Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders : Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group

Nils Opel; Anbupalam Thalamuthu; Yuri Milaneschi; Dominik Grotegerd; Claas Flint; Ramona Leenings; Janik Goltermann; Maike Richter; Tim Hahn; Georg Woditsch; Klaus Berger; Marco Hermesdorf; Andrew McIntosh; Heather C Whalley; Mathew A Harris; Frank P MacMaster; Henrik Walter; Ilya M Veer; Thomas Frodl; Angela Carballedo; Axel Krug; Igor Nenadic; Tilo Kircher; Andre Aleman; Nynke A Groenewold; Dan J Stein; Jair C Soares; Giovana B Zunta-Soares; Benson Mwangi; Mon-Ju Wu; Martin Walter; Meng Li; Ben J Harrison; Christopher G Davey; Kathryn R Cullen; Bonnie Klimes-Dougan; Bryon A Mueller; Philipp G Sämann; Brenda Penninx; Laura Nawijn; Dick J Veltman; Lyubomir Aftanas; Ivan V Brak; Elena A Filimonova; Evgeniy A Osipov; Liesbeth Reneman; Anouk Schrantee; Hans J Grabe; Sandra Van der Auwera; Katharina Wittfeld; Norbert Hosten; Henry Völzke; Kang Sim; Ian H Gotlib; Matthew D Sacchet; Jim Lagopoulos; Sean N Hatton; Ian Hickie; Elena Pozzi; Paul M Thompson; Neda Jahanshad; Lianne Schmaal; Bernhard T Baune; Udo Dannlowski

doi:10.1038/s41380-020-0774-9

Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders : Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group

Nils Opel^*, Anbupalam Thalamuthu, Yuri Milaneschi, Dominik Grotegerd, Claas Flint, Ramona Leenings, Janik Goltermann, Maike Richter, Tim Hahn, Georg Woditsch, Klaus Berger, Marco Hermesdorf, Andrew McIntosh, Heather C Whalley, Mathew A Harris, Frank P MacMaster, Henrik Walter, Ilya M Veer, Thomas Frodl, Angela CarballedoAxel Krug, Igor Nenadic, Tilo Kircher, Andre Aleman, Nynke A Groenewold, Dan J Stein, Jair C Soares, Giovana B Zunta-Soares, Benson Mwangi, Mon-Ju Wu, Martin Walter, Meng Li, Ben J Harrison, Christopher G Davey, Kathryn R Cullen, Bonnie Klimes-Dougan, Bryon A Mueller, Philipp G Sämann, Brenda Penninx, Laura Nawijn, Dick J Veltman, Lyubomir Aftanas, Ivan V Brak, Elena A Filimonova, Evgeniy A Osipov, Liesbeth Reneman, Anouk Schrantee, Hans J Grabe, Sandra Van der Auwera, Katharina Wittfeld, Norbert Hosten, Henry Völzke, Kang Sim, Ian H Gotlib, Matthew D Sacchet, Jim Lagopoulos, Sean N Hatton, Ian Hickie, Elena Pozzi, Paul M Thompson, Neda Jahanshad, Lianne Schmaal, Bernhard T Baune, Udo Dannlowski

^*Corresponding author for this work

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

15 Citations (Scopus)

Abstract

Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = -0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.

Original language	English
Number of pages	14
Journal	Molecular Psychiatry
DOIs	https://doi.org/10.1038/s41380-020-0774-9
Publication status	E-pub ahead of print - 2020

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Brain structural abnormalities in obesity_ relation to age, genetic risk, and common psychiatric disordersFinal publisher's version, 2.75 MBLicence: Taverne

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Opel, N., Thalamuthu, A., Milaneschi, Y., Grotegerd, D., Flint, C., Leenings, R., Goltermann, J., Richter, M., Hahn, T., Woditsch, G., Berger, K., Hermesdorf, M., McIntosh, A., Whalley, H. C., Harris, M. A., MacMaster, F. P., Walter, H., Veer, I. M., Frodl, T., ... Dannlowski, U. (2020). Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders : Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group. Molecular Psychiatry. https://doi.org/10.1038/s41380-020-0774-9

