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

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

doi:10.1038/s41380-022-01933-9

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

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

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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 adolescence into adulthood.

Original language	English (US)
Pages (from-to)	1079-1089
Number of pages	11
Journal	Molecular Psychiatry
Volume	28
Issue number	3
DOIs	https://doi.org/10.1038/s41380-022-01933-9
State	Published - Mar 2023
Externally published	Yes

ASJC Scopus subject areas

Psychiatry and Mental health
Cellular and Molecular Neuroscience
Molecular Biology

Access to Document

10.1038/s41380-022-01933-9

Cite this

Groenewold, N. A., Bas-Hoogendam, J. M., Amod, A. R., Laansma, M. A., Van Velzen, L. S., Aghajani, M., Hilbert, K., Oh, H., Salas, R., Jackowski, A. P., Pan, P. M., Salum, G. A., Blair, J. R., Blair, K. S., Hirsch, J., Pantazatos, S. P., Schneier, F. R., Talati, A., Roelofs, K., ... Van der Wee, N. J. A. (2023). Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group. Molecular Psychiatry, 28(3), 1079-1089. https://doi.org/10.1038/s41380-022-01933-9

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, MJ, Bayram, A, Canli, M, Tükel, R, Westenberg, PM, Heeren, A, Cremers, HR, Hofmann, D, Straube, T, Doruyter, AGG, Lochner, C, Peterburs, J, Van Tol, MJ, 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 2023, 'Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group', Molecular Psychiatry, vol. 28, no. 3, pp. 1079-1089. https://doi.org/10.1038/s41380-022-01933-9

@article{8c0a0075f92044cbbf9755e4d303594b,

title = "Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group",

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.",

author = "Groenewold, {Nynke A.} and Bas-Hoogendam, {Janna Marie} and Amod, {Alyssa R.} and Laansma, {Max A.} and {Van Velzen}, {Laura S.} and Moji Aghajani and Kevin Hilbert and Hyuntaek Oh and Ramiro Salas and Jackowski, {Andrea P.} and Pan, {Pedro M.} and Salum, {Giovanni A.} and Blair, {James R.} and Blair, {Karina S.} and Joy Hirsch and Pantazatos, {Spiro P.} and Schneier, {Franklin R.} and Ardesheer Talati and Karin Roelofs and Inge Volman and Laura Blanco-Hinojo and Narc{\'i}s Cardoner and Jesus Pujol and Katja Beesdo-Baum and Ching, {Christopher R.K.} and Thomopoulos, {Sophia I.} and Andreas Jansen and Tilo Kircher and Axel Krug and Igor Nenadi{\'c} and Frederike Stein and Udo Dannlowski and Dominik Grotegerd and Hannah Lemke and Susanne Meinert and Alexandra Winter and Michael Erb and Benjamin Kreifelts and Qiyong Gong and Su Lui and Fei Zhu and Benson Mwangi and Soares, {Jair C.} and Wu, {Mon Ju} and Ali Bayram and Mesut Canli and Ra{\c s}it T{\"u}kel and Westenberg, {P. Michiel} and Alexandre Heeren and Cremers, {Henk R.} and David Hofmann and Thomas Straube and Doruyter, {Alexander G.G.} and Christine Lochner and Jutta Peterburs and {Van Tol}, {Marie Jos{\'e}} and Gur, {Raquel E.} and Kaczkurkin, {Antonia N.} and Bart Larsen and Satterthwaite, {Theodore D.} and Filippi, {Courtney A.} and Gold, {Andrea L.} and Anita Harrewijn and Andr{\'e} Zugman and Robin B{\"u}low and Grabe, {Hans J.} and Henry V{\"o}lzke and Katharina Wittfeld and Joscha B{\"o}hnlein and Katharina Dohm and Harald Kugel and Elisabeth Schrammen and Peter Zwanzger and Leehr, {Elisabeth J.} and Lisa Sindermann and Ball, {Tali M.} and Fonzo, {Gregory A.} and Paulus, {Martin P.} and Alan Simmons and Stein, {Murray B.} and Heide Klumpp and Phan, {K. Luan} and Tomas Furmark and M{\aa}nsson, {Kristoffer N.T.} and Amirhossein Manzouri and Avery, {Suzanne N.} and Blackford, {Jennifer Urbano} and Clauss, {Jacqueline A.} and Brandee Feola and Harper, {Jennifer C.} and Sylvester, {Chad M.} and Ulrike Lueken and Veltman, {Dick J.} and Winkler, {Anderson M.} and Neda Jahanshad and Pine, {Daniel S.} and Thompson, {Paul M.} and Stein, {Dan J.} and {Van der Wee}, {Nic J.A.}",

