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2. Brain-based classification of youth with anxiety disorders: transdiagnostic examinations within the ENIGMA-Anxiety database using machine learning

Author

Bruin, Willem B., Zhutovsky, Paul, van Wingen, Guido A., Bas-Hoogendam, Janna Marie, Groenewold, Nynke A., Hilbert, Kevin, Winkler, Anderson M., Zugman, Andre, Agosta, Federica, Åhs, Fredrik, Andreescu, Carmen, Antonacci, Chase, Asami, Takeshi, Assaf, Michal, Barber, Jacques P., Bauer, Jochen, Bavdekar, Shreya Y., Beesdo-Baum, Katja, Benedetti, Francesco, Bernstein, Rachel, Björkstrand, Johannes, Blair, Robert J., Blair, Karina S., Blanco-Hinojo, Laura, Böhnlein, Joscha, Brambilla, Paolo, Bressan, Rodrigo A., Breuer, Fabian, Cano, Marta, Canu, Elisa, Cardinale, Elise M., Cardoner, Narcís, Cividini, Camilla, Cremers, Henk, Dannlowski, Udo, Diefenbach, Gretchen J., Domschke, Katharina, Doruyter, Alexander G. G., Dresler, Thomas, Erhardt, Angelika, Filippi, Massimo, Fonzo, Gregory A., Freitag, Gabrielle F., Furmark, Tomas, Ge, Tian, Gerber, Andrew J., Gosnell, Savannah N., Grabe, Hans J., Grotegerd, Dominik, Gur, Ruben C., Gur, Raquel E., Hamm, Alfons O., Han, Laura K. M., Harper, Jennifer C., Harrewijn, Anita, Heeren, Alexandre, Hofmann, David, Jackowski, Andrea P., Jahanshad, Neda, Jett, Laura, Kaczkurkin, Antonia N., Khosravi, Parmis, Kingsley, Ellen N., Kircher, Tilo, Kostic, Milutin, Larsen, Bart, Lee, Sang-Hyuk, Leehr, Elisabeth J., Leibenluft, Ellen, Lochner, Christine, Lui, Su, Maggioni, Eleonora, Manfro, Gisele G., Månsson, Kristoffer N. T., Marino, Claire E., Meeten, Frances, Milrod, Barbara, Jovanovic, Ana Munjiza, Mwangi, Benson, Myers, Michael J., Neufang, Susanne, Nielsen, Jared A., Ohrmann, Patricia A., Ottaviani, Cristina, Paulus, Martin P., Perino, Michael T., Phan, K. Luan, Poletti, Sara, Porta-Casteràs, Daniel, Pujol, Jesus, Reinecke, Andrea, Ringlein, Grace V., Rjabtsenkov, Pavel, Roelofs, Karin, Salas, Ramiro, Salum, Giovanni A., Satterthwaite, Theodore D., Schrammen, Elisabeth, Sindermann, Lisa, Smoller, Jordan W., Soares, Jair C., Stark, Rudolf, Stein, Frederike, Straube, Thomas, Straube, Benjamin, Strawn, Jeffrey R., Suarez-Jimenez, Benjamin, Sylvester, Chad M., Talati, Ardesheer, Thomopoulos, Sophia I., Tükel, Raşit, van Nieuwenhuizen, Helena, Werwath, Kathryn, Wittfeld, Katharina, Wright, Barry, Wu, Mon-Ju, Yang, Yunbo, Zilverstand, Anna, Zwanzger, Peter, Blackford, Jennifer U., Avery, Suzanne N., Clauss, Jacqueline A., Lueken, Ulrike, Thompson, Paul M., Pine, Daniel S., Stein, Dan J., van der Wee, Nic J. A., Veltman, Dick J., and Aghajani, Moji

Published
2024
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3. Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group.

Author

Groenewold, Nynke, Bas-Hoogendam, Janna, Amod, Alyssa, Laansma, Max, Van Velzen, Laura, Aghajani, Moji, Hilbert, Kevin, Oh, Hyuntaek, Salas, Ramiro, Jackowski, Andrea, Pan, Pedro, Salum, Giovanni, Blair, James, Blair, Karina, Hirsch, Joy, Pantazatos, Spiro, Schneier, Franklin, Talati, Ardesheer, Roelofs, Karin, Volman, Inge, Blanco-Hinojo, Laura, Cardoner, Narcís, Pujol, Jesus, Beesdo-Baum, Katja, Ching, Christopher, Thomopoulos, Sophia, Jansen, Andreas, Kircher, Tilo, Krug, Axel, Nenadić, Igor, Stein, Frederike, Dannlowski, Udo, Grotegerd, Dominik, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Erb, Michael, Kreifelts, Benjamin, Gong, Qiyong, Lui, Su, Zhu, Fei, Mwangi, Benson, Soares, Jair, Wu, Mon-Ju, Bayram, Ali, Canli, Mesut, Tükel, Raşit, Westenberg, P, Heeren, Alexandre, Cremers, Henk, Hofmann, David, Straube, Thomas, Doruyter, Alexander, Lochner, Christine, Peterburs, Jutta, Van Tol, Marie-José, Gur, Raquel, Kaczkurkin, Antonia, Larsen, Bart, Satterthwaite, Theodore, Filippi, Courtney, Gold, Andrea, Harrewijn, Anita, Zugman, André, Bülow, Robin, Grabe, Hans, Völzke, Henry, Wittfeld, Katharina, Böhnlein, Joscha, Dohm, Katharina, Kugel, Harald, Schrammen, Elisabeth, Zwanzger, Peter, Leehr, Elisabeth, Sindermann, Lisa, Ball, Tali, Fonzo, Gregory, Paulus, Martin, Stein, Murray, Klumpp, Heide, Phan, K, Furmark, Tomas, Månsson, Kristoffer, Manzouri, Amirhossein, Avery, Suzanne, Blackford, Jennifer, Clauss, Jacqueline, Feola, Brandee, Harper, Jennifer, Sylvester, Chad, Lueken, Ulrike, Veltman, Dick, Winkler, Anderson, Jahanshad, Neda, Pine, Daniel, Thompson, Paul, Stein, Dan, Van der Wee, Nic, and Simmons, Alan

Subjects
Adult, Adolescent, Humans, Phobia, Social, Magnetic Resonance Imaging, Brain, Anxiety, Neuroimaging
Abstract

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE

Published
2023

4. Understanding psychotic-like experiences in children in the context of dimensions of psychological problems

Author

Hee Jung Jeong, Benjamin B. Lahey, Gabrielle E. Reimann, E. Leighton Durham, Camille Archer, Tyler M. Moore, Krisha Shah, and Antonia N. Kaczkurkin

Subjects
psychotic-like experience, general psychopathology, ADHD, conduct problems, children, Psychiatry, RC435-571, Pediatrics, RJ1-570
Abstract

IntroductionAlthough psychotic behaviors can be difficult to assess in children, early identification of children at high risk for the emergence of psychotic symptoms may facilitate the prevention of related disorders. Psychotic-like experiences (PLEs), or subthreshold thought and perceptual disturbances, could be early manifestations of psychosis that may predict a future diagnosis of a psychosis-related disorder or nonspecific correlates of a wide range of psychological problems. Additional research is needed regarding how PLEs map onto dimensions of psychopathology in children.MethodsIn the present study, we examined the association between PLEs and general and specific dimensions of psychological problems in a sample of 10,692 children from the Adolescent Brain Cognitive Development Study (ABCD Study).ResultsThe results of this study showed that self-reported PLEs were associated with a general psychopathology factor and an ADHD factor, which were defined in hierarchical models of parent-rated psychological problems.DiscussionThese findings suggest that PLEs are broadly associated with a wide range of psychological problems through the general psychopathology factor even before psychotic disorders typically manifest. This study supports the need for longitudinal analyses of future waves of the ABCD Study to determine if PLEs can detect children at high risk for serious psychological problems in adulthood.

