Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group

Esther Walton; Fabio Bernardoni; Victoria Luise Batury; Klaas Bahnsen; Sara Larivière; Giovanni Abbate-Daga; Susana Andres-Perpiña; Lasse Bang; Amanda Bischoff-Grethe; Samantha J. Brooks; Iain C. Campbell; Giammarco Cascino; Josefina Castro-Fornieles; Enrico Collantoni; Federico D'Agata; Brigitte Dahmen; Unna N. Danner; Angela Favaro; Jamie D. Feusner; Guido K.W. Frank; Hans Christoph Friederich; John L. Graner; Beate Herpertz-Dahlmann; Andreas Hess; Stefanie Horndasch; Allan S. Kaplan; Lisa Katrin Kaufmann; Walter H. Kaye; Sahib S. Khalsa; Kevin S. LaBar; Luca Lavagnino; Luisa Lazaro; Renzo Manara; Amy E. Miles; Gabriella F. Milos; Alessio Maria Monteleone; Palmiero Monteleone; Benson Mwangi; Owen O'Daly; Jose Pariente; Julie Roesch; Ulrike H. Schmidt; Jochen Seitz; Megan E. Shott; Joe J. Simon; Paul A.M. Smeets; Christian K. Tamnes; Elena Tenconi; Sophia I. Thomopoulos; Annemarie A. van Elburg; Aristotle N. Voineskos; Georg G. von Polier; Christina E. Wierenga; Nancy L. Zucker; Neda Jahanshad; Joseph A. King; Paul M. Thompson; Laura A. Berner; Stefan Ehrlich

doi:10.1016/j.biopsych.2022.04.022

Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group

Esther Walton, Fabio Bernardoni, Victoria Luise Batury, Klaas Bahnsen, Sara Larivière, Giovanni Abbate-Daga, Susana Andres-Perpiña, Lasse Bang, Amanda Bischoff-Grethe, Samantha J. Brooks, Iain C. Campbell, Giammarco Cascino, Josefina Castro-Fornieles, Enrico Collantoni, Federico D'Agata, Brigitte Dahmen, Unna N. Danner, Angela Favaro, Jamie D. Feusner, Guido K.W. FrankHans Christoph Friederich, John L. Graner, Beate Herpertz-Dahlmann, Andreas Hess, Stefanie Horndasch, Allan S. Kaplan, Lisa Katrin Kaufmann, Walter H. Kaye, Sahib S. Khalsa, Kevin S. LaBar, Luca Lavagnino, Luisa Lazaro, Renzo Manara, Amy E. Miles, Gabriella F. Milos, Alessio Maria Monteleone, Palmiero Monteleone, Benson Mwangi, Owen O'Daly, Jose Pariente, Julie Roesch, Ulrike H. Schmidt, Jochen Seitz, Megan E. Shott, Joe J. Simon, Paul A.M. Smeets, Christian K. Tamnes, Elena Tenconi, Sophia I. Thomopoulos, Annemarie A. van Elburg, Aristotle N. Voineskos, Georg G. von Polier, Christina E. Wierenga, Nancy L. Zucker, Neda Jahanshad, Joseph A. King, Paul M. Thompson, Laura A. Berner, Stefan Ehrlich^*

^*Corresponding author for this work

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

44 Citations (Scopus)

Abstract

Background: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. Methods: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). Results: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. Conclusions: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.

Original language	English
Pages (from-to)	730-738
Number of pages	9
Journal	Biological psychiatry
Volume	92
Issue number	9
DOIs	https://doi.org/10.1016/j.biopsych.2022.04.022
Publication status	Published - 1 Nov 2022

Keywords

BMI
Cortical thickness
MRI
Subcortical volume
Surface area

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.biopsych.2022.04.022

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Walton, E., Bernardoni, F., Batury, V. L., Bahnsen, K., Larivière, S., Abbate-Daga, G., Andres-Perpiña, S., Bang, L., Bischoff-Grethe, A., Brooks, S. J., Campbell, I. C., Cascino, G., Castro-Fornieles, J., Collantoni, E., D'Agata, F., Dahmen, B., Danner, U. N., Favaro, A., Feusner, J. D., ... Ehrlich, S. (2022). Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group. Biological psychiatry, 92(9), 730-738. https://doi.org/10.1016/j.biopsych.2022.04.022

