特定恐惧症及其动物和血液-注射-伤害亚型的皮质和皮质下脑改变：来自 ENIGMA 焦虑工作组的 Mega 分析。
Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group.
机构信息
Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany (Hilbert, Boeken, Langhammer, Fehm, Lueken); Department of Psychology, Health and Medical University Erfurt, Erfurt, Germany (Hilbert); German Center for Mental Health, Partner Site Berlin/Potsdam, Berlin, Germany (Lueken); Neuroscience Institute, Department of Psychiatry and Mental Health, University of Cape Town, and South African Medical Research Council Unit on Child and Adolescent Health, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa (Groenewold); Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands (Bas-Hoogendam, Van der Wee); Department of Developmental and Educational Psychology, Institute of Psychology, Leiden University, Leiden, the Netherlands (Bas-Hoogendam); Leiden Institute for Brain and Cognition, Leiden, the Netherlands (Bas-Hoogendam, Van der Wee); Forensic Family and Youth Care Studies, Institute of Education and Child Studies, Leiden University, Leiden, the Netherlands (Aghajani); Department of Psychiatry, Amsterdam UMC location VUMC, Amsterdam (Aghajani, Veltman); Emotion and Development Branch, NIMH, Bethesda, Md. (Zugman, Harrewijn, Pine); Department of Psychology and Social Work, Mid Sweden University, Östersund, Sweden (Åhs); Institute for Translational Psychiatry (Arolt, Böhnlein, Dannlowski, Grotegerd, Leehr, Schrammen), Institute of Medical Psychology and Systems Neuroscience (Hofmann, T. Straube), and University Clinic for Radiology (Kugel), University of Münster, Münster, Germany; Institute for Clinical Psychology and Psychotherapy, Behavioral Epidemiology, Technische Universität Dresden, Dresden, Germany (Beesdo-Baum); Department of Psychology, Lund University, Lund, Sweden (Björkstrand); Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha (Blackford); MRI Research Unit, Department of Radiology, Hospital del Mar, and IMIM-CIBER de Salud Mental, Instituto de Salud Carlos III, Barcelona, Spain (Blanco-Hinojo, Pujol); Institute of Diagnostic Radiology and Neuroradiology (Bülow), Department of Psychiatry and Psychotherapy (Grabe, Wittfeld), Functional Imaging Unit, Diagnostic Radiology and Neuroradiology (Lotze), and Institute for Community Medicine (Völzke), University Medicine Greifswald, Greifswald, Germany; Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain (Cano, Cardoner); Department of Psychiatry and Forensic Medicine, Universitat Autonòma de Barcelona, Barcelona, Spain (Cardoner); Centro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Madrid (Cano, Cardoner); Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (Cardoner); Department of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Caseras); Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (Domschke); Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tenn. (Feola); Department of Psychology, Uppsala University, Uppsala, Sweden (Fredrikson); Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, the Netherlands (Goossens, Schruers); German Center for Neurodegenerative Diseases, Site Rostock/Greifswald, Greifswald, Germany (Grabe); Department of Psychiatry, University of Pennsylvania, Philadelphia (Gur, Satterthwaite); Department of Biological and Clinical Psychology, University of Greifswald, Greifswald, Germany (Hamm, Richter); Department of Psychology, Education, and Child Studies, Erasmus University Rotterdam, Rotterdam, the Netherlands (Harrewijn); Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany (Heinig, Leonhardt, J. Schäfer); Department of Psychiatry, Psychosomatics, and Psychotherapy, Center of Mental Health, University Hospital Würzburg, Würzburg, Germany (Herrmann); Interdisciplinary Laboratory of Clinical Neuroscience and Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil (Jackowski, Pan); Department of Pediatrics, Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis (Larsen); Core-Facility Brain Imaging, Faculty of Medicine (Jansen), and Department of Psychiatry (Krug, Nenadić, F. Stein), University of Marburg, Marburg, Germany; Department of Psychology, Vanderbilt University, Nashville, Tenn. (Kaczkurkin); Department of Psychology, University of Amsterdam, Amsterdam (Kindt, Visser); COMIC Research, Leeds and York Partnership NHS Foundation Trust, Leeds, U.K. (Kingsley); Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden (Klahn); LVR-University Hospital