Published
2024
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6. Early life stress and functional network topology in children

Author

Hee Jung Jeong, Gabrielle E. Reimann, E. Leighton Durham, Camille Archer, Andrew J. Stier, Tyler M. Moore, Julia R. Pines, Marc G. Berman, and Antonia N. Kaczkurkin

Subjects
Early life stress, Youth, Function, Networks, Topology, Neurophysiology and neuropsychology, QP351-495
Abstract

Brain networks are continuously modified throughout development, yet this plasticity can also make functional networks vulnerable to early life stress. Little is currently known about the effect of early life stress on the functional organization of the brain. The current study investigated the association between environmental stressors and network topology using data from the Adolescent Brain Cognitive DevelopmentSM (ABCD®) Study. Hierarchical modeling identified a general factor of environmental stress, representing the common variance across multiple stressors, as well as four subfactors including familial dynamics, interpersonal support, neighborhood SES deprivation, and urbanicity. Functional network topology metrics were obtained using graph theory at rest and during tasks of reward processing, inhibition, and affective working memory. The general factor of environmental stress was associated with less specialization of networks, represented by lower modularity at rest. Local metrics indicated that general environmental stress was also associated with less efficiency in the subcortical-cerebellar and visual networks while showing greater efficiency in the default mode network at rest. Subfactors of environmental stress were associated with differences in specialization and efficiency in select networks. The current study illustrates that a wide range of stressors in a child’s environment are associated with differences in brain network topology.

Published
2024
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8. Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium

Author

Dwyer, Dominic B., Chand, Ganesh B., Pigoni, Alessandro, Khuntia, Adyasha, Wen, Junhao, Antoniades, Mathilde, Hwang, Gyujoon, Erus, Guray, Doshi, Jimit, Srinivasan, Dhivya, Varol, Erdem, Kahn, Rene S., Schnack, Hugo G., Meisenzahl, Eva, Wood, Stephen J., Zhuo, Chuanjun, Sotiras, Aristeidis, Shinohara, Russell T., Shou, Haochang, Fan, Yong, Schaulfelberger, Maristela, Rosa, Pedro, Lalousis, Paris A., Upthegrove, Rachel, Kaczkurkin, Antonia N., Moore, Tyler M., Nelson, Barnaby, Gur, Raquel E., Gur, Ruben C., Ritchie, Marylyn D., Satterthwaite, Theodore D., Murray, Robin M., Di Forti, Marta, Ciufolini, Simone, Zanetti, Marcus V., Wolf, Daniel H., Pantelis, Christos, Crespo-Facorro, Benedicto, Busatto, Geraldo F., Davatzikos, Christos, Koutsouleris, Nikolaos, and Dazzan, Paola

Published
2023
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9. Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group

Author

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

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Clinical Sciences, Psychology, Biomedical Imaging, Neurosciences, Brain Disorders, Women's Health, Behavioral and Social Science, 4.2 Evaluation of markers and technologies, Mental health, Adult, Anxiety, Anxiety Disorders, Brain, Child, Female, Humans, Magnetic Resonance Imaging, Male, Public Health and Health Services, Clinical sciences, Biological psychology
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

14. Multivariate analytical approaches for investigating brain-behavior relationships

Author

E. Leighton Durham, Karam Ghanem, Andrew J. Stier, Carlos Cardenas-Iniguez, Gabrielle E. Reimann, Hee Jung Jeong, Randolph M. Dupont, Xiaoyu Dong, Tyler M. Moore, Marc G. Berman, Benjamin B. Lahey, Danilo Bzdok, and Antonia N. Kaczkurkin

Subjects
canonical correlation analysis, partial least squares, gray matter volume, psychopathology, brain development, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

BackgroundMany studies of brain-behavior relationships rely on univariate approaches where each variable of interest is tested independently, which does not allow for the simultaneous investigation of multiple correlated variables. Alternatively, multivariate approaches allow for examining relationships between psychopathology and neural substrates simultaneously. There are multiple multivariate methods to choose from that each have assumptions which can affect the results; however, many studies employ one method without a clear justification for its selection. Additionally, there are few studies illustrating how differences between methods manifest in examining brain-behavior relationships. The purpose of this study was to exemplify how the choice of multivariate approach can change brain-behavior interpretations.MethodWe used data from 9,027 9- to 10-year-old children from the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®) to examine brain-behavior relationships with three commonly used multivariate approaches: canonical correlation analysis (CCA), partial least squares correlation (PLSC), and partial least squares regression (PLSR). We examined the associations between psychopathology dimensions including general psychopathology, attention-deficit/hyperactivity symptoms, conduct problems, and internalizing symptoms with regional brain volumes.ResultsThe results of CCA, PLSC, and PLSR showed both consistencies and differences in the relationship between psychopathology symptoms and brain structure. The leading significant component yielded by each method demonstrated similar patterns of associations between regional brain volumes and psychopathology symptoms. However, the additional significant components yielded by each method demonstrated differential brain-behavior patterns that were not consistent across methods.ConclusionHere we show that CCA, PLSC, and PLSR yield slightly different interpretations regarding the relationship between child psychopathology and brain volume. In demonstrating the divergence between these approaches, we exemplify the importance of carefully considering the method’s underlying assumptions when choosing a multivariate approach to delineate brain-behavior relationships.

Published
2023
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16. Direct and Indirect Associations of Widespread Individual Differences in Brain White Matter Microstructure With Executive Functioning and General and Specific Dimensions of Psychopathology in Children

Author

Cardenas-Iniguez, Carlos, Moore, Tyler M., Kaczkurkin, Antonia N., Meyer, Francisco A.C., Satterthwaite, Theodore D., Fair, Damien A., White, Tonya, Blok, Elisabet, Applegate, Brooks, Thompson, Lauren M., Rosenberg, Monica D., Hedeker, Donald, Berman, Marc G., and Lahey, Benjamin B.

Published
2022
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17. 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