note = "Funding Information: ENIGMA acknowledges the NIH Big Data to Knowledge (BD2K) award for foundational support and consortium development (U54 EB020403 to PMT). For a complete list of ENIGMA-related grant support please see here: http://enigma.ini.usc.edu/about-2/funding/. NAG was supported by a Developing Emerging Academic Leaders Fellowship. This work was made possible in part by a grant from Carnegie Corporation of New York. JMBH was supported by a Rubicon grant from the Dutch Research Council NWO (019.201SG.022). ARA, CL, and DJS were supported by the South African Medical Research Council (SA-MRC). DJS and NJAW were supported by the EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant “European and South African Research Network in Anxiety Disorders” (EUSARNAD). NJAW was also supported by the Anxiety Disorders Research Network European College of Neuropsychopharmacology. The Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) was funded by Leiden University Research Profile {\textquoteleft}Health, Prevention and the Human Life Cycle{\textquoteright}. The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (ZonMw, grant number 10-000-1002) and financial contributions by participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Leiden University Medical Center, Leiden University, GGZ Rivierduinen, University Medical Center Groningen, University of Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Rob Giel Onderzoekscentrum). SHIP is part of the Community Medicine Research Network of the University Medicine Greifswald, which is supported by the German Ministry of Education and Research (BMBF) and a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania. This work was supported by multiple grants from the German Research Foundation (DFG): FOR5187 grant (HI 2189/4-1) - KH; grant BE 3809/8-1 - KBB, grants (JA 1890/7-1, JA 1890/7-2) - AJ; grants FOR2107 (KI588/14-1, KI588/14-2) - TK; grants (KR 3822/7-1, KR 3822/7-2) -AK; grants (NE2254/1-2, NE2254/3-1, NE2254/4-1) - IN; grants (DA1151/5-1, DA1151/5-2) - UD; FOR5187 grant (KR 4398/5-1) - BK; (SFB/TRR 58: C06, C07) - TS; grants (LU 1509/9-1, LU 1509/10-1, LU 1509/11-1) - UL. UD was additionally supported by the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of M{\"u}nster (grant Dan3/012/17 to UD). This work was further supported by the NIH through multiple grants. MPP, MBS, TMB and AS were supported by NIMH MH65413. GAF was supported by NIMH K23MH114023 and JUB was supported by NIMH K01MH083052. JAC was supported by NIMH 5T32MH112485. BF was supported by NIMH T32MH018921. CMS was supported by NIMH K23MH109983 and R01MH122389. NJ was supported by R01MH117601. DSP was supported by ZIA-MH-002781. In addition, GAF received support from the One Mind – Basczucki Brain Research Fund. JAC was additionally supported by the Louis V. Gerstner III Research Scholar Award. HO was supported by the American Foundation for Suicide Prevention (YIG-1-141-20). RS was supported by the McNair Foundation (MIND-MB), VHA (CX000994, CX001937). PMP was supported by the foundation for Research Support of the State of S{\~a}o Paulo (FAPESP 2014 / 50917-0), Brazil and the National Council for Scientific and Technological Development CNPq 465550/2014-2), Brazil. AT was supported by NARSAD/Brain and Behavioral Research Foundation. KR was supported by the European Research Council (grant# ERC_CoG-2017_772337). QG was supported by the National Natural Science Foundation of China (Project Nos. 82120108014 and 81621003). SL acknowledges the support from Humboldt Foundation Friedrich Wilhelm Bessel Research Award. AH (Louvain) was supported by the F.R.S.-FNRS Belgian Science Foundation (Grant ”1.C.059.18 F”) and by the Belgian Fund for Scientific Research (F.R.S.