and IQ.

Conclusions and relevance: The study findings challenge the usefulness of macroscale neuromorphometric measures as diagnostic biomarkers of psychosis risk and suggest that such measures do not provide an adequate explanation for psychosis risk.

Keywords: FreeSurfer; IQ; MRI; clinical high-risk; normative modeling; positive symptoms.

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Figures

**Figure 1.. Distribution of hippocampal subcortical volume normative z-scores in the study sample.**
The figure presents the distribution of the left and right hippocampus regional normative z-scores in healthy individuals (HI), individuals at clinical high-risk for psychosis (CHR-P) and CHR-P that converted to full-blown psychosis (CHR-PC). The results for the remaining regional normative z-score are presented in the eVideo. The dotted lines represent the cutoffs for infranormal and supranormal values at z = |1.96|.

**Figure 2.. Percentage of subjects with infra- or supranormal regional normative z-scores.**
The proportion of healthy individuals, clinical high-risk for psychosis (CHR-P), and cinical high-risk for psychosis converters with infranormal (left) and supranormal deviations (right) are presented for each hemisphere for cortical thickness, cortical surface area, and subcortical volume.

**Figure 3.. Distribution of the total number of regions with infra- or supranormal regional normative z-scores.**
Bar plots show the distribution of the total number of regions per individual with infra-normal (top row) and supra-normal (bottom row) deviations from the normative model for A) cortical thickness, B) cortical surface area, and C) subcortical volume separately in healthy individuals, clinical high-risk for psychosis (CHR-P) individuals, and clinical high-risk for psychosis converters (CHR-PC).

**Figure 4.. Distributions of average deviation scores and percentage of subjects with infra- or supranormal regional normative z-scores.**
A) Percentage of healthy, clinical high-risk for psychosis (CHR-P), and clinical high-risk for psychosis converters (CHR-PC) with supra- or infranormal global average deviation score (ADS_G), the average deviation score for cortical thickness (ADS_CT), average deviation score for cortical surface area (ADS_SA), and average deviation score for subcortical volumes (ADS_SV). B) The distributions of the average deviation scores in CHR-P (magenta color), CHR-PC (purple color), and healthy individuals (yellow color) for ADS_G, ADS_CT, ADS_SA, and ADS_SV. The dotted lines represent the cutoffs for infranormal and supranormal values at z = |1.96|.

See this image and copyright information in PMC

References

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DC: American Psychiatric Publishing, 2013.
1. GBD 2019 Mental Disorders Collaborators. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry. 2020;9(2):137–150. doi: 10.1016/S2215-0366(21)00395-3 - DOI - PMC - PubMed
1. Fusar-Poli P, Borgwardt S, Bechdolf A, et al. The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry. 2013;70(1):107–120. doi: 10.1001/jamapsychiatry.2013.269 - DOI - PMC - PubMed
1. Catalan A, Salazar de Pablo G, Aymerich C, et al. Neurocognitive Functioning in Individuals at Clinical High Risk for Psychosis: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2021;78(8):859–67. doi: 10.1001/jamapsychiatry.2021.1290 - DOI - PMC - PubMed
1. Salazar de Pablo G, Radua J, Pereira J, et al. Probability of Transition to Psychosis in Individuals at Clinical High Risk: An Updated Meta-analysis. JAMA Psychiatry. 2021;78(9):970–978. doi: 10.1001/jamapsychiatry.2021.0830 - DOI - PMC - PubMed

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This is a preprint.

Normative modeling of brain morphometry in Clinical High-Risk for Psychosis

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Normative modeling of brain morphometry in Clinical High-Risk for Psychosis

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