Author

Hilbert, Kevin, primary, Boeken, Ole Jonas, additional, Langhammer, Till, additional, Groenewold, Nynke A., additional, Bas-Hoogendam, Janna Marie, additional, Aghajani, Moji, additional, Zugman, André, additional, Åhs, Fredrik, additional, Arolt, Volker, additional, Beesdo-Baum, Katja, additional, Björkstrand, Johannes, additional, Blackford, Jennifer U., additional, Blanco-Hinojo, Laura, additional, Böhnlein, Joscha, additional, Bülow, Robin, additional, Cano, Marta, additional, Cardoner, Narcis, additional, Caseras, Xavier, additional, Dannlowski, Udo, additional, Domschke, Katharina, additional, Fehm, Lydia, additional, Feola, Brandee, additional, Fredrikson, Mats, additional, Goossens, Liesbet, additional, Grabe, Hans J., additional, Grotegerd, Dominik, additional, Gur, Raquel E., additional, Hamm, Alfons O., additional, Harrewijn, Anita, additional, Heinig, Ingmar, additional, Herrmann, Martin J., additional, Hofmann, David, additional, Jackowski, Andrea P., additional, Jansen, Andreas, additional, Kaczkurkin, Antonia N., additional, Kindt, Merel, additional, Kingsley, Ellen N., additional, Kircher, Tilo, additional, Klahn, Anna L., additional, Koelkebeck, Katja, additional, Krug, Axel, additional, Kugel, Harald, additional, Larsen, Bart, additional, Leehr, Elisabeth J., additional, Leonhardt, Lieselotte, additional, Lotze, Martin, additional, Margraf, Jürgen, additional, Michałowski, Jarosław, additional, Muehlhan, Markus, additional, Nenadić, Igor, additional, Pan, Pedro M., additional, Pauli, Paul, additional, Peñate, Wenceslao, additional, Pittig, Andre, additional, Plag, Jens, additional, Pujol, Jesus, additional, Richter, Jan, additional, Rivero, Francisco L., additional, Salum, Giovanni A., additional, Satterthwaite, Theodore D., additional, Schäfer, Axel, additional, Schäfer, Judith, additional, Schienle, Anne, additional, Schneider, Silvia, additional, Schrammen, Elisabeth, additional, Schruers, Koen, additional, Schulz, Stefan M., additional, Seidl, Esther, additional, Stark, Rudolf M., additional, Stein, Frederike, additional, Straube, Benjamin, additional, Straube, Thomas, additional, Ströhle, Andreas, additional, Suchan, Boris, additional, Thomopoulos, Sophia I., additional, Ventura-Bort, Carlos, additional, Visser, Renee, additional, Völzke, Henry, additional, Wabnegger, Albert, additional, Wannemüller, André, additional, Wendt, Julia, additional, Wiemer, Julian, additional, Wittchen, Hans-Ulrich, additional, Wittfeld, Katharina, additional, Wright, Barry, additional, Yang, Yunbo, additional, Zilverstand, Anna, additional, Zwanzger, Peter, additional, Veltman, Dick J., additional, Winkler, Anderson M., additional, Pine, Daniel S., additional, Jahanshad, Neda, additional, Thompson, Paul M., additional, Stein, Dan J., additional, Van der Wee, Nic J.A., additional, and Lueken, Ulrike, additional

Published
2024
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18. 455. AI-Derived Neuroanatomical Subtypes of Schizophrenia and Their Expression During Disease Onset and in Unaffected Siblings

Author

Antoniades, Mathilde, primary, Yang, Zhijian, additional, Chand, Ganesh, additional, Schnack, Hugo, additional, Shinohara, Russell T., additional, Kaczkurkin, Antonia N., additional, Moore, Tyler M., additional, Gur, Raquel E., additional, Satterthwaite, Theodore D., additional, Di Forti, Marta, additional, Ciufolini, Simone, additional, Zanetti, Marcus V., additional, Crespo-Facorro, Benedicto, additional, Busatto, Geraldo F., additional, Wolf, Daniel H., additional, Dazzan, Paola, additional, Koutsouleris, Nikolaos, additional, and Davatzikos, Christos, additional

Published
2024
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19. Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group

Author

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

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

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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23. The association between latent trauma and brain structure in children

Author

Hee Jung Jeong, E. Leighton Durham, Tyler M. Moore, Randolph M. Dupont, Malerie McDowell, Carlos Cardenas-Iniguez, Emily T. Micciche, Marc G. Berman, Benjamin B. Lahey, and Antonia N. Kaczkurkin

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract The developing brain is marked by high plasticity, which can lead to vulnerability to early life stressors. Previous studies indicate that childhood maltreatment is associated with structural aberrations across a number of brain regions. However, prior work is limited by small sample sizes, heterogeneous age groups, the examination of one structure in isolation, the confounding of different types of early life stressors, and not accounting for socioeconomic status. These limitations may contribute to high variability across studies. The present study aimed to investigate how trauma is specifically associated with cortical thickness and gray matter volume (GMV) differences by leveraging a large sample of children (N = 9270) from the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). A latent measure of trauma exposure was derived from DSM-5 traumatic events, and we related this measure of trauma to the brain using structural equation modeling. Trauma exposure was associated with thinner cortices in the bilateral superior frontal gyri and right caudal middle frontal gyrus (p fdr -values

Published
2021
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25. Mapping potential pathways from polygenic liability through brain structure to psychological problems across the transition to adolescence.

Author

Lahey, Benjamin B., Durham, E. Leighton, Brislin, Sarah J., Barr, Peter B., Dick, Danielle M., Moore, Tyler M., Pierce, Brandon L., Tong, Lin, Reimann, Gabrielle E., Jeong, Hee Jung, Dupont, Randolph M., and Kaczkurkin, Antonia N.

Subjects
ADOLESCENT development, RISK assessment, ATTENTION-deficit hyperactivity disorder, RESEARCH funding, RISK-taking behavior, BRAIN, MENTAL illness, CELLULAR signal transduction, MAGNETIC resonance imaging, UNSAFE sex, QUALITY control, STRUCTURAL equation modeling, DESCRIPTIVE statistics, GENETIC risk score, TEENAGERS' conduct of life, BEHAVIOR disorders in children, LONGITUDINAL method, GRAY matter (Nerve tissue), CHILD Behavior Checklist, NEURORADIOLOGY, QUALITY assurance, FACTOR analysis, COMPARATIVE studies, DATA analysis software, TRANSITION to adulthood, GENETICS, GENOTYPES, ADOLESCENCE
Abstract

Background: We used a polygenic score for externalizing behavior (extPGS) and structural MRI to examine potential pathways from genetic liability to conduct problems via the brain across the adolescent transition. Methods: Three annual assessments of child conduct problems, attention‐deficit/hyperactivity problems, and internalizing problems were conducted across across 9–13 years of age among 4,475 children of European ancestry in the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). Results: The extPGS predicted conduct problems in each wave (R2 = 2.0%–2.9%). Bifactor models revealed that the extPRS predicted variance specific to conduct problems (R2 = 1.7%–2.1%), but also variance that conduct problems shared with other measured problems (R2 =.8%–1.4%). Longitudinally, extPGS predicted levels of specific conduct problems (R2 = 2.0%), but not their slope of change across age. The extPGS was associated with total gray matter volume (TGMV; R2 =.4%) and lower TGMV predicted both specific conduct problems (R2 = 1.7%–2.1%) and the variance common to all problems in each wave (R2 = 1.6%–3.1%). A modest proportion of the polygenic liability specific to conduct problems in each wave was statistically mediated by TGMV. Conclusions: Across the adolescent transition, the extPGS predicted both variance specific to conduct problems and variance shared by all measured problems. The extPGS also was associated with TGMV, which robustly predicted conduct problems. Statistical mediation analyses suggested the hypothesis that polygenic variation influences individual differences in brain development that are related to the likelihood of conduct problems during the adolescent transition, justifying new research to test this causal hypothesis. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Neurostructural Heterogeneity in Youths With Internalizing Symptoms

Author

Kaczkurkin, Antonia N., Sotiras, Aristeidis, Baller, Erica B., Barzilay, Ran, Calkins, Monica E., Chand, Ganesh B., Cui, Zaixu, Erus, Guray, Fan, Yong, Gur, Raquel E., Gur, Ruben C., Moore, Tyler M., Roalf, David R., Rosen, Adon F.G., Ruparel, Kosha, Shinohara, Russell T., Varol, Erdem, Wolf, Daniel H., Davatzikos, Christos, and Satterthwaite, Theodore D.

Published
2020
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31. Neurocognitive and functional heterogeneity in depressed youth

Author

Baller, Erica B., Kaczkurkin, Antonia N., Sotiras, Aristeidis, Adebimpe, Azeez, Bassett, Danielle S., Calkins, Monica E., Chand, Ganesh B., Cui, Zaixu, Gur, Raquel E., Gur, Ruben C., Linn, Kristin A., Moore, Tyler M., Roalf, David R., Varol, Erdem, Wolf, Daniel H., Xia, Cedric H., Davatzikos, Christos, and Satterthwaite, Theodore D.