-FNRS, Belgium) as Research Associate. AGGD was funded by the SA-MRC under the MRC Clinician Researcher Programme; the National Technologies in Medicine and the Biosciences Initiative (NTeMBI), managed by the South African Nuclear Energy Corporation (Necsa) and funded by the Department of Science and Innovation; and Harry Crossley Foundation. TF was supported by the Swedish Research Council, the Swedish Brain Foundation, and Riksbankens Jubileumsfond. KNTM was supported by the Swedish Research Council (2018-06729). Funding Information: ENIGMA acknowledges the NIH Big Data to Knowledge (BD2K) award for foundational support and consortium development (U54 EB020403 to PMT). For a complete list of ENIGMA-related grant support please see here: http://enigma.ini.usc.edu/about-2/funding/ . NAG was supported by a Developing Emerging Academic Leaders Fellowship. This work was made possible in part by a grant from Carnegie Corporation of New York. JMBH was supported by a Rubicon grant from the Dutch Research Council NWO (019.201SG.022). ARA, CL, and DJS were supported by the South African Medical Research Council (SA-MRC). DJS and NJAW were supported by the EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant “European and South African Research Network in Anxiety Disorders” (EUSARNAD). NJAW was also supported by the Anxiety Disorders Research Network European College of Neuropsychopharmacology. The Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) was funded by Leiden University Research Profile {\textquoteleft}Health, Prevention and the Human Life Cycle{\textquoteright}. The infrastructure for the NESDA study ( www.nesda.nl ) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (ZonMw, grant number 10-000-1002) and financial contributions by participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Leiden University Medical Center, Leiden University, GGZ Rivierduinen, University Medical Center Groningen, University of Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Rob Giel Onderzoekscentrum). SHIP is part of the Community Medicine Research Network of the University Medicine Greifswald, which is supported by the German Ministry of Education and Research (BMBF) and a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania. This work was supported by multiple grants from the German Research Foundation (DFG): FOR5187 grant (HI 2189/4-1) - KH; grant BE 3809/8-1 - KBB, grants (JA 1890/7-1, JA 1890/7-2) - AJ; grants FOR2107 (KI588/14-1, KI588/14-2) - TK; grants (KR 3822/7-1, KR 3822/7-2) -AK; grants (NE2254/1-2, NE2254/3-1, NE2254/4-1) - IN; grants (DA1151/5-1, DA1151/5-2) - UD; FOR5187 grant (KR 4398/5-1) - BK; (SFB/TRR 58: C06, C07) - TS; grants (LU 1509/9-1, LU 1509/10-1, LU 1509/11-1) - UL. UD was additionally supported by the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of M{\"u}nster (grant Dan3/012/17 to UD). This work was further supported by the NIH through multiple grants. MPP, MBS, TMB and AS were supported by NIMH MH65413. GAF was supported by NIMH K23MH114023 and JUB was supported by NIMH K01MH083052. JAC was supported by NIMH 5T32MH112485. BF was supported by NIMH T32MH018921. CMS was supported by NIMH K23MH109983 and R01MH122389. NJ was supported by R01MH117601. DSP was supported by ZIA-MH-002781. In addition, GAF received support from the One Mind – Basczucki Brain Research Fund. JAC was additionally supported by the Louis V. Gerstner III Research Scholar Award. HO was supported by the American Foundation for Suicide Prevention (YIG-1-141-20). RS was supported by the McNair Foundation (MIND-MB), VHA (CX000994, CX001937). PMP was supported by the foundation for Research Support of the State of S{\~a}o Paulo (FAPESP 2014 / 50917-0), Brazil and the National Council for Scientific and Technological Development CNPq 465550/2014-2), Brazil. AT was supported by NARSAD/Brain and Behavioral Research Foundation. KR was supported by the European Research Council (grant# ERC_CoG-2017_772337). QG was supported by the National Natural Science Foundation of China (Project Nos. 82120108014 and 81621003). SL acknowledges the support from Humboldt Foundation Friedrich Wilhelm Bessel Research Award. AH (Louvain) was supported by the F.R.S.-FNRS Belgian Science Foundation (Grant ”1.C.059.18 F”) and by the Belgian Fund for Scientific Research (F.R.S.-FNRS, Belgium) as Research Associate. AGGD was funded by the SA-MRC under the MRC Clinician Researcher Programme; the National Technologies in Medicine and the Biosciences Initiative (NTeMBI), managed by the South African Nuclear Energy Corporation (Necsa) and funded by the Department of Science and Innovation; and Harry Crossley Foundation. TF was supported by the Swedish Research Council, the Swedish Brain Foundation, and Riksbankens Jubileumsfond. KNTM was supported by the Swedish Research Council (2018-06729). Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2023",