@article{8b41dafd837d4979a203508d2bf233ff,

title = "Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group",

abstract = "Background: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. Methods: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). Results: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. Conclusions: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.",

keywords = "BMI, Cortical thickness, MRI, Subcortical volume, Surface area",

author = "Esther Walton and Fabio Bernardoni and Batury, {Victoria Luise} and Klaas Bahnsen and Sara Larivi{\`e}re and Giovanni Abbate-Daga and Susana Andres-Perpi{\~n}a and Lasse Bang and Amanda Bischoff-Grethe and Brooks, {Samantha J.} and Campbell, {Iain C.} and Giammarco Cascino and Josefina Castro-Fornieles and Enrico Collantoni and Federico D'Agata and Brigitte Dahmen and Danner, {Unna N.} and Angela Favaro and Feusner, {Jamie D.} and Frank, {Guido K.W.} and Friederich, {Hans Christoph} and Graner, {John L.} and Beate Herpertz-Dahlmann and Andreas Hess and Stefanie Horndasch and Kaplan, {Allan S.} and Kaufmann, {Lisa Katrin} and Kaye, {Walter H.} and Khalsa, {Sahib S.} and LaBar, {Kevin S.} and Luca Lavagnino and Luisa Lazaro and Renzo Manara and Miles, {Amy E.} and Milos, {Gabriella F.} and Monteleone, {Alessio Maria} and Palmiero Monteleone and Benson Mwangi and Owen O'Daly and Jose Pariente and Julie Roesch and Schmidt, {Ulrike H.} and Jochen Seitz and Shott, {Megan E.} and Simon, {Joe J.} and Smeets, {Paul A.M.} and Tamnes, {Christian K.} and Elena Tenconi and Thomopoulos, {Sophia I.} and {van Elburg}, {Annemarie A.} and Voineskos, {Aristotle N.} and {von Polier}, {Georg G.} and Wierenga, {Christina E.} and Zucker, {Nancy L.} and Neda Jahanshad and King, {Joseph A.} and Thompson, {Paul M.} and Berner, {Laura A.} and Stefan Ehrlich",

