Brain Aging in Specific Phobia: An ENIGMA ‐Anxiety Mega‐Analysis
Human Brain Mapping, vol. 47
Abstract
ABSTRACT Specific phobia (SPH) is a prevalent anxiety disorder and may involve advanced biological aging. However, limited brain age research has been conducted in anxiety disorders. This mega‐analysis investigated brain aging in SPH participants within the ENIGMA‐Anxiety Working Group. 3D brain structural MRI scans from 17 international samples (600 SPH individuals, of whom 504 formally diagnosed and 96 questionnaire‐based cases; 1134 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‐effects models examined group differences in brain‐PAD and moderation by age. 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). 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 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 76
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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 HMU 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 Victoria Australia
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Janna Marie Bas‐Hoogendam Aachen 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
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 Dresden University of Technology (TUD) 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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Department for Clinical Psychology and Translational Psychotherapy University of Münster Münster Germany
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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Sant Pau Mental Health Research Group Barcelona Spain
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Sant Pau Mental Health Research Group Barcelona Spain
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Centre for Neuropsychiatric Genetics and Genomics Cardiff University Cardiff UK
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Bielefeld University · Deutsches Zentrum für Psychische Gesundheit
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Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C‐I‐R‐C), site Jena Magdeburg Germany
Department of Psychiatry Medical School and University Medical Center OWL, Protestant Hospital of the Bethel Foundation, Bielefeld University Bielefeld Germany
German Center for Mental Health (DZPG), site Jena Magdeburg 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
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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 Germany
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Department of Psychiatry, Psychosomatics and Psychotherapy University Hospital Würzburg Würzburg Germany
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Institute of Medical Psychology and Systems Neuroscience University of Münster Münster Germany
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Philipps University of Marburg
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Center for Mind, Brain and Behavior (CMBB), Marburg 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 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 Marburg Germany
Department of Psychiatry and Psychotherapy University of Marburg Marburg Germany
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Affiliation as printed
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy University of Gothenburg Gothenburg Sweden
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Medical School and University Medical Center OWL, Protestant Hospital of the Bethel Foundation, Department of Psychiatry and Psychotherapy Bielefeld University Bielefeld Germany
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Department of Psychiatry and Psychotherapy University Hospital Bonn Bonn 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 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 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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Department of Experimental Psychopathology, Institute for Psychology Hildesheim University Hildesheim Germany
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Philipps University of Marburg
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Center for Mind, Brain and Behavior (CMBB), Marburg 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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Behavioral Epidemiology, Institute of Clinical Psychology and Psychotherapy Dresden University of Technology (TUD) Dresden Germany
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University of 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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Institute of Medical Psychology and Systems Neuroscience University of Münster Münster Germany
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Charité - Universitätsmedizin Berlin
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Department of Psychiatry and Psychotherapy, Campus Charité Mitte Charité ‐ Universitätsmedizin Berlin Berlin Germany
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Neuropsychological Therapy Centre, Faculty of Psychology Ruhr University Bochum Bochum Germany
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Philipps University of Marburg
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Center for Mind, Brain and Behavior (CMBB), Marburg 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 Los Angeles California 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 Austria
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University of Amsterdam Amsterdam the Netherlands
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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 Minnesota 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 Victoria Australia
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Moji Aghajani Aachen Institute of Education and Child Studies Section Forensic Family & Youth Care Leiden University Leiden The Netherlands
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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 Maryland 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 Los Angeles California USA
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Nic JA van der Wee Aachen Department of Psychiatry Leiden University Medical Center Leiden The Netherlands Leiden Institute for Brain and Cognition Leiden The Netherlands
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 Germany
German Center for Mental Health (DZPG), partner site Berlin/Potsdam Berlin and Potsdam 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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