month = mar,

doi = "10.1038/s41380-022-01933-9",

language = "English (US)",

volume = "28",

pages = "1079--1089",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Nature Publishing Group",

number = "3",

}

TY - JOUR

T1 - Volume of subcortical brain regions in social anxiety disorder

T2 - mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group

AU - Groenewold, Nynke A.

AU - Bas-Hoogendam, Janna Marie

AU - Amod, Alyssa R.

AU - Laansma, Max A.

AU - Van Velzen, Laura S.

AU - Aghajani, Moji

AU - Hilbert, Kevin

AU - Oh, Hyuntaek

AU - Salas, Ramiro

AU - Jackowski, Andrea P.

AU - Pan, Pedro M.

AU - Salum, Giovanni A.

AU - Blair, James R.

AU - Blair, Karina S.

AU - Hirsch, Joy

AU - Pantazatos, Spiro P.

AU - Schneier, Franklin R.

AU - Talati, Ardesheer

AU - Roelofs, Karin

AU - Volman, Inge

AU - Blanco-Hinojo, Laura

AU - Cardoner, Narcís

AU - Pujol, Jesus

AU - Beesdo-Baum, Katja

AU - Ching, Christopher R.K.

AU - Thomopoulos, Sophia I.

AU - Jansen, Andreas

AU - Kircher, Tilo

AU - Krug, Axel

AU - Nenadić, Igor

AU - Stein, Frederike

AU - Dannlowski, Udo

AU - Grotegerd, Dominik

AU - Lemke, Hannah

AU - Meinert, Susanne

AU - Winter, Alexandra

AU - Erb, Michael

AU - Kreifelts, Benjamin

AU - Gong, Qiyong

AU - Lui, Su

AU - Zhu, Fei

AU - Mwangi, Benson

AU - Soares, Jair C.

AU - Wu, Mon Ju

AU - Bayram, Ali

AU - Canli, Mesut

AU - Tükel, Raşit

AU - Westenberg, P. Michiel

AU - Heeren, Alexandre

AU - Cremers, Henk R.

AU - Hofmann, David

AU - Straube, Thomas

AU - Doruyter, Alexander G.G.

AU - Lochner, Christine

AU - Peterburs, Jutta

AU - Van Tol, Marie José

AU - Gur, Raquel E.

AU - Kaczkurkin, Antonia N.

AU - Larsen, Bart

AU - Satterthwaite, Theodore D.

AU - Filippi, Courtney A.

AU - Gold, Andrea L.

AU - Harrewijn, Anita

AU - Zugman, André

AU - Bülow, Robin

AU - Grabe, Hans J.

AU - Völzke, Henry

AU - Wittfeld, Katharina

AU - Böhnlein, Joscha

AU - Dohm, Katharina

AU - Kugel, Harald

AU - Schrammen, Elisabeth

AU - Zwanzger, Peter

AU - Leehr, Elisabeth J.

AU - Sindermann, Lisa

AU - Ball, Tali M.

AU - Fonzo, Gregory A.

AU - Paulus, Martin P.

AU - Simmons, Alan

AU - Stein, Murray B.

AU - Klumpp, Heide

AU - Phan, K. Luan

AU - Furmark, Tomas

AU - Månsson, Kristoffer N.T.

AU - Manzouri, Amirhossein

AU - Avery, Suzanne N.

AU - Blackford, Jennifer Urbano

AU - Clauss, Jacqueline A.

AU - Feola, Brandee

AU - Harper, Jennifer C.

AU - Sylvester, Chad M.

AU - Lueken, Ulrike

AU - Veltman, Dick J.

AU - Winkler, Anderson M.

AU - Jahanshad, Neda

AU - Pine, Daniel S.

AU - Thompson, Paul M.

AU - Stein, Dan J.

AU - Van der Wee, Nic J.A.