Published
2021
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32. Structural brain networks in remitted psychotic depression

Author

Neufeld, Nicholas H., Kaczkurkin, Antonia N., Sotiras, Aristeidis, Mulsant, Benoit H., Dickie, Erin W., Flint, Alastair J., Meyers, Barnett S., Alexopoulos, George S., Rothschild, Anthony J., Whyte, Ellen M., Mah, Linda, Nierenberg, Jay, Hoptman, Matthew J., Davatzikos, Christos, Satterthwaite, Theodore D., and Voineskos, Aristotle N.

Published
2020
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34. Accelerated cortical thinning within structural brain networks is associated with irritability in youth

Author

Jirsaraie, Robert J., Kaczkurkin, Antonia N., Rush, Sage, Piiwia, Kayla, Adebimpe, Azeez, Bassett, Danielle S., Bourque, Josiane, Calkins, Monica E., Cieslak, Matthew, Ciric, Rastko, Cook, Philip A., Davila, Diego, Elliott, Mark A., Leibenluft, Ellen, Murtha, Kristin, Roalf, David R., Rosen, Adon F. G., Ruparel, Kosha, Shinohara, Russell T., Sotiras, Aristeidis, Wolf, Daniel H., Davatzikos, Christos, and Satterthwaite, Theodore D.

Published
2019
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36. Linked dimensions of psychopathology and connectivity in functional brain networks

Author

Cedric Huchuan Xia, Zongming Ma, Rastko Ciric, Shi Gu, Richard F. Betzel, Antonia N. Kaczkurkin, Monica E. Calkins, Philip A. Cook, Angel García de la Garza, Simon N. Vandekar, Zaixu Cui, Tyler M. Moore, David R. Roalf, Kosha Ruparel, Daniel H. Wolf, Christos Davatzikos, Ruben C. Gur, Raquel E. Gur, Russell T. Shinohara, Danielle S. Bassett, and Theodore D. Satterthwaite

Subjects
Science
Abstract

Co-morbidity and symptom overlap make it difficult to associate psychiatric disorders with unique neural signatures. Here, the authors use a data-driven approach to show that the symptom dimensions of mood, psychosis, fear and externalizing behavior exhibit unique patterns of functional dysconnectivity.

Published
2018
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37. Multivariate analytical approaches for investigating brain-behavior relationships

Author

Durham, E. Leighton, primary, Ghanem, Karam, additional, Stier, Andrew J., additional, Cardenas-Iniguez, Carlos, additional, Reimann, Gabrielle E., additional, Jeong, Hee Jung, additional, Dupont, Randolph M., additional, Dong, Xiaoyu, additional, Moore, Tyler M., additional, Berman, Marc G., additional, Lahey, Benjamin B., additional, Bzdok, Danilo, additional, and Kaczkurkin, Antonia N., additional

Published
2023
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40. Schizophrenia Imaging Signatures and Their Associations With Cognition, Psychopathology, and Genetics in the General Population

Author

Ganesh B. Chand, Pankhuri Singhal, Dominic B. Dwyer, Junhao Wen, Guray Erus, Jimit Doshi, Dhivya Srinivasan, Elizabeth Mamourian, Erdem Varol, Aristeidis Sotiras, Gyujoon Hwang, Paola Dazzan, Rene S. Kahn, Hugo G. Schnack, Marcus V. Zanetti, Eva Meisenzahl, Geraldo F. Busatto, Benedicto Crespo-Facorro, Christos Pantelis, Stephen J. Wood, Chuanjun Zhuo, Russell T. Shinohara, Haochang Shou, Yong Fan, Nikolaos Koutsouleris, Antonia N. Kaczkurkin, Tyler M. Moore, Anurag Verma, Monica E. Calkins, Raquel E. Gur, Ruben C. Gur, Marylyn D. Ritchie, Theodore D. Satterthwaite, Daniel H. Wolf, and Christos Davatzikos

Subjects
Polygenic Risk Scores, Neuroimaging, Schizophrenia Spectrum and Other Psychotic Disorders, Article, Machine Learning, Neuroanatomy, Psychiatry and Mental health, Cognition, Cross-Sectional Studies, Psychotic Disorders, Schizophrenia, Humans, Gray Matter, Genetics/Genomics
Abstract

OBJECTIVE: The prevalence and significance of schizophrenia-related phenotypes at the population level is debated in the literature. Here, the authors assessed whether two recently reported neuroanatomical signatures of schizophrenia—signature 1, with widespread reduction of gray matter volume, and signature 2, with increased striatal volume—could be replicated in an independent schizophrenia sample, and investigated whether expression of these signatures can be detected at the population level and how they relate to cognition, psychosis spectrum symptoms, and schizophrenia genetic risk. METHODS: This cross-sectional study used an independent schizophrenia-control sample (N=347; ages 16–57 years) for replication of imaging signatures, and then examined two independent population-level data sets: typically developing youths and youths with psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort (N=359; ages 16–23 years) and adults in the UK Biobank study (N=836; ages 44–50 years). The authors quantified signature expression using support-vector machine learning and compared cognition, psychopathology, and polygenic risk between signatures. RESULTS: Two neuroanatomical signatures of schizophrenia were replicated. Signature 1 but not signature 2 was significantly more common in youths with psychosis spectrum symptoms than in typically developing youths, whereas signature 2 frequency was similar in the two groups. In both youths and adults, signature 1 was associated with worse cognitive performance than signature 2. Compared with adults with neither signature, adults expressing signature 1 had elevated schizophrenia polygenic risk scores, but this was not seen for signature 2. CONCLUSIONS: The authors successfully replicated two neuroanatomical signatures of schizophrenia and describe their prevalence in population-based samples of youths and adults. They further demonstrated distinct relationships of these signatures with psychosis symptoms, cognition, and genetic risk, potentially reflecting underlying neurobiological vulnerability.

Published
2022
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41. Emotional numbing in PTSD is associated with lower amygdala reactivity to pain

Author

Nachshon Korem, Or Duek, Ziv Ben-Zion, Antonia N. Kaczkurkin, Shmuel Lissek, Temidayo Orederu, Daniela Schiller, Ilan Harpaz-Rotem, and Ifat Levy

Subjects
Stress Disorders, Post-Traumatic, Pharmacology, Psychiatry and Mental health, Emotions, Humans, Pain, Amygdala, Magnetic Resonance Imaging, Veterans
Abstract

Posttraumatic stress disorder (PTSD) is associated with altered pain perception, namely increased pain threshold and higher pain response. While pain consists of physiological and affective components, affective components are often overlooked. Similar patterns of increased threshold-high response in PTSD were shown in response to emotional stimuli, i.e., emotional numbing. As both emotional numbing and pain processing are modulated by the amygdala, we aimed to examine whether individuals diagnosed with PTSD show lower amygdala activation to pain compared with combat controls, and whether the amygdala responses to pain correlates with emotional numbing. To do so, two independent samples of veterans (original study: 44 total (20 PTSD); conceptual replication study: 40 total (20 PTSD)) underwent threat conditioning, where a conditioned stimulus (CS+; visual stimulus) was paired with an unconditioned stimulus (US; electric-shock). We contrasted the amygdala activity to the CS + US pairing with the CS+ presented alone and correlated it with emotional numbing severity. In both samples, the PTSD group showed a robust reduction in amygdala reactivity to shock compared to the Combat Controls group. Furthermore, amygdala activation was negatively correlated with emotional numbing severity. These patterns were unique to the amygdala, and did not appear in comparison to a control region, the insula, a pivotal region for the processing of pain. To conclude, amygdala response to pain is lower in individuals with PTSD, and is associated with emotional numbing symptoms. Lower amygdala reactivity to mild pain may contribute to the "all-or-none" reaction to stressful situations often observed in PTSD.

