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2. ENIGMA-anxiety working group: Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Author

Bas-Hoogendam, J. M., Groenewold, N. A., Aghajani, M., Freitag, G. F., Harrewijn, A., Hilbert, K., Jahanshad, N., Thomopoulos, S. I., Thompson, P. M., Veltman, D. J., Winkler, A. M., Lueken, U., Pine, D. S., van der Wee, N. J. A., Stein, D. J., Agosta, F., Ahs, F., An, I., Alberton, B. A. V., Andreescu, C., Asami, T., Assaf, M., Avery, S. N., Nicholas, L., Balderston, Barber, J. P., Battaglia, M., Bayram, A., Beesdo-Baum, K., Benedetti, F., Berta, R., Bjorkstrand, J., Blackford, J. U., Blair, J. R., Karina, S., Blair, Boehme, S., Brambilla, P., Burkhouse, K., Cano, M., Canu, E., Cardinale, E. M., Cardoner, N., Clauss, J. A., Cividini, C., Critchley, H. D., Udo, Dannlowski, Deckert, J., Demiralp, T., Diefenbach, G. J., Domschke, K., Doruyter, A., Dresler, T., Erhardt, A., Fallgatter, A. J., Fananas, L., Brandee, Feola, Filippi, C. A., Filippi, M., Fonzo, G. A., Forbes, E. E., Fox, N. A., Fredrikson, M., Furmark, T., Ge, T., Gerber, A. J., Gosnell, S. N., Grabe, H. J., Grotegerd, D., Gur, R. E., Gur, R. C., Harmer, C. J., Harper, J., Heeren, A., Hettema, J., Hofmann, D., Hofmann, S. G., Jackowski, A. P., Andreas, Jansen, Kaczkurkin, A. N., Kingsley, E., Kircher, T., Kosti c, M., Kreifelts, B., Krug, A., Larsen, B., Lee, S. -H., Leehr, E. J., Leibenluft, E., Lochner, C., Maggioni, E., Makovac, E., Mancini, M., Manfro, G. G., Mansson, K. N. T., Meeten, F., Michalowski, J., Milrod, B. L., Muhlberger, A., Lilianne, R., Mujica-Parodi, Munjiza, A., Mwangi, B., Myers, M., Igor Nenadi, C., Neufang, S., Nielsen, J. A., Oh, H., Ottaviani, C., Pan, P. M., Pantazatos, S. P., Martin, P., Paulus, Perez-Edgar, K., Penate, W., Perino, M. T., Peterburs, J., Pfleiderer, B., Phan, K. L., Poletti, S., Porta-Casteras, D., Price, R. B., Pujol, J., Andrea, Reinecke, Rivero, F., Roelofs, K., Rosso, I., Saemann, P., Salas, R., Salum, G. A., Satterthwaite, T. D., Schneier, F., Schruers, K. R. J., Schulz, S. M., Schwarzmeier, H., Seeger, F. R., Smoller, J. W., Soares, J. C., Stark, R., Stein, M. B., Straube, B., Straube, T., Strawn, J. R., Suarez-Jimenez, B., Boris, Suchan, Sylvester, C. M., Talati, A., Tamburo, E., Tukel, R., van den Heuvel, O. A., Van der Auwera, S., van Nieuwenhuizen, H., van Tol, M. -J., van Velzen, L. S., Bort, C. V., Vermeiren, R. R. J. M., Visser, R. M., Volman, I., Wannemuller, A., Wendt, J., Werwath, K. E., Westenberg, P. M., Wiemer, J., Katharina, Wittfeld, M. -J., Wu, Yang, Y., Zilverstand, A., Zugman, A., Zwiebel, H. L., Bas-Hoogendam, J. M., Groenewold, N. A., Aghajani, M., Freitag, G. F., Harrewijn, A., Hilbert, K., Jahanshad, N., Thomopoulos, S. I., Thompson, P. M., Veltman, D. J., Winkler, A. M., Lueken, U., Pine, D. S., van der Wee, N. J. A., Stein, D. J., ENIGMA-anxiety working, Group, Filippi, M, and UCL - SSH/IPSY - Psychological Sciences Research Institute

Subjects
Córtex pré-frontal, Review Article, Anxiety, Prefrontal cortex, Specific phobia, 0302 clinical medicine, limbic system, magnetic resonance imaging, Multicenter Studies as Topic, genetics, Review Articles, prefrontal cortex, neuroimaging, Radiological and Ultrasound Technology, 05 social sciences, Social anxiety, amygdala, Amygdala, Anxiety Disorders, Transtornos de ansiedade, Neurology, multicentric network, Anatomy, medicine.symptom, Psychology, Neurovetenskaper, Clinical psychology, endocrine system, Generalized anxiety disorder, brain, Neuroimaging, Sistema límbico, 050105 experimental psychology, 03 medical and health sciences, Global mental health, Limbic system, Magnetic resonance imaging, Imatges per ressonància magnètica, medicine, Genetics, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Neuroimagem, Psykologi (exklusive tillämpad psykologi), Panic disorder, neurosciences, Imageamento por ressonância magnética, Tonsila do cerebelo, medicine.disease, anxiety disorders, Genética, Psychology (excluding Applied Psychology), Ansietat, Neurology (clinical), Working group, 030217 neurology & neurosurgery, Anxiety disorders
Abstract

Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA‐Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders., Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.