Opel, Nils ; Thalamuthu, Anbupalam ; Milaneschi, Yuri ; Grotegerd, Dominik ; Flint, Claas ; Leenings, Ramona ; Goltermann, Janik ; Richter, Maike ; Hahn, Tim ; Woditsch, Georg ; Berger, Klaus ; Hermesdorf, Marco ; McIntosh, Andrew ; Whalley, Heather C ; Harris, Mathew A ; MacMaster, Frank P ; Walter, Henrik ; Veer, Ilya M ; Frodl, Thomas ; Carballedo, Angela ; Krug, Axel ; Nenadic, Igor ; Kircher, Tilo ; Aleman, Andre ; Groenewold, Nynke A ; Stein, Dan J ; Soares, Jair C ; Zunta-Soares, Giovana B ; Mwangi, Benson ; Wu, Mon-Ju ; Walter, Martin ; Li, Meng ; Harrison, Ben J ; Davey, Christopher G ; Cullen, Kathryn R ; Klimes-Dougan, Bonnie ; Mueller, Bryon A ; Sämann, Philipp G ; Penninx, Brenda ; Nawijn, Laura ; Veltman, Dick J ; Aftanas, Lyubomir ; Brak, Ivan V ; Filimonova, Elena A ; Osipov, Evgeniy A ; Reneman, Liesbeth ; Schrantee, Anouk ; Grabe, Hans J ; Van der Auwera, Sandra ; Wittfeld, Katharina ; Hosten, Norbert ; Völzke, Henry ; Sim, Kang ; Gotlib, Ian H ; Sacchet, Matthew D ; Lagopoulos, Jim ; Hatton, Sean N ; Hickie, Ian ; Pozzi, Elena ; Thompson, Paul M ; Jahanshad, Neda ; Schmaal, Lianne ; Baune, Bernhard T ; Dannlowski, Udo. / Brain structural abnormalities in obesity : relation to age, genetic risk, and common psychiatric disorders : Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group. In: Molecular Psychiatry. 2020.

@article{19c066178b054e1cb133b14e7c6102cc,

title = "Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders : Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group",

abstract = "Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = -0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.",

author = "Nils Opel and Anbupalam Thalamuthu and Yuri Milaneschi and Dominik Grotegerd and Claas Flint and Ramona Leenings and Janik Goltermann and Maike Richter and Tim Hahn and Georg Woditsch and Klaus Berger and Marco Hermesdorf and Andrew McIntosh and Whalley, {Heather C} and Harris, {Mathew A} and MacMaster, {Frank P} and Henrik Walter and Veer, {Ilya M} and Thomas Frodl and Angela Carballedo and Axel Krug and Igor Nenadic and Tilo Kircher and Andre Aleman and Groenewold, {Nynke A} and Stein, {Dan J} and Soares, {Jair C} and Zunta-Soares, {Giovana B} and Benson Mwangi and Mon-Ju Wu and Martin Walter and Meng Li and Harrison, {Ben J} and Davey, {Christopher G} and Cullen, {Kathryn R} and Bonnie Klimes-Dougan and Mueller, {Bryon A} and S{\"a}mann, {Philipp G} and Brenda Penninx and Laura Nawijn and Veltman, {Dick J} and Lyubomir Aftanas and Brak, {Ivan V} and Filimonova, {Elena A} and Osipov, {Evgeniy A} and Liesbeth Reneman and Anouk Schrantee and Grabe, {Hans J} and {Van der Auwera}, Sandra and Katharina Wittfeld and Norbert Hosten and Henry V{\"o}lzke and Kang Sim and Gotlib, {Ian H} and Sacchet, {Matthew D} and Jim Lagopoulos and Hatton, {Sean N} and Ian Hickie and Elena Pozzi and Thompson, {Paul M} and Neda Jahanshad and Lianne Schmaal and Baune, {Bernhard T} and Udo Dannlowski",

year = "2020",

doi = "10.1038/s41380-020-0774-9",

language = "English",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Nature Publishing Group",

}

Opel, N, Thalamuthu, A, Milaneschi, Y, Grotegerd, D, Flint, C, Leenings, R, Goltermann, J, Richter, M, Hahn, T, Woditsch, G, Berger, K, Hermesdorf, M, McIntosh, A, Whalley, HC, Harris, MA, MacMaster, FP, Walter, H, Veer, IM, Frodl, T, Carballedo, A, Krug, A, Nenadic, I, Kircher, T, Aleman, A, Groenewold, NA, Stein, DJ, Soares, JC, Zunta-Soares, GB, Mwangi, B, Wu, M-J, Walter, M, Li, M, Harrison, BJ, Davey, CG, Cullen, KR, Klimes-Dougan, B, Mueller, BA, Sämann, PG, Penninx, B, Nawijn, L, Veltman, DJ, Aftanas, L, Brak, IV, Filimonova, EA, Osipov, EA, Reneman, L, Schrantee, A, Grabe, HJ, Van der Auwera, S, Wittfeld, K, Hosten, N, Völzke, H, Sim, K, Gotlib, IH, Sacchet, MD, Lagopoulos, J, Hatton, SN, Hickie, I, Pozzi, E, Thompson, PM, Jahanshad, N, Schmaal, L, Baune, BT & Dannlowski, U 2020, 'Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders : Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group', Molecular Psychiatry. https://doi.org/10.1038/s41380-020-0774-9