Published
2022
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42. Associations of polygenic risk for attention-deficit/hyperactivity disorder with general and specific dimensions of childhood psychological problems and facets of impulsivity

Author

Benjamin B, Lahey, Lin, Tong, Brandon, Pierce, Donald, Hedeker, Marc G, Berman, Carlos, Cardenas-Iniguez, Tyler M, Moore, Brooks, Applegate, Henning, Tiemeier, and Antonia N, Kaczkurkin

Subjects
Executive Function, Multifactorial Inheritance, Psychiatry and Mental health, Adolescent, Attention Deficit Disorder with Hyperactivity, Impulsive Behavior, Humans, Prospective Studies, Child, Biological Psychiatry
Abstract

A polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) has been found to be associated with ADHD in multiple studies, but also with many other dimensions of problems. Little is known, however, about the processes underlying these transdiagnostic associations. Using data from the baseline and 1-year follow-up assessments of 9- to 10-year-old children in the Adolescent Brain Cognitive Development™ (ABCD©) Study, associations were assessed between an ADHD PRS and both general and specific factors of psychological problems defined in bifactor modeling. Additionally, prospective mediated paths were tested from the ADHD PRS to dimensions of problems in the follow-up assessment through baseline measures of executive functioning (EF) and two facets of impulsivity: lower perseverance and greater impulsiveness in the presence of surgent positive emotions. Previous findings of modest but significant direct associations of the ADHD PRS with the general factor of psychological problems were replicated in both assessments in 4,483 children of European ancestry. In addition, significant statistical mediation was found from the ADHD PRS to the general factor, specific ADHD, and conduct problems in the follow-up assessment through each of the two facets of impulsivity. In contrast, EF did not statistically mediate associations between the ADHD PRS and psychological problems. These results suggest that polygenic risk transdiagnostically influences both psychological problems and facets of impulsivity, perhaps partly through indirect pathways via facets of impulsivity.

Published
2022
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43. 138. Functional Network Topology and Environmental Stressor

Author

Jeong, Hee Jung, primary, Reimann, Gabrielle, additional, Durham, E. Leighton, additional, Stier, Andrew J., additional, Moore, Tyler, additional, Dupont, Randolph M., additional, Pines, Julia R., additional, Berman, Marc G., additional, and Kaczkurkin, Antonia, additional

Published
2023
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44. Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group.

Author

Groenewold, NA, Bas-Hoogendam, JM, Amod, AR, Laansma, MA, Van Velzen, LS, Aghajani, M, Hilbert, K, Oh, H, Salas, R, Jackowski, AP, Pan, PM, Salum, GA, Blair, JR, Blair, KS, Hirsch, J, Pantazatos, SP, Schneier, FR, Talati, A, Roelofs, K, Volman, I, Blanco-Hinojo, L, Cardoner, N, Pujol, J, Beesdo-Baum, K, Ching, CRK, Thomopoulos, SI, Jansen, A, Kircher, T, Krug, A, Nenadić, I, Stein, F, Dannlowski, U, Grotegerd, D, Lemke, H, Meinert, S, Winter, A, Erb, M, Kreifelts, B, Gong, Q, Lui, S, Zhu, F, Mwangi, B, Soares, JC, Wu, M-J, Bayram, A, Canli, M, Tükel, R, Westenberg, PM, Heeren, A, Cremers, HR, Hofmann, D, Straube, T, Doruyter, AGG, Lochner, C, Peterburs, J, Van Tol, M-J, Gur, RE, Kaczkurkin, AN, Larsen, B, Satterthwaite, TD, Filippi, CA, Gold, AL, Harrewijn, A, Zugman, A, Bülow, R, Grabe, HJ, Völzke, H, Wittfeld, K, Böhnlein, J, Dohm, K, Kugel, H, Schrammen, E, Zwanzger, P, Leehr, EJ, Sindermann, L, Ball, TM, Fonzo, GA, Paulus, MP, Simmons, A, Stein, MB, Klumpp, H, Phan, KL, Furmark, T, Månsson, KNT, Manzouri, A, Avery, SN, Blackford, JU, Clauss, JA, Feola, B, Harper, JC, Sylvester, CM, Lueken, U, Veltman, DJ, Winkler, AM, Jahanshad, N, Pine, DS, Thompson, PM, Stein, DJ, Van der Wee, NJA, Groenewold, NA, Bas-Hoogendam, JM, Amod, AR, Laansma, MA, Van Velzen, LS, Aghajani, M, Hilbert, K, Oh, H, Salas, R, Jackowski, AP, Pan, PM, Salum, GA, Blair, JR, Blair, KS, Hirsch, J, Pantazatos, SP, Schneier, FR, Talati, A, Roelofs, K, Volman, I, Blanco-Hinojo, L, Cardoner, N, Pujol, J, Beesdo-Baum, K, Ching, CRK, Thomopoulos, SI, Jansen, A, Kircher, T, Krug, A, Nenadić, I, Stein, F, Dannlowski, U, Grotegerd, D, Lemke, H, Meinert, S, Winter, A, Erb, M, Kreifelts, B, Gong, Q, Lui, S, Zhu, F, Mwangi, B, Soares, JC, Wu, M-J, Bayram, A, Canli, M, Tükel, R, Westenberg, PM, Heeren, A, Cremers, HR, Hofmann, D, Straube, T, Doruyter, AGG, Lochner, C, Peterburs, J, Van Tol, M-J, Gur, RE, Kaczkurkin, AN, Larsen, B, Satterthwaite, TD, Filippi, CA, Gold, AL, Harrewijn, A, Zugman, A, Bülow, R, Grabe, HJ, Völzke, H, Wittfeld, K, Böhnlein, J, Dohm, K, Kugel, H, Schrammen, E, Zwanzger, P, Leehr, EJ, Sindermann, L, Ball, TM, Fonzo, GA, Paulus, MP, Simmons, A, Stein, MB, Klumpp, H, Phan, KL, Furmark, T, Månsson, KNT, Manzouri, A, Avery, SN, Blackford, JU, Clauss, JA, Feola, B, Harper, JC, Sylvester, CM, Lueken, U, Veltman, DJ, Winkler, AM, Jahanshad, N, Pine, DS, Thompson, PM, Stein, DJ, and Van der Wee, NJA

Abstract

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE < 0.001; right: d = -0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.