Published
2020

3. Cortical and subcortical brain structure in generalized anxiety disorder

Author

Paolo Brambilla, Tali M. Ball, Dan J. Stein, Courtney A. Filippi, Kathryn E. Werwath, Pedro Mario Pan, Heidi K. Schroeder, Hannah Zwiebel, Andrea Parolin Jackowski, Jared A. Nielsen, Savannah N. Gosnell, Hans J. Grabe, Christian Grillon, Paul M. Thompson, Gabrielle F. Freitag, Murray B. Stein, Karina S. Blair, Narcís Cardoner, Neda Jahanshad, Ana Munjiza Jovanovic, Cristina Ottaviani, Massimo Filippi, André Zugman, Katharina Wittfeld, Antonia N. Kaczkurkin, Camilla Cividini, Hugo D. Critchley, Nynke A. Groenewold, Elise M. Cardinale, Moji Aghajani, Bianca A.V. Alberton, Michael T. Perino, Anderson M. Winkler, Ellen Leibenluft, Sophia I. Thomopoulos, Mohammed R. Milad, Kevin Hilbert, Matteo Mancini, Randy L. Buckner, Henry Völzke, Robin Bülow, Carmen Andreescu, Milutin Kostić, Raquel E. Gur, Benson Mwangi, Daniel Porta-Casteràs, Michael J. Myers, Federica Agosta, Thomas Straube, Giovana Zunta-Soares, Gretchen J. Diefenbach, Martin P. Paulus, Erica Tamburo, Brenda E. Benson, Elena Makovac, Grace V. Ringlein, Andrea L. Gold, David Hofmann, Mon-Ju Wu, Jeffrey R. Strawn, Janna Marie Bas-Hoogendam, Dick J. Veltman, Eleonora Maggioni, Sandra Van der Auwera, Gregory A. Fonzo, Ramiro Salas, Giovanni Abrahão Salum, Daniel S. Pine, Gisele Gus Manfro, Bart Larsen, Monique Ernst, Nic J.A. van der Wee, Helena van Nieuwenhuizen, Mira Z. Hammoud, Ruben C. Gur, Katie L. Burkhouse, Chad M. Sylvester, Rachel Berta, Elisa Canu, Jair C. Soares, Theodore D. Satterthwaite, Qiongru Yu, Frances Meeten, Ulrike Lueken, Jordan W. Smoller, Michal Assaf, Lilianne R. Mujica-Parodi, K. Luan Phan, Jennifer Harper, Nicholas L. Balderston, James R. Blair, Anita Harrewijn, Rebecca B. Price, Katja Beesdo-Baum, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Anatomy and neurosciences, Amsterdam Neuroscience - Brain Imaging, Harrewijn, A., Cardinale, E. M., Groenewold, N. A., Bas-Hoogendam, J. M., Aghajani, M., Hilbert, K., Cardoner, N., Porta-Casteras, D., Gosnell, S., Salas, R., Jackowski, A. P., Pan, P. M., Salum, G. A., Blair, K. S., Blair, J. R., Hammoud, M. Z., Milad, M. R., Burkhouse, K. L., Phan, K. L., Schroeder, H. K., Strawn, J. R., Beesdo-Baum, K., Jahanshad, N., Thomopoulos, S. I., Buckner, R., Nielsen, J. A., Smoller, J. W., Soares, J. C., Mwangi, B., Wu, M. -J., Zunta-Soares, G. B., Assaf, M., Diefenbach, G. J., Brambilla, P., Maggioni, E., Hofmann, D., Straube, T., Andreescu, C., Berta, R., Tamburo, E., Price, R. B., Manfro, G. G., Agosta, F., Canu, E., Cividini, C., Filippi, M., Kostic, M., Munjiza Jovanovic, A., Alberton, B. A. V., Benson, B., Freitag, G. F., Filippi, C. A., Gold, A. L., Leibenluft, E., Ringlein, G. V., Werwath, K. E., Zwiebel, H., Zugman, A., Grabe, H. J., Van der Auwera, S., Wittfeld, K., Volzke, H., Bulow, R., Balderston, N. L., Ernst, M., Grillon, C., Mujica-Parodi, L. R., van Nieuwenhuizen, H., Critchley, H. D., Makovac, E., Mancini, M., Meeten, F., Ottaviani, C., Ball, T. M., Fonzo, G. A., Paulus, M. P., Stein, M. B., Gur, R. E., Gur, R. C., Kaczkurkin, A. N., Larsen, B., Satterthwaite, T. D., Harper, J., Myers, M., Perino, M. T., Sylvester, C. M., Yu, Q., Lueken, U., Veltman, D. J., Thompson, P. M., Stein, D. J., Van der Wee, N. J. A., Winkler, A. M., and Pine, D. S.

Subjects
Adult, Male, medicine.medical_specialty, endocrine system, Generalized anxiety disorder, Neurosciences. Biological psychiatry. Neuropsychiatry, Anxiety, Audiology, Article, Structural magnetic resonance imaging, Cellular and Molecular Neuroscience, Secondary analysis, medicine, Psychology, Humans, ddc:610, Cortical surface, generalized anxiety disorder, structural brain imaging, cortical thickness, Child, diagnostic imaging [Brain], Biological Psychiatry, Medication use, diagnostic imaging [Anxiety Disorders], medicine.diagnostic_test, business.industry, Brain, Small sample, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, Anxiety Disorders, Psychiatry and Mental health, multicentric network, Female, medicine.symptom, business, RC321-571, Neuroscience
Abstract

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.

Published
2021

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