Omlor Wolfgang, Rabe Finn, Fuchs Simon, Surbeck Werner, Cecere Giacomo, Huang Gao-Yang, Homan Stephanie, Kallen Nils, Georgiadis Foivos, Spiller Tobias, Seifritz Erich, Weickert Thomas, Bruggemann Jason, Weickert Cynthia, Potkin Steven, Hashimoto Ryota, Sim Kang, Rootes-Murdy Kelly, Quide Yann, Houenou Josselin, Banaj Nerisa, Vecchio Daniela, Piras Fabrizio, Piras Federica, Spalletta Gianfranco, Salvador Raymond, Karuk Andriana, Pomarol-Clotet Edith, Rodrigue Amanda, Pearlson Godfrey, Glahn David, Tomecek David, Spaniel Filip, Skoch Antonin, Kirschner Matthias, Kaiser Stefan, Kochunov Peter, Fan Feng-Mei, Andreassen Ole A, Westlye Lars T, Berthet Pierre, Calhoun Vince D, Howells Fleur, Uhlmann Anne, Scheffler Freda, Stein Dan, Iasevoli Felice, Cairns Murray J, Carr Vaughan J, Catts Stanley V, Di Biase Maria A, Jablensky Assen, Green Melissa J, Henskens Frans A, Klauser Paul, Loughland Carmel, Michie Patricia T, Mowry Bryan, Pantelis Christos, Rasser Paul E, Schall Ulrich, Scott Rodney, Zalesky Andrew, de Bartolomeis Andrea, Barone Annarita, Ciccarelli Mariateresa, Brunetti Arturo, Cocozza Sirio, Pontillo Giuseppe, Tranfa Mario, Di Giorgio Annabella, Thomopoulos Sophia I, Jahanshad Neda, Thompson Paul M, van Erp Theo, Turner Jessica, Homan Philipp
Psychiatric Hospital, University of Zurich, Zurich (Omlor, Rabe, Fuchs, Surbeck, Cecere, Huang, S. Homan, Kallen, Georgiadis, Spiller, Seifritz, Kirschner, P. Homan); Neuroscience Center Zurich, University of Zurich and Swiss Federal Institute of Technology Zurich, Zurich (Huang, P. Homan); Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, NY (T. Weickert, C. Weickert); Edith Collins Centre, Sydney Local Health District, Sydney (Bruggemann); Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior (Potkin, van Erp), and Center for the Neurobiology of Learning and Memory (van Erp), University of California Irvine, Irvine; Department of Pathology of Mental Diseases, National Center of Neurology and Psychiatry, National Institute of Mental Health, Tokyo (Hashimoto); Institute of Mental Health, Singapore (Sim); Psychology Department and Neuroscience Institute, Georgia State University, Atlanta (Rootes-Murdy); School of Psychology, University of New South Wales, Sydney (Quide); Hopitaux Universitaires Henri Mondor, Crétail, France (Houenou); Neuropsychiatry Laboratory, Department of Clinical Neuroscience and Neurorehabilitation, Santa Lucia Foundation IRCCS, Rome (Banaj, Vecchio, Fabrizio Piras, Federica Piras, Spalletta); FIDMAG Sisters Hospitallers Research Foundation, Barcelona, Spain (Salvador, Karuk, Pomarol-Clotet); Department of Psychiatry, Boston Children's Hospital, Harvard Medical School, Boston (Rodrigue, Glahn); Department of Psychiatry, Yale University, New Haven, CT, and Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, CT (Pearlson); National Institute of Mental Health, Klecany, Czech Republic (Tomecek, Spaniel, Skoch); Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals, Geneva (Kirschner, Kaiser); Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore (Kochunov); Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing (Fan); NORMENT Center, Division of Mental Health and Addiction, University of Oslo and Oslo University Hospital, and K.G. Jebsen Center for Neurodevelopment, University of Oslo, Oslo (Andreassen, Westlye, Berthet); Neuroscience Institute (Howells) and Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa (Howells, Uhlmann); Department of Child and Adolescent Psychiatry, Technische Universität Dresden, Dresden, Germany (Uhlmann); SA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Neuroscience Institute, University of Cape Town, Cape Town, South Africa (Scheffler, Stein); Laboratory of Molecular and Translational Psychiatry and Unit of Treatment Resistant Psychosis, Section of Psychiatry, Reproductive and Odontostomatological Sciences, Department of Neuroscience, University of Naples Federico II, Naples (Iasevoli); Neuroscience Research Australia, Sydney (T. Weickert, C. Weickert, Bruggemann, Quide); School of Psychiatry, University of New South Wales, Sydney (T. Weickert, C. Weickert, Bruggemann); Specialty of Addiction Medicine, Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney (Bruggemann); Department of Psychiatry and Behavioral Health, Wexner Medical Center, Ohio State University, Columbus (Turner); Tri-Institutional Center for Translational Research in Neuroimaging and Data Science, Georgia State University, Georgia Institute of Technology, Emory University, Atlanta (Calhoun); School of Biomedical Sciences and Pharmacy (Cairns, Scott), Centre for Brain and Mental Health Research (Cairns, Loughland, Schall), School of Medicine and Public Health, College of Health, Medicine, and Wellbeing (Henskens, Rasser), Priority Research Centre for Health Behaviour (Henskens), and School of Psychological Sciences (Michie), University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute, New Lambton Heights, Australia (Cairns, Loughland, Schall); School of Clinical Medicine, Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney (Carr, Green); Neuroscience Research Australia, Randwick (Carr, Green); Department of Psychiatry, Monash University, Clayton, Australia (Carr); School of Medicine, University of Queensland, Brisbane, Australia (Catts); Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Carlton South, Australia (Di Biase, Klauser, Pantelis, Zalesky); Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston (Di Biase); University of Western Australia, Perth (Jablensky); Hunter Medical Research Institute, Newcastle, Australia (Henskens, Michie); Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences and Monash Biomedical Imaging, Monash University, Clayton, Australia (Klauser); Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland (Klauser); Queensland Brain Institute and Queensland Centre for Mental Health Research, University of Queensland, Brisbane, Australia (Mowry); Florey Institute of Neuroscience and Mental Health, Parkville, Australia (Pantelis); Melbourne School of Engineering, University of Melbourne, Parkville, Australia (Zalesky); Section of Psychiatry, Department of Neuroscience (de Bartolomeis, Barone, Ciccarelli), Department of Advanced Biomedical Sciences (Brunetti, Cocozza, Pontillo, Tranfa), and Department of Electrical Engineering and Information Technology (Pontillo), University Federico II, Naples; ASST Papa Giovanni XXIII, Mental Health Department, Bergamo, Italy (Di Giorgio); Imaging Genetics Center, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles (Thomopoulos, Jahanshad, Thompson).
Am J Psychiatry. 2025 Apr 1;182(4):373-388. doi: 10.1176/appi.ajp.20230806. Epub 2025 Feb 26.
The clinical diversity of schizophrenia is reflected by structural brain variability. It remains unclear how this variability manifests across different gray and white matter features. In this meta- and mega-analysis, the authors investigated how brain heterogeneity in schizophrenia is distributed across multimodal structural indicators.
The authors used the ENIGMA dataset of MRI-based brain measures from 22 international sites with up to 6,037 individuals for a given brain measure. Variability and mean values of cortical thickness, cortical surface area, cortical folding index, subcortical volume, and fractional anisotropy were examined in individuals with schizophrenia and healthy control subjects.
Individuals with schizophrenia showed greater variability in cortical thickness, cortical surface area, subcortical volume, and fractional anisotropy within the frontotemporal and subcortical network. This increased structural variability was mainly associated with psychopathological symptom domains, and the schizophrenia group frequently displayed lower mean values in the respective structural measures. Unexpectedly, folding patterns were more uniform in individuals with schizophrenia, particularly in the right caudal anterior cingulate region. The mean folding values of the right caudal anterior cingulate region did not differ between the schizophrenia and healthy control groups, and folding patterns in this region were not associated with disease-related parameters.
In patients with schizophrenia, uniform folding patterns in the right caudal anterior cingulate region contrasted with the multimodal variability in the frontotemporal and subcortical network. While variability in the frontotemporal and subcortical network was associated with disease-related diversity, uniform folding may indicate a less flexible interplay between genetic and environmental factors during neurodevelopment.
精神分裂症的临床多样性通过大脑结构变异性得以体现。目前尚不清楚这种变异性如何在不同的灰质和白质特征中表现出来。在这项荟萃分析和大型分析中，作者研究了精神分裂症患者大脑的异质性如何分布于多模态结构指标中。
作者使用了来自22个国际研究点基于MRI的大脑测量数据的ENIGMA数据集，针对特定大脑测量指标纳入了多达6037名个体。对精神分裂症患者和健康对照者的皮质厚度、皮质表面积（脑区表面积）、皮质折叠指数、皮质下体积和各向异性分数的变异性和平均值进行了检查。
精神分裂症患者在额颞叶和皮质下网络内的皮质厚度、皮质表面积、皮质下体积和各向异性分数表现出更大的变异性。这种结构变异性增加主要与精神病理症状领域相关，并且精神分裂症组在各自的结构测量中常常显示出较低的平均值。出乎意料的是，精神分裂症患者的折叠模式更为一致，尤其是在右侧尾侧前扣带回区域。右侧尾侧前扣带回区域的平均折叠值在精神分裂症组和健康对照组之间没有差异，并且该区域的折叠模式与疾病相关参数无关。
在精神分裂症患者中，右侧尾侧前扣带回区域的一致折叠模式与额颞叶和皮质下网络中的多模态变异性形成对比。虽然额颞叶和皮质下网络的变异性与疾病相关的多样性有关，但一致的折叠可能表明在神经发育过程中遗传和环境因素之间的相互作用缺乏灵活性。