Published
2023

45. Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group

Author

UCL - SSH/IPSY - Psychological Sciences Research Institute, UCL - SSS/IONS/NEUR - Clinical Neuroscience, Groenewold, Nynke A., Bas-Hoogendam, Janna Marie, Amod, Alyssa R., Laansma, Max A., Van Velzen, Laura S., Aghajani, Moji, Hilbert, Kevin, Oh, Hyuntaek, Salas, Ramiro, Jackowski, Andrea P., Pan, Pedro M., Salum, Giovanni A., Blair, James R., Blair, Karina S., Hirsch, Joy, Pantazatos, Spiro P., Schneier, Franklin R., Talati, Ardesheer, Roelofs, Karin, Volman, Inge, Blanco-Hinojo, Laura, Cardoner, Narcís, Pujol, Jesus, Beesdo-Baum, Katja, Ching, Christopher R. K., Thomopoulos, Sophia I., Jansen, Andreas, Kircher, Tilo, Krug, Axel, Nenadić, Igor, Stein, Frederike, Dannlowski, Udo, Grotegerd, Dominik, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Erb, Michael, Kreifelts, Benjamin, Gong, Qiyong, Lui, Su, Zhu, Fei, Mwangi, Benson, Soares, Jair C., Wu, Mon-Ju, Bayram, Ali, Canli, Mesut, Tükel, Raşit, Westenberg, P. Michiel, Heeren, Alexandre, Cremers, Henk R., Hofmann, David, Straube, Thomas, Doruyter, Alexander G. G., Lochner, Christine, Peterburs, Jutta, Van Tol, Marie-José, Gur, Raquel E., Kaczkurkin, Antonia N., Larsen, Bart, Satterthwaite, Theodore D., Filippi, Courtney A., Gold, Andrea L., Harrewijn, Anita, Zugman, André, Bülow, Robin, Grabe, Hans J., Völzke, Henry, Wittfeld, Katharina, Böhnlein, Joscha, Dohm, Katharina, Kugel, Harald, Schrammen, Elisabeth, Zwanzger, Peter, Leehr, Elisabeth J., Sindermann, Lisa, Ball, Tali M., Fonzo, Gregory A., Paulus, Martin P., Simmons, Alan, Stein, Murray B., Klumpp, Heide, Phan, K. Luan, Furmark, Tomas, Månsson, Kristoffer N. T., Manzouri, Amirhossein, Avery, Suzanne N., Blackford, Jennifer Urbano, Clauss, Jacqueline A., Feola, Brandee, Harper, Jennifer C., Sylvester, Chad M., Lueken, Ulrike, Veltman, Dick J., Winkler, Anderson M., Jahanshad, Neda, Pine, Daniel S., Thompson, Paul M., Stein, Dan J., Van der Wee, Nic J. A., UCL - SSH/IPSY - Psychological Sciences Research Institute, UCL - SSS/IONS/NEUR - Clinical Neuroscience, Groenewold, Nynke A., Bas-Hoogendam, Janna Marie, Amod, Alyssa R., Laansma, Max A., Van Velzen, Laura S., Aghajani, Moji, Hilbert, Kevin, Oh, Hyuntaek, Salas, Ramiro, Jackowski, Andrea P., Pan, Pedro M., Salum, Giovanni A., Blair, James R., Blair, Karina S., Hirsch, Joy, Pantazatos, Spiro P., Schneier, Franklin R., Talati, Ardesheer, Roelofs, Karin, Volman, Inge, Blanco-Hinojo, Laura, Cardoner, Narcís, Pujol, Jesus, Beesdo-Baum, Katja, Ching, Christopher R. K., Thomopoulos, Sophia I., Jansen, Andreas, Kircher, Tilo, Krug, Axel, Nenadić, Igor, Stein, Frederike, Dannlowski, Udo, Grotegerd, Dominik, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Erb, Michael, Kreifelts, Benjamin, Gong, Qiyong, Lui, Su, Zhu, Fei, Mwangi, Benson, Soares, Jair C., Wu, Mon-Ju, Bayram, Ali, Canli, Mesut, Tükel, Raşit, Westenberg, P. Michiel, Heeren, Alexandre, Cremers, Henk R., Hofmann, David, Straube, Thomas, Doruyter, Alexander G. G., Lochner, Christine, Peterburs, Jutta, Van Tol, Marie-José, Gur, Raquel E., Kaczkurkin, Antonia N., Larsen, Bart, Satterthwaite, Theodore D., Filippi, Courtney A., Gold, Andrea L., Harrewijn, Anita, Zugman, André, Bülow, Robin, Grabe, Hans J., Völzke, Henry, Wittfeld, Katharina, Böhnlein, Joscha, Dohm, Katharina, Kugel, Harald, Schrammen, Elisabeth, Zwanzger, Peter, Leehr, Elisabeth J., Sindermann, Lisa, Ball, Tali M., Fonzo, Gregory A., Paulus, Martin P., Simmons, Alan, Stein, Murray B., Klumpp, Heide, Phan, K. Luan, Furmark, Tomas, Månsson, Kristoffer N. T., Manzouri, Amirhossein, Avery, Suzanne N., Blackford, Jennifer Urbano, Clauss, Jacqueline A., Feola, Brandee, Harper, Jennifer C., Sylvester, Chad M., Lueken, Ulrike, Veltman, Dick J., Winkler, Anderson M., Jahanshad, Neda, Pine, Daniel S., Thompson, Paul M., Stein, Dan J., and Van der Wee, Nic J. A.

Abstract

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE < 0.001; right: d = −0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.

Published
2023

46. Volume of subcortical brain regions in social anxiety disorder : mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group

Author

Groenewold, Nynke A., Bas-Hoogendam, Janna Marie, Amod, Alyssa R., Laansma, Max A., Van Velzen, Laura S., Aghajani, Moji, Hilbert, Kevin, Oh, Hyuntaek, Salas, Ramiro, Jackowski, Andrea P., Pan, Pedro M., Salum, Giovanni A., Blair, James R., Blair, Karina S., Hirsch, Joy, Pantazatos, Spiro P., Schneier, Franklin R., Talati, Ardesheer, Roelofs, Karin, Volman, Inge, Blanco-Hinojo, Laura, Cardoner, Narcís, Pujol, Jesus, Beesdo-Baum, Katja, Ching, Christopher R. K., Thomopoulos, Sophia I., Jansen, Andreas, Kircher, Tilo, Krug, Axel, Nenadić, Igor, Stein, Frederike, Dannlowski, Udo, Grotegerd, Dominik, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Erb, Michael, Kreifelts, Benjamin, Gong, Qiyong, Lui, Su, Zhu, Fei, Mwangi, Benson, Soares, Jair C., Wu, Mon-Ju, Bayram, Ali, Canli, Mesut, Tükel, Raşit, Westenberg, P. Michiel, Heeren, Alexandre, Cremers, Henk R., Hofmann, David, Straube, Thomas, Doruyter, Alexander G. G., Lochner, Christine, Peterburs, Jutta, Van Tol, Marie-José, Gur, Raquel E., Kaczkurkin, Antonia N., Larsen, Bart, Satterthwaite, Theodore D., Filippi, Courtney A., Gold, Andrea L., Harrewijn, Anita, Zugman, André, Bülow, Robin, Grabe, Hans J., Völzke, Henry, Wittfeld, Katharina, Böhnlein, Joscha, Dohm, Katharina, Kugel, Harald, Schrammen, Elisabeth, Zwanzger, Peter, Leehr, Elisabeth J., Sindermann, Lisa, Ball, Tali M., Fonzo, Gregory A., Paulus, Martin P., Simmons, Alan, Stein, Murray B., Klumpp, Heide, Phan, K. Luan, Furmark, Tomas, Månsson, Kristoffer N. T., Manzouri, Amirhossein, Avery, Suzanne N., Blackford, Jennifer Urbano, Clauss, Jacqueline A., Feola, Brandee, Harper, Jennifer C., Sylvester, Chad M., Lueken, Ulrike, Veltman, Dick J., Winkler, Anderson M., Jahanshad, Neda, Pine, Daniel S., Thompson, Paul M., Stein, Dan J., Van der Wee, Nic J. A., Groenewold, Nynke A., Bas-Hoogendam, Janna Marie, Amod, Alyssa R., Laansma, Max A., Van Velzen, Laura S., Aghajani, Moji, Hilbert, Kevin, Oh, Hyuntaek, Salas, Ramiro, Jackowski, Andrea P., Pan, Pedro M., Salum, Giovanni A., Blair, James R., Blair, Karina S., Hirsch, Joy, Pantazatos, Spiro P., Schneier, Franklin R., Talati, Ardesheer, Roelofs, Karin, Volman, Inge, Blanco-Hinojo, Laura, Cardoner, Narcís, Pujol, Jesus, Beesdo-Baum, Katja, Ching, Christopher R. K., Thomopoulos, Sophia I., Jansen, Andreas, Kircher, Tilo, Krug, Axel, Nenadić, Igor, Stein, Frederike, Dannlowski, Udo, Grotegerd, Dominik, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Erb, Michael, Kreifelts, Benjamin, Gong, Qiyong, Lui, Su, Zhu, Fei, Mwangi, Benson, Soares, Jair C., Wu, Mon-Ju, Bayram, Ali, Canli, Mesut, Tükel, Raşit, Westenberg, P. Michiel, Heeren, Alexandre, Cremers, Henk R., Hofmann, David, Straube, Thomas, Doruyter, Alexander G. G., Lochner, Christine, Peterburs, Jutta, Van Tol, Marie-José, Gur, Raquel E., Kaczkurkin, Antonia N., Larsen, Bart, Satterthwaite, Theodore D., Filippi, Courtney A., Gold, Andrea L., Harrewijn, Anita, Zugman, André, Bülow, Robin, Grabe, Hans J., Völzke, Henry, Wittfeld, Katharina, Böhnlein, Joscha, Dohm, Katharina, Kugel, Harald, Schrammen, Elisabeth, Zwanzger, Peter, Leehr, Elisabeth J., Sindermann, Lisa, Ball, Tali M., Fonzo, Gregory A., Paulus, Martin P., Simmons, Alan, Stein, Murray B., Klumpp, Heide, Phan, K. Luan, Furmark, Tomas, Månsson, Kristoffer N. T., Manzouri, Amirhossein, Avery, Suzanne N., Blackford, Jennifer Urbano, Clauss, Jacqueline A., Feola, Brandee, Harper, Jennifer C., Sylvester, Chad M., Lueken, Ulrike, Veltman, Dick J., Winkler, Anderson M., Jahanshad, Neda, Pine, Daniel S., Thompson, Paul M., Stein, Dan J., and Van der Wee, Nic J. A.

