Year: 2023
Type: review
Study design: Observational Study
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 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: This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. Main Outcomes and Measures: For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < -1.96) or supranormal (z > 1.96) scores. Results: Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the mean (SD) age was 22.32 (4.95) years. Individuals with CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z scores, and all ADS values. For any given region, the proportion of individuals with CHR-P who had infranormal or supranormal values was low (up to 153 individuals [<11.42%]) and similar to that of healthy individuals (<115 individuals [<9.30%]). Individuals with CHR-P who converted to a psychotic disorder had a higher percentage of infranormal values in temporal regions compared with those who did not convert (7.01% vs 1.38%) and healthy individuals (5.10% vs 0.89%). In the CHR-P group, only the ADS SA was associated with positive symptoms (β = -0.08; 95% CI, -0.13 to -0.02; P = .02 for false discovery rate) and IQ (β = 0.09; 95% CI, 0.02-0.15; P = .02 for false discovery rate). Conclusions and Relevance: In this case-control study, findings suggest that macroscale neuromorphometric measures may not provide an adequate explanation of psychosis risk.
Source: JAMA Psychiatry
Authors: Paul Allen, Helen Baldwin, Cali F Bartholomeusz, Michael WL Chee, Xiaogang Chen, Rebecca E Cooper, Lieuwe de Haan, Holly K Hamilton, Ying He, Wenche ten Velden Hegelstad, Leslie E Horton, Daniela Hubl, Mallory J Klaunig, Alex Koppel, Yoo Bin Kwak, Pablo León-Ortiz, Rachel L Loewy, Patrick McGorry, Lijun Ouyang, Paul E Rasser, Franz Resch, Jason Schiffman, Mikkel E Sørensen, Jinsong Tang, Dennis Velakoulis, Sophia Vinogradov, Hidenori Yamasue, Liu Yuan, Alison R Yung, Shalaila S. Haas, Ruiyang Ge, Ingrid Agartz, G. Paul Amminger, Ole A. Andreassen, Peter Bachman, Inmaculada Baeza, Sunah Choi, Tiziano Colibazzi, Vanessa L. Cropley, Camilo de la Fuente-Sandoval, Bjørn H. Ebdrup, Adriana Fortea, Paolo Fusar-Poli, Birte Yding Glenthøj, Louise Birkedal Glenthøj, Kristen M. Haut, Rebecca A. Hayes, Karsten Heekeren, Christine I. Hooker, Wu Jeong Hwang, Neda Jahanshad, Michael Kaess, Kiyoto Kasai, Naoyuki Katagiri, Minah Kim, Jochen Kindler, Shinsuke Koike, Tina D. Kristensen, Jun Soo Kwon, Stephen M. Lawrie, Irina Lebedeva, Jimmy Lee, Imke L. J. Lemmers-Jansen, Ashleigh Lin, Xiaoqian Ma, Daniel H. Mathalon, Philip McGuire, Chantal Michel, Romina Mizrahi, Masafumi Mizuno, Paul Møller, Ricardo Mora-Durán, Barnaby Nelson, Takahiro Nemoto, Merete Nordentoft, Dorte Nordholm, Maria A. Omelchenko, Christos Pantelis, Jose C. Pariente, Jayachandra M. Raghava, Francisco Reyes-Madrigal, Jan I. Røssberg, Wulf Rössler, Dean F. Salisbury, Daiki Sasabayashi, Ulrich Schall, Lukasz Smigielski, Gisela Sugranyes, Michio Suzuki, Tsutomu Takahashi, Christian K. Tamnes, Anastasia Theodoridou, Sophia I. Thomopoulos, Paul M. Thompson, Alexander S. Tomyshev, Peter J. Uhlhaas, Tor G. Værnes, Therese A. M. J. van Amelsvoort, Theo G. M. van Erp, James A. Waltz, Christina Wenneberg, Lars T. Westlye, Stephen J. Wood, Juan H. Zhou, Dennis Hernaus, Maria Jalbrzikowski, René S. Kahn, Cheryl M. Corcoran, Sophia Frangou