note = "Funding Information: This work was supported by the Carus Promotionskolleg (to KB), Ministerio de Igualdad (Grant No. 234/09 [to SA-P]), Generalitat de Catalunya (Grant No. 2009 SGR 1119 [to SA-P and LLaz] and Grant No. 2017 SGR 4881 [to JC-F]), National Institutes of Health (Grant No. R21MH86017 [to AB-G and CEW], Grant No. R01MH113588 [to AB-G, WHK, and CEW], Grant No. RC1MH088678 [to JLG, KSL, NLZ, and JAK], and Grant No. R01MH042984-17A1 [to WHK]), Biomedical Research Centre (to ICC), Alicia Koplowitz Foundation (Grant No. DN040546 [to JC-F]), German Ministry for Education and Research (Grant Nos. 01GV0602 and 01GV0623 [to BD, BH-D, JSS, and GGvP]), National Institute of Mental Health (Grant Nos. R01MH105662 and R01MH093535 [to JDF], Grant Nos. K23MH080135 and R01MH096777 [to GKWF and MES], Grant No. K23MH112949 [to SSK], and Grant No. K23MH118418 [to LAB]), Centre for Addiction and Mental Health Alternative Funding Plan Innovation Fund (to ASK, AEM, and ANV), Swiss Anorexia Nervosa Foundation (Project No. 19-12 [to L-KK and GFM] and Project No. 57-16 [to JJS] and to SE), Palatin Foundation (to L-KK and GFM), Gottfried and Julia Bangerter-Rhyner-Foundation (to L-KK and GFM), Weston A. Price Foundation (to WHK), Carlos III Research Institute of the Spanish Ministry of Health (Grant No. FIS PI040829 [to LLaz]), National Institute for Health Research Mental Health Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King's College London (ICC, OO, and UHS), German Research Foundation (Grant Nos. SI 2087/2-1 and BR 4852/1-1 [to JJS] and Grant Nos. EH 367/5-1 and EH 367/7-1 [to SE]), Research Council of Norway (Grant Nos. 288083 and 223273 [to CKT]), South-Eastern Norway Regional Health Authority (Grant Nos. 2019069, 2021070, and 500189 [to CKT]), National Institute of Health Research Senior Investigator Award (to UHS), NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (to LAB), and Technische Universit{\"a}t Dresden SFB 940 (to SE). This work was further supported by the European Union Horizon 2020 EarlyCause project (Grant No. 848158 [to EW]). The ENIGMA Working Group acknowledges the National Institutes of Health Big Data to Knowledge award for foundational support and consortium development (Grant No. U54 EB020403 [to PMT]). All data produced in the present study are available upon reasonable request to the authors. The authors report no biomedical financial interests or potential conflicts of interest. Funding Information: This work was supported by the Carus Promotionskolleg (to KB), Ministerio de Igualdad (Grant No. 234/09 [to SA-P]), Generalitat de Catalunya (Grant No. 2009 SGR 1119 [to SA-P and LLaz] and Grant No. 2017 SGR 4881 [to JC-F]), National Institutes of Health (Grant No. R21MH86017 [to AB-G and CEW], Grant No. R01MH113588 [to AB-G, WHK, and CEW], Grant No. RC1MH088678 [to JLG, KSL, NLZ, and JAK], and Grant No. R01MH042984-17A1 [to WHK]), Biomedical Research Centre (to ICC), Alicia Koplowitz Foundation (Grant No. DN040546 [to JC-F]), German Ministry for Education and Research (Grant Nos. 01GV0602 and 01GV0623 [to BD, BH-D, JSS, and GGvP]), National Institute of Mental Health (Grant Nos. R01MH105662 and R01MH093535 [to JDF], Grant Nos. K23MH080135 and R01MH096777 [to GKWF and MES], Grant No. K23MH112949 [to SSK], and Grant No. K23MH118418 [to LAB]), Centre for Addiction and Mental Health Alternative Funding Plan Innovation Fund (to ASK, AEM, and ANV), Swiss Anorexia Nervosa Foundation (Project No. 19-12 [to L-KK and GFM] and Project No. 57-16 [to JJS] and to SE), Palatin Foundation (to L-KK and GFM), Gottfried and Julia Bangerter-Rhyner-Foundation (to L-KK and GFM), Weston A. Price Foundation (to WHK), Carlos III Research Institute of the Spanish Ministry of Health (Grant No. FIS PI040829 [to LLaz]), National Institute for Health Research Mental Health Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London (ICC, OO, and UHS), German Research Foundation (Grant Nos. SI 2087/2-1 and BR 4852/1-1 [to JJS] and Grant Nos. EH 367/5-1 and EH 367/7-1 [to SE]), Research Council of Norway (Grant Nos. 288083 and 223273 [to CKT]), South-Eastern Norway Regional Health Authority (Grant Nos. 2019069 , 2021070 , and 500189 [to CKT]), National Institute of Health Research Senior Investigator Award (to UHS), NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (to LAB), and Technische Universit{\"a}t Dresden SFB 940 (to SE). This work was further supported by the European Union Horizon 2020 EarlyCause project (Grant No. 848158 [to EW]). Funding Information: The ENIGMA Working Group acknowledges the National Institutes of Health Big Data to Knowledge award for foundational support and consortium development (Grant No. U54 EB020403 [to PMT]). Publisher Copyright: {\textcopyright} 2022 Society of Biological Psychiatry",

year = "2022",

month = nov,

day = "1",

doi = "10.1016/j.biopsych.2022.04.022",

language = "English",

volume = "92",

pages = "730--738",

journal = "Biological psychiatry",

issn = "0006-3223",

publisher = "Elsevier",

number = "9",

}

Walton, E, Bernardoni, F, Batury, VL, Bahnsen, K, Larivière, S, Abbate-Daga, G, Andres-Perpiña, S, Bang, L, Bischoff-Grethe, A, Brooks, SJ, Campbell, IC, Cascino, G, Castro-Fornieles, J, Collantoni, E, D'Agata, F, Dahmen, B, Danner, UN, Favaro, A, Feusner, JD, Frank, GKW, Friederich, HC, Graner, JL, Herpertz-Dahlmann, B, Hess, A, Horndasch, S, Kaplan, AS, Kaufmann, LK, Kaye, WH, Khalsa, SS, LaBar, KS, Lavagnino, L, Lazaro, L, Manara, R, Miles, AE, Milos, GF, Monteleone, AM, Monteleone, P, Mwangi, B, O'Daly, O, Pariente, J, Roesch, J, Schmidt, UH, Seitz, J, Shott, ME, Simon, JJ, Smeets, PAM, Tamnes, CK, Tenconi, E, Thomopoulos, SI, van Elburg, AA, Voineskos, AN, von Polier, GG, Wierenga, CE, Zucker, NL, Jahanshad, N, King, JA, Thompson, PM, Berner, LA & Ehrlich, S 2022, 'Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group', Biological psychiatry, vol. 92, no. 9, pp. 730-738. https://doi.org/10.1016/j.biopsych.2022.04.022

Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group. / Walton, Esther; Bernardoni, Fabio; Batury, Victoria Luise et al.
In: Biological psychiatry, Vol. 92, No. 9, 01.11.2022, p. 730-738.