Abstract

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE < 0.001; right: d = −0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adul

Published
2023
Full Text
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47. Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium

Author

Onderzoek, Brain, Dwyer, Dominic B, Chand, Ganesh B, Pigoni, Alessandro, Khuntia, Adyasha, Wen, Junhao, Antoniades, Mathilde, Hwang, Gyujoon, Erus, Guray, Doshi, Jimit, Srinivasan, Dhivya, Varol, Erdem, Kahn, Rene S, Schnack, Hugo G, Meisenzahl, Eva, Wood, Stephen J, Zhuo, Chuanjun, Sotiras, Aristeidis, Shinohara, Russell T, Shou, Haochang, Fan, Yong, Schaulfelberger, Maristela, Rosa, Pedro, Lalousis, Paris A, Upthegrove, Rachel, Kaczkurkin, Antonia N, Moore, Tyler M, Nelson, Barnaby, Gur, Raquel E, Gur, Ruben C, Ritchie, Marylyn D, Satterthwaite, Theodore D, Murray, Robin M, Di Forti, Marta, Ciufolini, Simone, Zanetti, Marcus V, Wolf, Daniel H, Pantelis, Christos, Crespo-Facorro, Benedicto, Busatto, Geraldo F, Davatzikos, Christos, Koutsouleris, Nikolaos, Dazzan, Paola, Onderzoek, Brain, Dwyer, Dominic B, Chand, Ganesh B, Pigoni, Alessandro, Khuntia, Adyasha, Wen, Junhao, Antoniades, Mathilde, Hwang, Gyujoon, Erus, Guray, Doshi, Jimit, Srinivasan, Dhivya, Varol, Erdem, Kahn, Rene S, Schnack, Hugo G, Meisenzahl, Eva, Wood, Stephen J, Zhuo, Chuanjun, Sotiras, Aristeidis, Shinohara, Russell T, Shou, Haochang, Fan, Yong, Schaulfelberger, Maristela, Rosa, Pedro, Lalousis, Paris A, Upthegrove, Rachel, Kaczkurkin, Antonia N, Moore, Tyler M, Nelson, Barnaby, Gur, Raquel E, Gur, Ruben C, Ritchie, Marylyn D, Satterthwaite, Theodore D, Murray, Robin M, Di Forti, Marta, Ciufolini, Simone, Zanetti, Marcus V, Wolf, Daniel H, Pantelis, Christos, Crespo-Facorro, Benedicto, Busatto, Geraldo F, Davatzikos, Christos, Koutsouleris, Nikolaos, and Dazzan, Paola

Published
2023

48. Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium

Author

National Institutes of Health (US), National Health and Medical Research Council (Australia), Council of Australian University Librarians, Dwyer, Dominic B., Chand, Ganesh B., Pigoni, Alessandro, Khuntia, Adyasha, Wen, Junhao, Antoniades, Mathilde, Hwang, Gyujoon, Erus, Guray, Doshi, Jimit, Srinivasan, Dhivya, Varol, Erdem, Kahn, Rene S., Schnack, Hugo G., Meisenzahl, Eva, Wood, Stephen J., Zhuo, Chuanjun, Sotiras, Aristeidis, Shinohara, Russell T., Shou, Haochang, Fan, Yong, Schaulfelberger, Maristela, Rosa, Pedro, Lalousis, Paris A., Upthegrove, Rachel, Kaczkurkin, Antonia N., Moore, Tyler M., Nelson, Barnaby, Gur, Rachel E., Gur, Ruben C., Ritchie, Marylyn D., Satterthwaite, Theodore D., Murray, Robin M., Forti, Marta Di, Ciufolini, Simone, Zanetti, Marcus V., Wolf, Daniel H., Pantelis, Christos, Crespo-Facorro, Benedicto, Busatto, Geraldo F., Davatzikos, Christos, Koutsouleris, Nikolaos, Dazzan, Paola, National Institutes of Health (US), National Health and Medical Research Council (Australia), Council of Australian University Librarians, Dwyer, Dominic B., Chand, Ganesh B., Pigoni, Alessandro, Khuntia, Adyasha, Wen, Junhao, Antoniades, Mathilde, Hwang, Gyujoon, Erus, Guray, Doshi, Jimit, Srinivasan, Dhivya, Varol, Erdem, Kahn, Rene S., Schnack, Hugo G., Meisenzahl, Eva, Wood, Stephen J., Zhuo, Chuanjun, Sotiras, Aristeidis, Shinohara, Russell T., Shou, Haochang, Fan, Yong, Schaulfelberger, Maristela, Rosa, Pedro, Lalousis, Paris A., Upthegrove, Rachel, Kaczkurkin, Antonia N., Moore, Tyler M., Nelson, Barnaby, Gur, Rachel E., Gur, Ruben C., Ritchie, Marylyn D., Satterthwaite, Theodore D., Murray, Robin M., Forti, Marta Di, Ciufolini, Simone, Zanetti, Marcus V., Wolf, Daniel H., Pantelis, Christos, Crespo-Facorro, Benedicto, Busatto, Geraldo F., Davatzikos, Christos, Koutsouleris, Nikolaos, and Dazzan, Paola