N1 - Funding Information: ENIGMA acknowledges the NIH Big Data to Knowledge (BD2K) award for foundational support and consortium development (U54 EB020403 to PMT). For a complete list of ENIGMA-related grant support please see here: http://enigma.ini.usc.edu/about-2/funding/. NAG was supported by a Developing Emerging Academic Leaders Fellowship. This work was made possible in part by a grant from Carnegie Corporation of New York. JMBH was supported by a Rubicon grant from the Dutch Research Council NWO (019.201SG.022). ARA, CL, and DJS were supported by the South African Medical Research Council (SA-MRC). DJS and NJAW were supported by the EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant “European and South African Research Network in Anxiety Disorders” (EUSARNAD). NJAW was also supported by the Anxiety Disorders Research Network European College of Neuropsychopharmacology. The Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) was funded by Leiden University Research Profile ‘Health, Prevention and the Human Life Cycle’. The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (ZonMw, grant number 10-000-1002) and financial contributions by participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Leiden University Medical Center, Leiden University, GGZ Rivierduinen, University Medical Center Groningen, University of Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Rob Giel Onderzoekscentrum). SHIP is part of the Community Medicine Research Network of the University Medicine Greifswald, which is supported by the German Ministry of Education and Research (BMBF) and a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania. This work was supported by multiple grants from the German Research Foundation (DFG): FOR5187 grant (HI 2189/4-1) - KH; grant BE 3809/8-1 - KBB, grants (JA 1890/7-1, JA 1890/7-2) - AJ; grants FOR2107 (KI588/14-1, KI588/14-2) - TK; grants (KR 3822/7-1, KR 3822/7-2) -AK; grants (NE2254/1-2, NE2254/3-1, NE2254/4-1) - IN; grants (DA1151/5-1, DA1151/5-2) - UD; FOR5187 grant (KR 4398/5-1) - BK; (SFB/TRR 58: C06, C07) - TS; grants (LU 1509/9-1, LU 1509/10-1, LU 1509/11-1) - UL. UD was additionally supported by the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant Dan3/012/17 to UD). This work was further supported by the NIH through multiple grants. MPP, MBS, TMB and AS were supported by NIMH MH65413. GAF was supported by NIMH K23MH114023 and JUB was supported by NIMH K01MH083052. JAC was supported by NIMH 5T32MH112485. BF was supported by NIMH T32MH018921. CMS was supported by NIMH K23MH109983 and R01MH122389. NJ was supported by R01MH117601. DSP was supported by ZIA-MH-002781. In addition, GAF received support from the One Mind – Basczucki Brain Research Fund. JAC was additionally supported by the Louis V. Gerstner III Research Scholar Award. HO was supported by the American Foundation for Suicide Prevention (YIG-1-141-20). RS was supported by the McNair Foundation (MIND-MB), VHA (CX000994, CX001937). PMP was supported by the foundation for Research Support of the State of São Paulo (FAPESP 2014 / 50917-0), Brazil and the National Council for Scientific and Technological Development CNPq 465550/2014-2), Brazil. AT was supported by NARSAD/Brain and Behavioral Research Foundation. KR was supported by the European Research Council (grant# ERC_CoG-2017_772337). QG was supported by the National Natural Science Foundation of China (Project Nos. 82120108014 and 81621003). SL acknowledges the support from Humboldt Foundation Friedrich Wilhelm Bessel Research Award. AH (Louvain) was supported by the F.R.S.-FNRS Belgian Science Foundation (Grant ”1.C.059.18 F”) and by the Belgian Fund for Scientific Research (F.R.S.-FNRS, Belgium) as Research Associate. AGGD was funded by the SA-MRC under the MRC Clinician Researcher Programme; the National Technologies in Medicine and the Biosciences Initiative (NTeMBI), managed by the South African Nuclear Energy Corporation (Necsa) and funded by the Department of Science and Innovation; and Harry Crossley Foundation. TF was supported by the Swedish Research Council, the Swedish Brain Foundation, and Riksbankens Jubileumsfond. KNTM was supported by the Swedish Research Council (2018-06729). Funding Information: ENIGMA acknowledges the NIH Big Data to Knowledge (BD2K) award for foundational support and consortium development (U54 EB020403 to PMT). For a complete list of ENIGMA-related grant support please see here: http://enigma.ini.usc.edu/about-2/funding/ . NAG was supported by a Developing