Institutions: Icahn School of Medicine at Mount Sinai, University of British Columbia, Djavad Mowafaghian Centre for Brain Health, University of Oslo, Region Stockholm, Karolinska Institutet, Diakonhjemmet Hospital, Stockholm Health Care Services, The University of Melbourne, Orygen, Oslo University Hospital, Boston Children's Hospital, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, Hospital Clínic de Barcelona, Fundació Clínic per a la Recerca Biomèdica, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Seoul National University, New York State Psychiatric Institute, Columbia University, Western Health, Instituto Nacional de Neurología y Neurocirugía, University of Copenhagen, King's College London, University of Pavia, Rush University Medical Center, University of Zurich, LVR-Klinik Köln, Psychiatrische Universitätsklinik Zürich, Catholic Kwandong University, University of Southern California, University of Bern, Heidelberg University, The University of Tokyo Institutes for Advanced Study, International Research Center for Neurointelligence, The University of Tokyo, The University of Tokyo, Toho University, Seoul National University Hospital, Glostrup Hospital, Copenhagen University Hospital, University of Edinburgh, Mental Health Research Center of Russian Academy of Medical Sciences, Nanyang Technological University, Institute of Mental Health, Vrije Universiteit Amsterdam, The Kids Research Institute Australia, The University of Western Australia, Second Xiangya Hospital of Central South University, San Francisco VA Medical Center, University of California, San Francisco, San Francisco VA Health Care System, University of Oxford, McGill University, Tokyo Metropolitan Matsuzawa Hospital, Drammen Hospital, Vestre Viken Hospital Trust, Florey Institute of Neuroscience and Mental Health, Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer, Charité – Universitätsmedizin Berlin, University of Pittsburgh, University of Toyama, Research Center for Idling Brain Science, University of Toyama, University of Newcastle Australia, University of Glasgow, Maastricht University, University of California, Irvine, University of Maryland, Baltimore, University of Birmingham, National University of Singapore, Harvard University, James J. Peters VA Medical Center
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: U.S. Department of Veterans Affairs, University of Southern California, University of Pittsburgh, Fundación Alicia Koplowitz, McGill University, Rush University, University of Bern, Japan Agency for Medical Research and Development, Korea Brain Research Institute, National Institute for Health and Care Research, King's College London, University of Oxford, European Commission, University of Glasgow, National Research Foundation, National University of Singapore, Nanyang Technological University, Universität Heidelberg, Vrije Universiteit Amsterdam, Universiteit Maastricht, Seoul National University, Central South University, Gentofte Hospital, Consejo Nacional de Ciencia y Tecnología, Lundbeckfonden, National Research Foundation of Korea, Seoul National University Hospital, University of Tokyo, Università degli Studi di Pavia, Universitetet i Oslo, Universitat de Barcelona, Universität Zürich, Faculty of Health and Medical Sciences, University of Western Australia, Universitätsspital Zürich, Catholic Kwandong University, H. Lundbeck A/S, National Institutes of Health, University of California, San Francisco, University of California, Irvine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, Department of Psychiatry, Columbia University, College of Medicine, Seoul National University, Canadian Institutes of Health Research, Medical Research Council, National Health and Medical Research Council, National Medical Research Council, Japan Society for the Promotion of Science, Japan Science and Technology Agency, Instituto de Salud Carlos III, Det Sundhedsvidenskabelige Fakultet, Københavns Universitet, Lee Kong Chian School of Medicine, Nanyang Technological University, Xiangya Hospital, Central South University, National Institute of Mental Health, National Institute of Biomedical Imaging and Bioengineering, NIH Clinical Center, National Center for Advancing Translational Sciences, Moonshot Research and Development Program