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

TY - JOUR

T1 - Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa

T2 - A Coordinated Analysis by the ENIGMA Eating Disorders Working Group

AU - Walton, Esther

AU - Bernardoni, Fabio

AU - Batury, Victoria Luise

AU - Bahnsen, Klaas

AU - Larivière, Sara

AU - Abbate-Daga, Giovanni

AU - Andres-Perpiña, Susana

AU - Bang, Lasse

AU - Bischoff-Grethe, Amanda

AU - Brooks, Samantha J.

AU - Campbell, Iain C.

AU - Cascino, Giammarco

AU - Castro-Fornieles, Josefina

AU - Collantoni, Enrico

AU - D'Agata, Federico

AU - Dahmen, Brigitte

AU - Danner, Unna N.

AU - Favaro, Angela

AU - Feusner, Jamie D.

AU - Frank, Guido K.W.

AU - Friederich, Hans Christoph

AU - Graner, John L.

AU - Herpertz-Dahlmann, Beate

AU - Hess, Andreas

AU - Horndasch, Stefanie

AU - Kaplan, Allan S.

AU - Kaufmann, Lisa Katrin

AU - Kaye, Walter H.

AU - Khalsa, Sahib S.

AU - LaBar, Kevin S.

AU - Lavagnino, Luca

AU - Lazaro, Luisa

AU - Manara, Renzo

AU - Miles, Amy E.

AU - Milos, Gabriella F.

AU - Monteleone, Alessio Maria

AU - Monteleone, Palmiero

AU - Mwangi, Benson

AU - O'Daly, Owen

AU - Pariente, Jose

AU - Roesch, Julie

AU - Schmidt, Ulrike H.

AU - Seitz, Jochen

AU - Shott, Megan E.

AU - Simon, Joe J.

AU - Smeets, Paul A.M.

AU - Tamnes, Christian K.

AU - Tenconi, Elena

AU - Thomopoulos, Sophia I.

AU - van Elburg, Annemarie A.

AU - Voineskos, Aristotle N.

AU - von Polier, Georg G.

AU - Wierenga, Christina E.

AU - Zucker, Nancy L.

AU - Jahanshad, Neda

AU - King, Joseph A.

AU - Thompson, Paul M.

AU - Berner, Laura A.