Brain structural abnormalities in obesity : relation to age, genetic risk, and common psychiatric disorders : Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group. / Opel, Nils; Thalamuthu, Anbupalam; Milaneschi, Yuri; Grotegerd, Dominik; Flint, Claas; Leenings, Ramona; Goltermann, Janik; Richter, Maike; Hahn, Tim; Woditsch, Georg; Berger, Klaus; Hermesdorf, Marco; McIntosh, Andrew; Whalley, Heather C; Harris, Mathew A; MacMaster, Frank P; Walter, Henrik; Veer, Ilya M; Frodl, Thomas; Carballedo, Angela; Krug, Axel; Nenadic, Igor; Kircher, Tilo; Aleman, Andre; Groenewold, Nynke A; Stein, Dan J; Soares, Jair C; Zunta-Soares, Giovana B; Mwangi, Benson; Wu, Mon-Ju; Walter, Martin; Li, Meng; Harrison, Ben J; Davey, Christopher G; Cullen, Kathryn R; Klimes-Dougan, Bonnie; Mueller, Bryon A; Sämann, Philipp G; Penninx, Brenda; Nawijn, Laura; Veltman, Dick J; Aftanas, Lyubomir; Brak, Ivan V; Filimonova, Elena A; Osipov, Evgeniy A; Reneman, Liesbeth; Schrantee, Anouk; Grabe, Hans J; Van der Auwera, Sandra; Wittfeld, Katharina; Hosten, Norbert; Völzke, Henry; Sim, Kang; Gotlib, Ian H; Sacchet, Matthew D; Lagopoulos, Jim; Hatton, Sean N; Hickie, Ian; Pozzi, Elena; Thompson, Paul M; Jahanshad, Neda; Schmaal, Lianne; Baune, Bernhard T; Dannlowski, Udo.

In: Molecular Psychiatry, 2020.

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

TY - JOUR

T1 - Brain structural abnormalities in obesity

T2 - relation to age, genetic risk, and common psychiatric disorders : Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group

AU - Opel, Nils

AU - Thalamuthu, Anbupalam

AU - Milaneschi, Yuri

AU - Grotegerd, Dominik

AU - Flint, Claas

AU - Leenings, Ramona

AU - Goltermann, Janik

AU - Richter, Maike

AU - Hahn, Tim

AU - Woditsch, Georg

AU - Berger, Klaus

AU - Hermesdorf, Marco

AU - McIntosh, Andrew

AU - Whalley, Heather C

AU - Harris, Mathew A

AU - MacMaster, Frank P

AU - Walter, Henrik

AU - Veer, Ilya M

AU - Frodl, Thomas

AU - Carballedo, Angela

AU - Krug, Axel

AU - Nenadic, Igor

AU - Kircher, Tilo

AU - Aleman, Andre

AU - Groenewold, Nynke A

AU - Stein, Dan J

AU - Soares, Jair C

AU - Zunta-Soares, Giovana B

AU - Mwangi, Benson

AU - Wu, Mon-Ju

AU - Walter, Martin

AU - Li, Meng

AU - Harrison, Ben J

AU - Davey, Christopher G

AU - Cullen, Kathryn R

AU - Klimes-Dougan, Bonnie

AU - Mueller, Bryon A

AU - Sämann, Philipp G

AU - Penninx, Brenda

AU - Nawijn, Laura

AU - Veltman, Dick J

AU - Aftanas, Lyubomir

AU - Brak, Ivan V

AU - Filimonova, Elena A

AU - Osipov, Evgeniy A

AU - Reneman, Liesbeth

AU - Schrantee, Anouk

AU - Grabe, Hans J

AU - Van der Auwera, Sandra

AU - Wittfeld, Katharina

AU - Hosten, Norbert

AU - Völzke, Henry

AU - Sim, Kang

AU - Gotlib, Ian H

AU - Sacchet, Matthew D

AU - Lagopoulos, Jim

AU - Hatton, Sean N

AU - Hickie, Ian

AU - Pozzi, Elena

AU - Thompson, Paul M

AU - Jahanshad, Neda

AU - Schmaal, Lianne

AU - Baune, Bernhard T

AU - Dannlowski, Udo

PY - 2020

Y1 - 2020

N2 - Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = -0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.

AB - Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = -0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.

U2 - 10.1038/s41380-020-0774-9

DO - 10.1038/s41380-020-0774-9

M3 - Article

C2 - 32467648

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

ER -

Opel N, Thalamuthu A, Milaneschi Y, Grotegerd D, Flint C, Leenings R et al. Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders : Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group. Molecular Psychiatry. 2020. https://doi.org/10.1038/s41380-020-0774-9