Awards: Marcadores de disfunción glutamatérgica en adolescentes con alto riesgo de psicosis: relación con estructura cerebral, sintomatología y metabolismo oxidativo, An attempt to predict prognosis of psychotic disorders by a combination of biomarkers, ENIGMA-SD: Understanding Sex Differences in Global Mental Health through ENIGMA, 複雑臓器制御系の数理的包括理解と超早期精密医療への挑戦, G1793114910, Thought disorder and social cognition in clinical risk states for schizophrenia, Imaging Neuroinflammation in Clinical high risk and Schizophrenia, G2148141080, G2238785707, G2404417979, G2568858748, Running in the FAMILY - Understanding and predicting the intergenerational transmission of mental illness, G2620658983, Investigating neuroinflammation and its relationship with progressive brain structural loss in schizophrenia, 早期精神病におけるマルチモダル脳指標は認知機能軌跡を予測するか：アジア多施設研究, ENIGMA-COINSTAC: Advanced Worldwide Transdiagnostic Analysis of Valence System Brain Circuit, Neurodevelopmental variation of intrinsic functional connectivity and its relationship to psychosis risk and gene expression, G2922334509, G3010482402, G3051627418, G3133665439, G3302461048, G3326939414, G3414204190, Estudio longitudinal sobre marcadores nutricionales y de estrés en niños y adolescentes con síndrome de riesgo de psicosis y su capacidad predictiva de la transición a psicosis, Reward System Function as a Potential Mediator of the Impact of Stress on Psychopathology: A Computational Neuroimaging Study, Refining the synaptic pruning hypothesis of psychosis in humans, G4345613377, G4379248823, Developing Novel Preclinical Models for Neurodevelopmental Disorders - From Bedside to Bench, Optimizing Cognitive Training to Improve Functional Outcome in Clinical High Risk, G4565001412, G4718590172, Translating membrane proteins into therapeutics; from bedside to bench, G4929831872, G5064927929, G5368403867, G5381923993, G5484820199, Functional Brain Abnormalities in the Schizophrenia Prodrome, G5965467150, ENIGMA Center for Worldwide Medicine, Imaging & Genomics, Imaging Alterations in Endocannabinoid Metabolism in Clinical High Risk and First Episode Psychosis, Improving the mental health of trans and gender diverse young people, Estudio multicéntrico longitudinal sobre el papel de marcadores neurobiológicos de estrés en niños y adolescentes con síndrome de riesgo de psicosis y la transición a psicosis, Construcción de un modelo multimodal con capacidad diagnóstica y pronóstica en adolescentes con alto riesgo de psicosis: integración de factores genéticos, ambientales y de neuroimagen., G6687757193, G6758941665, G6762535340, Longitudinal imaging in adolescents prodromal for schizophrenia, G7034732238, Redefine Trans-Neuropsychiatric Disorder Brain Patterns through Big-Data and Machine Learning, G7467997106, Auditory Cortex Connectivity in Emerging Psychosis, Toward reconstructing psychiatric disorders based on brain structure and function: International joint research project, Characterization of subcortical structures in clinical high-risk state for psychosis using Japanese multicenter data toward clinical application, Can We Predict Psychosis and Can It Be Prevented?, Mechanisms of copper dysregulation in schizophrenia, G8587457205, Translational research using neural oscillation in schizophrenia: Toward elucidating pathogenesis and developing novel therapeutic approaches, Prediction of clinical outcome by multimodal probability model in young patients with psychiatric disorders, G8860921842, Using the RDoC Approach to Understand Thought Disorder: A Linguistic Corpus-Based Approach, G8934710651, G9000048348, G9000171045, Research Training in Mood and Anxiety Disorders: From Animal Models to Patients, Conduits: Mount Sinai Health System Translational Science Hub, Predicting psychosis risk in youth using a novel structural neuroimaging score that measures deviation from normative development. Can we bring it to communities using portable, low-field MRI?, Training the next generation of clinical neuroscientists, G941506662
OpenAlex ID: W4387540596