Emerging Academic Leaders Fellowship. This work was made possible in part by a grant from Carnegie Corporation of New York. JMBH was supported by a Rubicon grant from the Dutch Research Council NWO (019.201SG.022). ARA, CL, and DJS were supported by the South African Medical Research Council (SA-MRC). DJS and NJAW were supported by the EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant “European and South African Research Network in Anxiety Disorders” (EUSARNAD). NJAW was also supported by the Anxiety Disorders Research Network European College of Neuropsychopharmacology. The Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) was funded by Leiden University Research Profile ‘Health, Prevention and the Human Life Cycle’. The infrastructure for the NESDA study ( www.nesda.nl ) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (ZonMw, grant number 10-000-1002) and financial contributions by participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Leiden University Medical Center, Leiden University, GGZ Rivierduinen, University Medical Center Groningen, University of Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Rob Giel Onderzoekscentrum). SHIP is part of the Community Medicine Research Network of the University Medicine Greifswald, which is supported by the German Ministry of Education and Research (BMBF) and a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania. This work was supported by multiple grants from the German Research Foundation (DFG): FOR5187 grant (HI 2189/4-1) - KH; grant BE 3809/8-1 - KBB, grants (JA 1890/7-1, JA 1890/7-2) - AJ; grants FOR2107 (KI588/14-1, KI588/14-2) - TK; grants (KR 3822/7-1, KR 3822/7-2) -AK; grants (NE2254/1-2, NE2254/3-1, NE2254/4-1) - IN; grants (DA1151/5-1, DA1151/5-2) - UD; FOR5187 grant (KR 4398/5-1) - BK; (SFB/TRR 58: C06, C07) - TS; grants (LU 1509/9-1, LU 1509/10-1, LU 1509/11-1) - UL. UD was additionally supported by the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant Dan3/012/17 to UD). This work was further supported by the NIH through multiple grants. MPP, MBS, TMB and AS were supported by NIMH MH65413. GAF was supported by NIMH K23MH114023 and JUB was supported by NIMH K01MH083052. JAC was supported by NIMH 5T32MH112485. BF was supported by NIMH T32MH018921. CMS was supported by NIMH K23MH109983 and R01MH122389. NJ was supported by R01MH117601. DSP was supported by ZIA-MH-002781. In addition, GAF received support from the One Mind – Basczucki Brain Research Fund. JAC was additionally supported by the Louis V. Gerstner III Research Scholar Award. HO was supported by the American Foundation for Suicide Prevention (YIG-1-141-20). RS was supported by the McNair Foundation (MIND-MB), VHA (CX000994, CX001937). PMP was supported by the foundation for Research Support of the State of São Paulo (FAPESP 2014 / 50917-0), Brazil and the National Council for Scientific and Technological Development CNPq 465550/2014-2), Brazil. AT was supported by NARSAD/Brain and Behavioral Research Foundation. KR was supported by the European Research Council (grant# ERC_CoG-2017_772337). QG was supported by the National Natural Science Foundation of China (Project Nos. 82120108014 and 81621003). SL acknowledges the support from Humboldt Foundation Friedrich Wilhelm Bessel Research Award. AH (Louvain) was supported by the F.R.S.-FNRS Belgian Science Foundation (Grant ”1.C.059.18 F”) and by the Belgian Fund for Scientific Research (F.R.S.-FNRS, Belgium) as Research Associate. AGGD was funded by the SA-MRC under the MRC Clinician Researcher Programme; the National Technologies in Medicine and the Biosciences Initiative (NTeMBI), managed by the South African Nuclear Energy Corporation (Necsa) and funded by the Department of Science and Innovation; and Harry Crossley Foundation. TF was supported by the Swedish Research Council, the Swedish Brain Foundation, and Riksbankens Jubileumsfond. KNTM was supported by the Swedish Research Council (2018-06729). Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2023/3

Y1 - 2023/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85146389629&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85146389629&partnerID=8YFLogxK

U2 - 10.1038/s41380-022-01933-9

DO - 10.1038/s41380-022-01933-9

M3 - Article

C2 - 36653677

AN - SCOPUS:85146389629

SN - 1359-4184

VL - 28

SP - 1079

EP - 1089

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 3

ER -

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

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