Essen, Department of Psychiatry and Psychotherapy, Faculty of Medicine, and Center for Translational Neuro- and Behavioral Sciences, University of Duisburg-Essen, Essen, North Rhine-Westphalia, Germany (Koelkebeck); Department of Psychiatry, University Hospital of Bonn, Bonn, Germany (Krug); Mental Health Research and Treatment Center, Faculty of Psychology, Ruhr-Universität Bochum, Bochum, Germany (Margraf); Laboratory of Affective Neuroscience in Poznan, SWPS University, Warsaw, Poland (Michałowski); Department of Psychology, Faculty of Human Sciences, and Institute for Cognitive and Affective Neuroscience, Medical School Hamburg, Hamburg, Germany (Muehlhan); Department of Psychology, University of Würzburg, Würzburg, Germany (Pauli, Schulz, Wiemer); Department of Clinical Psychology, Psychobiology, and Methodology, Universidad de La Laguna, San Cristóbal de La Laguna, Spain (Peñate, Rivero); Translational Psychotherapy, Institute of Psychology, University of Göttingen, Göttingen, Germany (Pittig); Department of Medicine, Health and Medical University, Potsdam, Germany (Plag); Department of Experimental Psychopathology, University of Hildesheim, Hildesheim, Germany (Richter); Department of Psychology, Faculty of Health Science, Universidad Europea de Canarias, La Orotava, Spain (Rivero); Section on Negative Affect and Social Processes, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (Salum); Department of Psychology (A. Schäfer) and Department of Psychotherapy and Systems Neuroscience (Stark), Bender Institute of Neuroimaging, Justus Liebig University Giessen, and Center for Mind, Brain, and Behavior, Universities of Marburg and Giessen (A. Schäfer, Stark), Giessen, Germany; Department of Psychology, University of Graz, Graz, Austria (Schienle, Wabnegger); Clinical Child and Adolescent Psychology, Mental Health Research and Treatment Center, Faculty of Psychology, Ruhr-Universität Bochum, Bochum, Germany (Schneider); Department of Behavioral Medicine and Principles of Human Biology for the Health Sciences, Universität Trier, Trier, Germany (Schulz); Research Group Security and Privacy, Faculty of Computer Science, University of Vienna, Vienna (Seidl); Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany (Kircher, B. Straube, Yang); Department of Psychiatry and Neuroscience, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany (Ströhle); Department of Psychology, Ruhr-Universität Bochum, Bochum, Germany (Suchan, Wannemüller); Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey (Thomopoulos, Jahanshad, Thompson); Department of Biological Psychology and Affective Science, Faculty of Human Sciences, University of Potsdam, Potsdam, Germany (Ventura-Bort, Wendt); Health Sciences, University of York, York, U.K. (Wright); Department of Psychiatry and Behavioral Sciences, University of Minnesota Medical School, Minneapolis (Zilverstand); KBO-Inn-Salzach-Klinikum, Wasserburg am Inn, Germany (Zwanzger); Department of Psychiatry and Psychotherapy, Ludwig Maximilians University of Munich, Munich, Germany (Zwanzger); Division of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Brownsville (Winkler); South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Neuroscience Institute, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa (D.J. Stein); Department of Education, Information, and Communications Technology and Learning, Østfold University College, Halden, Norway (Jackowski).
出版信息
Am J Psychiatry. 2024 Aug 1;181(8):728-740. doi: 10.1176/appi.ajp.20230032. Epub 2024 Jun 11.
OBJECTIVE
Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults).
METHODS
Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis.
RESULTS
Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents.
CONCLUSIONS
Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.
目的
特定恐惧症是一种常见的焦虑障碍，但与相关脑结构改变的文献存在很大差距。ENIGMA 焦虑工作组研究了特定恐惧症患者与健康对照组之间，以及动物恐惧症和血液注射损伤（BII）特定恐惧症亚型之间的大脑结构差异。此外，作者还研究了大脑结构与症状严重程度和年龄（青少年与成年人）的关系。
方法
合并了 31 项原始研究的数据，创建了一个最终样本，其中包括 1452 名恐惧症患者和 2991 名健康参与者（62.7%为女性；年龄 5-90 岁）。使用既定的 ENIGMA 协议进行成像处理和质量控制。在预先注册的分析中检查了皮质下体积以及皮质表面积和厚度。
结果
与健康对照组相比，恐惧症组的皮质下体积普遍较小，表面差异混合，大量区域的皮质厚度较大。恐惧症亚组也表现出差异，包括如假设的那样，BII 恐惧症（N=182）的内侧眶额皮质厚度大于动物恐惧症（N=739）。所有发现都由成年参与者驱动；在儿童和青少年中未观察到显著结果。
结论
与其他焦虑障碍的可比分析相比，与特定恐惧症相关的大脑改变在程度和效应大小上都超过了其他焦虑障碍，并且不限于大脑结构的减少。此外，恐惧症亚组之间的现象学差异反映在不同的神经基础上，包括与恐惧处理和更高认知过程相关的大脑区域。这些发现表明特定恐惧症存在大脑结构改变，尽管特别是皮质下改变可能也与更广泛的内化性精神病理学有关。
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