Brain Aging in Specific Phobia: An ENIGMA-Anxiety Mega-Analysis
medRxiv, vol. 47, pp. e70595
Abstract
Introduction Specific phobia (SPH) is a prevalent anxiety disorder and may involve advanced biological aging. However, brain age research in psychiatry has primarily examined mood and psychotic disorders. This mega-analysis investigated brain aging in SPH participants within the ENIGMA-Anxiety Working Group. Methods 3D brain s tructural MRI scans from 17 international samples (600 SPH individuals, of whom 504 formally diagnosed and 96 questionnaire-based cases; 1,134 controls; age range: 22-75 years) were processed with FreeSurfer. Brain age was estimated from 77 subcortical and cortical regions with a publicly available ENIGMA brain age model. The brain-predicted age difference (brain-PAD) was calculated as brain age minus chronological age. Linear mixed-effect models examined group differences in brain-PAD and moderation by age. Results No significant group difference in brain-PAD manifested ( β diagnosis (SE)=0.37 years (0.43), p =0.39). A negative diagnosis-by-age interaction was identified, which was most pronounced in formally diagnosed SPH ( β diagnosis-by-age =-0.08 (0.03), pFDR =0.02). This interaction remained significant when excluding participants with anxiety comorbidities, depressive comorbidities, and medication use. Post-hoc analyses revealed a group difference for formal SPH diagnosis in younger participants (22-35 years; β diagnosis =1.20 (0.60), p <0.05, mixed-effects d (95% confidence interval)=0.14 (0.00-0.28)), but not older participants (36-75 years; β diagnosis =0.07 (0.65), p =0.91). Conclusions Brain aging did not relate to SPH in the full sample. However, a diagnosis-by-age interaction was observed across analyses, and was strongest in formally diagnosed SPH. Post-hoc analyses showed a subtle advanced brain aging in young adults with formally diagnosed SPH. Taken together, these findings indicate the importance of clinical severity, impairment and persistence, and may suggest a slightly earlier end to maturational processes or subtle decline of brain structure in SPH.
Authors 73
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Kimberly V. Blake corresponding
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Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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HMU Health and Medical University Erfurt
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Department of Psychology, Health and Medical University Erfurt, Erfurt, Germany
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Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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The University of Melbourne · Orygen
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Centre for Youth Mental Health, University of Melbourne, Orygen, Parkville, VIC, Australia
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Janna Marie Bas‐Hoogendam Aachen Department of Developmental and Educational Psychology Leiden University Department of Psychiatry, Leiden University Medical Center Leiden Institute for Brain and Cognition
Leiden University · Leiden University Medical Center
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Department of Developmental and Educational Psychology Leiden University, Leiden, The Netherlands
Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden, The Netherlands
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Department of Psychology and Social Work, Mid Sweden University, Östersund, Sweden
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University of Münster · University Hospital Münster
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University Clinic for Radiology, University of Münster, Münster, Germany
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Technische Universität Dresden
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Behavioral Epidemiology, Institute of Clinical Psychology and Psychotherapy, TUD - Dresden University of Technology, Dresden, Germany
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Department of Psychology, Lund University, Lund, Sweden
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MRI Research Unit, Department of Radiology, Hospital del Mar, Barcelona, Spain
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Institute for Translational Psychiatry, University of Münster, Münster, Germany
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Universitätsmedizin Greifswald · Universität Greifswald
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Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany
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Hospital de Sant Pau · Institut de Recerca Sant Pau
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Sant Pau Mental Health Research Group, Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain
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Hospital de Sant Pau · Institut de Recerca Sant Pau
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Sant Pau Mental Health Research Group, Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain
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Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, Wales
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Institute for Translational Psychiatry, University of Münster, Münster, Germany
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Department of Psychology, Uppsala University, Uppsala, Sweden
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Maastricht University Medical Centre · Maastricht University
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Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, The Netherlands
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Universitätsmedizin Greifswald · Universität Greifswald
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Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
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Institute for Translational Psychiatry, University of Münster, Münster, Germany
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Institute for Translational Psychiatry, University of Münster, Münster, Germany
12. Institute for Translational Psychiatry, University of Münster, Münster, Germany
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Institute of Psychology, University of Greifswald, Greifswald, Germany
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Technische Universität Dresden
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Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany
20. Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany
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University of Würzburg · Universitätsklinikum Würzburg
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Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, Würzburg, Germany
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Philipps University of Marburg
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Center for Mind, Brain and Behavior (CMBB), Marburg, Germany
Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
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Philipps University of Marburg
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Center for Mind, Brain and Behavior (CMBB), Marburg, Germany
Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
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University of Amsterdam, Amsterdam, The Netherlands
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Philipps University of Marburg
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Center for Mind, Brain and Behavior (CMBB), Marburg, Germany
Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
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Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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LVR-University Hospital Essen, Medical Faculty, Department of Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany
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Philipps University of Marburg
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Center for Mind, Brain and Behavior (CMBB), Marburg, Germany
Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
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Institute for Translational Psychiatry, University of Münster, Münster, Germany
