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.
Original language | English (US) |
---|---|
Pages (from-to) | 1079-1089 |
Number of pages | 11 |
Journal | Molecular Psychiatry |
Volume | 28 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2023 |
Externally published | Yes |
ASJC Scopus subject areas
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Molecular Biology
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In: Molecular Psychiatry, Vol. 28, No. 3, 03.2023, p. 1079-1089.
Research output: Contribution to journal › Article › peer-review
}
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 -