Brain Aging in Specific Phobia: An ENIGMA-Anxiety Mega-Analysis.
Authors
Affiliations (61)
Affiliations (61)
- Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
- Department of Psychology, HMU Health and Medical University Erfurt, Erfurt, Germany.
- Centre for Youth Mental Health, University of Melbourne, Orygen, Parkville, Victoria, Australia.
- 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.
- Department of Psychology and Social Work, Mid Sweden University, Östersund, Sweden.
- University Clinic for Radiology, University of Münster, Münster, Germany.
- Behavioral Epidemiology, Institute of Clinical Psychology and Psychotherapy, Dresden University of Technology (TUD), Dresden, Germany.
- Department of Psychology, Lund University, Lund, Sweden.
- MRI Research Unit, Department of Radiology, Hospital del Mar, Barcelona, Spain.
- Institute for Translational Psychiatry, University of Münster, Münster, Germany.
- Department for Clinical Psychology and Translational Psychotherapy, University of Münster, Münster, Germany.
- Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
- Sant Pau Mental Health Research Group, Barcelona, Spain.
- Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
- 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.
- Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), site Jena, Magdeburg, Germany.
- Department of Psychology, Uppsala University, Uppsala, Sweden.
- Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, the Netherlands.
- Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
- Institute of Psychology, University of Greifswald, Greifswald, Germany.
- Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Germany.
- Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, Würzburg, Germany.
- Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany.
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
- Center for Mind, Brain and Behavior (CMBB), Marburg, Marburg, Germany.
- University of Amsterdam, Amsterdam, the Netherlands.
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- Medical School and University Medical Center OWL, Protestant Hospital of the Bethel Foundation, Department of Psychiatry and Psychotherapy, Bielefeld University, Bielefeld, Germany.
- Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany.
- Functional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
- Mental Health Research and Treatment Center, Ruhr-Universitaet Bochum, Germany.
- 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.
- Department of Clinical Psychology, Psychobiology and Methodology, University of La Laguna, La Laguna, Spain.
- Translational Psychotherapy, Institute of Psychology, University of Göttingen, Göttingen, Germany.
- Faculty of Medicine, Institute for Mental Health and Behavioral Medicine, HMU Health and Medical University Potsdam, Potsdam, Germany.
- Department of Experimental Psychopathology, Institute for Psychology, Hildesheim University, Hildesheim, Germany.
- Universidad Europea de Canarias, La Orotava, Spain.
- Bender Institute of Neuroimaging, Justus Liebig University Giessen, Giessen, Germany.
- Center for Mind, Brain and Behavior, Philipps-University Marburg, Marburg, Germany.
- University of Graz, Austria.
- SBA Research, Vienna, Austria.
- Department of Psychotherapy and Systems Neuroscience, Justus Liebig University Giessen, Giessen, Germany.
- Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
- Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany.
- Neuropsychological Therapy Centre, Faculty of Psychology, Ruhr University Bochum, Bochum, Germany.
- Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
- Department of Psychology, University of Potsdam, Potsdam, Germany.
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
- Department of Biological Psychology and Affective Science, Faculty of Human Sciences, University of Potsdam, Potsdam, Germany.
- Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany.
- Department of Psychiatry & Behavioral Sciences, University of Minnesota, Minneapolis, Minnesota, USA.
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University of Munich, Munich, Germany.
- Institute of Education & Child Studies, Section Forensic Family & Youth Care, Leiden University, Leiden, the Netherlands.
- Emotion and Development Branch, National Institute of Mental Health, Bethesda, Maryland, USA.
- SA-MRC Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.
- Department of Psychology, Humboldt-Universität zu Berlin, Germany.
- German Center for Mental Health (DZPG), partner site Berlin/Potsdam, Berlin and Potsdam, Germany.
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<sub>diagnosis</sub> [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<sub>diagnosis-by-age</sub> = -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<sub>diagnosis</sub> = 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<sub>diagnosis</sub> = 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.