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Universitätsmedizin Greifswald · Universität Greifswald
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Functional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany
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Mental Health Research and Treatment Center, Ruhr-Universitaet Bochum, Bochum, Germany
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MSH Medical School Hamburg – University of Applied Sciences and Medical University
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Department of Psychology, Faculty of Human Sciences, MSH Medical School Hamburg, Hamburg, Germany
ICAN Institute of Cognitive and Affective Neuroscience, MSH Medical School Hamburg, Hamburg, Germany
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Philipps University of Marburg
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Center for Mind, Brain and Behavior (CMBB), Marburg, Germany
Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
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Department of Clinical Psychology, Psychobiology and Methodology, University of La Laguna, La Laguna, Spain
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Translational Psychotherapy, Institute of Psychology, University of Göttingen, Göttingen, Germany
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HMU Health and Medical University
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Faculty of Medicine, Institute for Mental Health and Behavioral Medicine, HMU Health and Medical University Potsdam, Potsdam, Germany
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MRI Research Unit, Department of Radiology, Hospital del Mar, Barcelona, Spain
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Institute of Psychology, University of Hildesheim, Hildesheim, Germany
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Philipps University of Marburg
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Center for Mind, Brain and Behavior (CMBB), Marburg, Germany
Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
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Universidad Europea de Canarias
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Universidad Europea de Canarias, La Orotava, Spain
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Philipps University of Marburg · Justus-Liebig-Universität Gießen
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Bender Institute of Neuroimaging, Justus Liebig University Giessen, Giessen, Germany
Center for Mind, Brain and Behavior, Philipps-University Marburg, Marburg, Germany
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Technische Universität Dresden
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Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany
20. Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany
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University of Graz, Graz, Austria
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Institute for Translational Psychiatry, University of Münster, Münster, Germany
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Maastricht University Medical Centre · Maastricht University
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Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, The Netherlands
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SBA Research, Vienna, Austria
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Justus-Liebig-Universität Gießen
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Department of Psychotherapy and Systems Neuroscience, Justus Liebig University Giessen, Giessen, Germany
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Philipps University of Marburg
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Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany
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University of Würzburg · Universitätsklinikum Würzburg
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Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, Würzburg, Germany
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Stiftung Charité · Charité - Universitätsmedizin Berlin
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Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany
Department of Psychiatry and Psychotherapy, Campus Charitè Mitte, Charitè - Universitätsmedizin Berlin, Berlin, Germany
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Philipps University of Marburg
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Center for Mind, Brain and Behavior (CMBB), Marburg, Germany
Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
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University of Southern California
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Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, California, CA, USA
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Department of Psychology, University of Potsdam, Potsdam, Germany
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University of Amsterdam, Amsterdam, The Netherlands
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Universitätsmedizin Greifswald · Universität Greifswald
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Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
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University of Graz, Graz, Austria
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Department of Biological Psychology and Affective Science, Faculty of Human Sciences, University of Potsdam, Potsdam, Germany
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Ludwig-Maximilians-Universität München
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Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany
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Universitätsmedizin Greifswald · Universität Greifswald
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Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
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Department of Experimental Psychopathology, Institute for Psychology, Hildesheim University, Hildesheim, Germany
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Department of Psychiatry & Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA
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Ludwig-Maximilians-Universität München
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Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University of Munich, Munich, Germany
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The University of Melbourne · Orygen
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Centre for Youth Mental Health, University of Melbourne, Orygen, Parkville, VIC, Australia
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Institute of Education & Child Studies, Section Forensic Family & Youth Care, Leiden University, Leiden, The Netherlands
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National Institute of Mental Health
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Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA
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University of Southern California
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Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, California, CA, USA
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Nic J.A. van der Wee Aachen Department of Psychiatry, Leiden University Medical Center Leiden Institute for Brain and Cognition
Leiden University · Leiden University Medical Center
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Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden, The Netherlands
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Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa
SA-MRC Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa
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Humboldt-Universität zu Berlin · Deutsches Zentrum für Psychische Gesundheit
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Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany
German Center for Mental Health (DZPG), partner site Berlin/Potsdam, Germany
55. Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany
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Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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