AU - Ehrlich, Stefan

N1 - Funding Information: This work was supported by the Carus Promotionskolleg (to KB), Ministerio de Igualdad (Grant No. 234/09 [to SA-P]), Generalitat de Catalunya (Grant No. 2009 SGR 1119 [to SA-P and LLaz] and Grant No. 2017 SGR 4881 [to JC-F]), National Institutes of Health (Grant No. R21MH86017 [to AB-G and CEW], Grant No. R01MH113588 [to AB-G, WHK, and CEW], Grant No. RC1MH088678 [to JLG, KSL, NLZ, and JAK], and Grant No. R01MH042984-17A1 [to WHK]), Biomedical Research Centre (to ICC), Alicia Koplowitz Foundation (Grant No. DN040546 [to JC-F]), German Ministry for Education and Research (Grant Nos. 01GV0602 and 01GV0623 [to BD, BH-D, JSS, and GGvP]), National Institute of Mental Health (Grant Nos. R01MH105662 and R01MH093535 [to JDF], Grant Nos. K23MH080135 and R01MH096777 [to GKWF and MES], Grant No. K23MH112949 [to SSK], and Grant No. K23MH118418 [to LAB]), Centre for Addiction and Mental Health Alternative Funding Plan Innovation Fund (to ASK, AEM, and ANV), Swiss Anorexia Nervosa Foundation (Project No. 19-12 [to L-KK and GFM] and Project No. 57-16 [to JJS] and to SE), Palatin Foundation (to L-KK and GFM), Gottfried and Julia Bangerter-Rhyner-Foundation (to L-KK and GFM), Weston A. Price Foundation (to WHK), Carlos III Research Institute of the Spanish Ministry of Health (Grant No. FIS PI040829 [to LLaz]), National Institute for Health Research Mental Health Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King's College London (ICC, OO, and UHS), German Research Foundation (Grant Nos. SI 2087/2-1 and BR 4852/1-1 [to JJS] and Grant Nos. EH 367/5-1 and EH 367/7-1 [to SE]), Research Council of Norway (Grant Nos. 288083 and 223273 [to CKT]), South-Eastern Norway Regional Health Authority (Grant Nos. 2019069, 2021070, and 500189 [to CKT]), National Institute of Health Research Senior Investigator Award (to UHS), NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (to LAB), and Technische Universität Dresden SFB 940 (to SE). This work was further supported by the European Union Horizon 2020 EarlyCause project (Grant No. 848158 [to EW]). The ENIGMA Working Group acknowledges the National Institutes of Health Big Data to Knowledge award for foundational support and consortium development (Grant No. U54 EB020403 [to PMT]). All data produced in the present study are available upon reasonable request to the authors. The authors report no biomedical financial interests or potential conflicts of interest. Funding Information: This work was supported by the Carus Promotionskolleg (to KB), Ministerio de Igualdad (Grant No. 234/09 [to SA-P]), Generalitat de Catalunya (Grant No. 2009 SGR 1119 [to SA-P and LLaz] and Grant No. 2017 SGR 4881 [to JC-F]), National Institutes of Health (Grant No. R21MH86017 [to AB-G and CEW], Grant No. R01MH113588 [to AB-G, WHK, and CEW], Grant No. RC1MH088678 [to JLG, KSL, NLZ, and JAK], and Grant No. R01MH042984-17A1 [to WHK]), Biomedical Research Centre (to ICC), Alicia Koplowitz Foundation (Grant No. DN040546 [to JC-F]), German Ministry for Education and Research (Grant Nos. 01GV0602 and 01GV0623 [to BD, BH-D, JSS, and GGvP]), National Institute of Mental Health (Grant Nos. R01MH105662 and R01MH093535 [to JDF], Grant Nos. K23MH080135 and R01MH096777 [to GKWF and MES], Grant No. K23MH112949 [to SSK], and Grant No. K23MH118418 [to LAB]), Centre for Addiction and Mental Health Alternative Funding Plan Innovation Fund (to ASK, AEM, and ANV), Swiss Anorexia Nervosa Foundation (Project No. 19-12 [to L-KK and GFM] and Project No. 57-16 [to JJS] and to SE), Palatin Foundation (to L-KK and GFM), Gottfried and Julia Bangerter-Rhyner-Foundation (to L-KK and GFM), Weston A. Price Foundation (to WHK), Carlos III Research Institute of the Spanish Ministry of Health (Grant No. FIS PI040829 [to LLaz]), National Institute for Health Research Mental Health Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King’s College London (ICC, OO, and UHS), German Research Foundation (Grant Nos. SI 2087/2-1 and BR 4852/1-1 [to JJS] and Grant Nos. EH 367/5-1 and EH 367/7-1 [to SE]), Research Council of Norway (Grant Nos. 288083 and 223273 [to CKT]), South-Eastern Norway Regional Health Authority (Grant Nos. 2019069 , 2021070 , and 500189 [to CKT]), National Institute of Health Research Senior Investigator Award (to UHS), NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (to LAB), and Technische Universität Dresden SFB 940 (to SE). This work was further supported by the European Union Horizon 2020 EarlyCause project (Grant No. 848158 [to EW]). Funding Information: The ENIGMA Working Group acknowledges the National Institutes of Health Big Data to Knowledge award for foundational support and consortium development (Grant No. U54 EB020403 [to PMT]). Publisher Copyright: © 2022 Society of Biological Psychiatry

PY - 2022/11/1

Y1 - 2022/11/1

N2 - Background: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. Methods: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). Results: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. Conclusions: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.

AB - Background: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. Methods: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). Results: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. Conclusions: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.

KW - BMI

KW - Cortical thickness

KW - MRI

KW - Subcortical volume

KW - Surface area

UR - http://www.scopus.com/inward/record.url?scp=85136665057&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2022.04.022

DO - 10.1016/j.biopsych.2022.04.022

M3 - Article

AN - SCOPUS:85136665057

SN - 0006-3223

VL - 92

SP - 730

EP - 738

JO - Biological psychiatry

JF - Biological psychiatry

IS - 9

ER -

Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group

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Keywords

UN SDGs

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