Abstract

Using machine learning, we recently decomposed the neuroanatomical heterogeneity of established schizophrenia to discover two volumetric subgroups—a ‘lower brain volume’ subgroup (SG1) and an ‘higher striatal volume’ subgroup (SG2) with otherwise normal brain structure. In this study, we investigated whether the MRI signatures of these subgroups were also already present at the time of the first-episode of psychosis (FEP) and whether they were related to clinical presentation and clinical remission over 1-, 3-, and 5-years. We included 572 FEP and 424 healthy controls (HC) from 4 sites (Sao Paulo, Santander, London, Melbourne) of the PHENOM consortium. Our prior MRI subgrouping models (671 participants; USA, Germany, and China) were applied to both FEP and HC. Participants were assigned into 1 of 4 categories: subgroup 1 (SG1), subgroup 2 (SG2), no subgroup membership (‘None’), and mixed SG1 + SG2 subgroups (‘Mixed’). Voxel-wise analyses characterized SG1 and SG2 subgroups. Supervised machine learning analyses characterized baseline and remission signatures related to SG1 and SG2 membership. The two dominant patterns of ‘lower brain volume’ in SG1 and ‘higher striatal volume’ (with otherwise normal neuromorphology) in SG2 were identified already at the first episode of psychosis. SG1 had a significantly higher proportion of FEP (32%) vs. HC (19%) than SG2 (FEP, 21%; HC, 23%). Clinical multivariate signatures separated the SG1 and SG2 subgroups (balanced accuracy = 64%; p < 0.0001), with SG2 showing higher education but also greater positive psychosis symptoms at first presentation, and an association with symptom remission at 1-year, 5-year, and when timepoints were combined. Neuromorphological subtypes of schizophrenia are already evident at illness onset, separated by distinct clinical presentations, and differentially associated with subsequent remission. These results suggest that the subgroups may be underlying risk phenotypes that could be targeted in future t

Published
2023

49. Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group

Author

Groenewold, Nynke A, Bas-Hoogendam, Janna Marie, Amod, Alyssa R, Laansma, Max A, Van Velzen, Laura S, Aghajani, Moji, Hilbert, Kevin, Oh, Hyuntaek, Salas, Ramiro, Jackowski, Andrea P, Pan, Pedro M, Salum, Giovanni A, Blair, James R, Blair, Karina S, Hirsch, Joy, Pantazatos, Spiro P, Schneier, Franklin R, Talati, Ardesheer, Roelofs, Karin, Volman, Inge, Blanco-Hinojo, Laura, Cardoner, Narcís, Pujol, Jesus, Beesdo-Baum, Katja, Ching, Christopher R K, Thomopoulos, Sophia I, Jansen, Andreas, Kircher, Tilo, Krug, Axel, Nenadić, Igor, Stein, Frederike, Dannlowski, Udo, Grotegerd, Dominik, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Erb, Michael, Kreifelts, Benjamin, Gong, Qiyong, Lui, Su, Zhu, Fei, Mwangi, Benson, Soares, Jair C, Wu, Mon-Ju, Bayram, Ali, Canli, Mesut, Tükel, Raşit, Westenberg, P Michiel, Heeren, Alexandre, Cremers, Henk R, Hofmann, David, Straube, Thomas, Doruyter, Alexander G G, Lochner, Christine, Peterburs, Jutta, Van Tol, Marie-José, Gur, Raquel E, Kaczkurkin, Antonia N, Larsen, Bart, Satterthwaite, Theodore D, Filippi, Courtney A, Gold, Andrea L, Harrewijn, Anita, Zugman, André, Bülow, Robin, Grabe, Hans J, Völzke, Henry, Wittfeld, Katharina, Böhnlein, Joscha, Dohm, Katharina, Kugel, Harald, Schrammen, Elisabeth, Zwanzger, Peter, Leehr, Elisabeth J, Sindermann, Lisa, Ball, Tali M, Fonzo, Gregory A, Paulus, Martin P, Simmons, Alan, Stein, Murray B, Klumpp, Heide, Phan, K Luan, Furmark, Tomas, Månsson, Kristoffer N T, Manzouri, Amirhossein, Avery, Suzanne N, Blackford, Jennifer Urbano, Clauss, Jacqueline A, Feola, Brandee, Harper, Jennifer C, Sylvester, Chad M, Lueken, Ulrike, Veltman, Dick J, Winkler, Anderson M, Jahanshad, Neda, Pine, Daniel S, Thompson, Paul M, Stein, Dan J, Van der Wee, Nic J A, Groenewold, Nynke A, Bas-Hoogendam, Janna Marie, Amod, Alyssa R, Laansma, Max A, Van Velzen, Laura S, Aghajani, Moji, Hilbert, Kevin, Oh, Hyuntaek, Salas, Ramiro, Jackowski, Andrea P, Pan, Pedro M, Salum, Giovanni A, Blair, James R, Blair, Karina S, Hirsch, Joy, Pantazatos, Spiro P, Schneier, Franklin R, Talati, Ardesheer, Roelofs, Karin, Volman, Inge, Blanco-Hinojo, Laura, Cardoner, Narcís, Pujol, Jesus, Beesdo-Baum, Katja, Ching, Christopher R K, Thomopoulos, Sophia I, Jansen, Andreas, Kircher, Tilo, Krug, Axel, Nenadić, Igor, Stein, Frederike, Dannlowski, Udo, Grotegerd, Dominik, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Erb, Michael, Kreifelts, Benjamin, Gong, Qiyong, Lui, Su, Zhu, Fei, Mwangi, Benson, Soares, Jair C, Wu, Mon-Ju, Bayram, Ali, Canli, Mesut, Tükel, Raşit, Westenberg, P Michiel, Heeren, Alexandre, Cremers, Henk R, Hofmann, David, Straube, Thomas, Doruyter, Alexander G G, Lochner, Christine, Peterburs, Jutta, Van Tol, Marie-José, Gur, Raquel E, Kaczkurkin, Antonia N, Larsen, Bart, Satterthwaite, Theodore D, Filippi, Courtney A, Gold, Andrea L, Harrewijn, Anita, Zugman, André, Bülow, Robin, Grabe, Hans J, Völzke, Henry, Wittfeld, Katharina, Böhnlein, Joscha, Dohm, Katharina, Kugel, Harald, Schrammen, Elisabeth, Zwanzger, Peter, Leehr, Elisabeth J, Sindermann, Lisa, Ball, Tali M, Fonzo, Gregory A, Paulus, Martin P, Simmons, Alan, Stein, Murray B, Klumpp, Heide, Phan, K Luan, Furmark, Tomas, Månsson, Kristoffer N T, Manzouri, Amirhossein, Avery, Suzanne N, Blackford, Jennifer Urbano, Clauss, Jacqueline A, Feola, Brandee, Harper, Jennifer C, Sylvester, Chad M, Lueken, Ulrike, Veltman, Dick J, Winkler, Anderson M, Jahanshad, Neda, Pine, Daniel S, Thompson, Paul M, Stein, Dan J, and Van der Wee, Nic J A

Abstract

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, p FWE = 0.037; right: d = -0.104, p FWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, p FWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, p FWE < 0.001; right: d = -0.158, p FWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, p FWE = 0.006; right: d = 0.099, p FWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adol

Published
2023

50. Elevated Amygdala Perfusion Mediates Developmental Sex Differences in Trait Anxiety

Author

Kaczkurkin, Antonia N., Moore, Tyler M., Ruparel, Kosha, Ciric, Rastko, Calkins, Monica E., Shinohara, Russell T., Elliott, Mark A., Hopson, Ryan, Roalf, David R., Vandekar, Simon N., Gennatas, Efstathios D., Wolf, Daniel H., Scott, J. Cobb, Pine, Daniel S., Leibenluft, Ellen, Detre, John A., Foa, Edna B., Gur, Raquel E., Gur, Ruben C., and Satterthwaite, Theodore D.

Published
2016
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