Brain Aging in Major Depressive Disorder: Results from the ENIGMA Major Depressive Disorder working group

Laura KM Han, Richard Dinga, Tim Hahn, Christopher Ching, Lisa Eyler, Lyubomir Aftanas, Moji Aghajani, Andre Aleman, Bernhard Baune, Klaus Berger, Ivan Brak, Geraldo Busatto Filho, Angela Carballedo, Colm Connolly, Baptiste Couvy-Duchesne, Kathryn Cullen, Udo Dannlowski, Christopher Davey, Danai Dima, Fabio Duran & 126 others Verena Enneking, Elena Filimonova, Stefan Frenzel, Thomas Frodl, Cynthia Fu, Beata Godlewska, Ian Gotlib, Hans Grabe, Nynke Groenewold, Dominik Grotegerd, Oliver Gruber, Geoffrey Hall, Ben Harrison, Sean Hatton, Marco Hermesdorf, Ian Hickie, Tiffany Ho, Norbert Hosten, Andreas Jansen, Claas Kahler, Tilo Kircher, Bonnie Klimes-Dougan, Bernd Kramer, Axel Krug, Jim Lagopoulos, Ramona Leenings, Frank MacMaster, Glenda MacQueen, Andrew McIntosh, Quinn McLellan, Katie McMahon, Sarah Medland, Bryon Mueller, Benson Mwangi, Evgeny Osipov, Maria Portella, Elena Pozzi, Liesbeth Reneman, Jonathan Repple, Pedro Rosa, Matthew Sacchet, Philipp Saemann, Knut Schnell, Anouk Schrantee, Egle Simulionyte, Jair Soares, Jens Sommer, Dan Stein, Olaf Steinstrater, Lachlan Strike, Sophia Thomopoulos, Marie-Jose van Tol, Ilya Veer, Robert Vermeiren, Henrik Walter, Nic van der Wee, Steven van der Werff, Heather Whalley, Nils Winter, Katharina Wittfeld, Margaret Wright, Mon-Ju Wu, Henry Volzke, Tony Yang, Vasileios Zannias, Greig de Zubicaray, Goavana Zunta-Soares, Christoph Abe, Martin Alda, Ole Andreassen, Erlend Boen, Caterina Bonnin, Erick Canales-Rodriguez, Dara Cannon, Xavier Caseras, Tiffany Chaim-Avancini, Tobjorn Elvsashagen, Pauline Favre, Sonya Foley, Janice Fullerton, Jose Goikolea, Bartholomeus Haarman, Thomas Hajek, Chantal Henry, Josselin Houenou, Fleur Howells, Martin Ingvar, Rayus Kuplicki, Beny Lafer, Mikael Landen, Rodrigo Machado-Vieira, Ulrik Malt, Colm McDonald, Philip Mitchell, Leila Nabulsi, Maria Otaduy, Bronwyn Overs, Mircea Polosan, Edith Pomarol-Clotet, Joaquim Radua, Maria Rive, Gloria Roberts, Henricus Ruhe, Raymond Salvador, Salvador Sarro, Theodore Satterthwaite, Jonathan Savitz, Aart Schene, Peter Schofield, Mauricio Serpa, Kang Sim, Marcio Soeiro-de-Souza, Ashley Sutherland, Henk Temmingh, Garrett Timmons, Anne Uhlmann, Eduard Vieta, Daniel Wolf, Marcus Zanetti, Neda Jahanshad, Paul Thompson, Dick Veltman, Brenda Penninx, Andre Marquand, James Cole, Lianne Schmaal

Research output: Contribution to journalArticleAcademic

Abstract

Background: Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in MDD patients, and whether this process is associated with clinical characteristics in a large multi-center international dataset. Methods: We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 29 samples worldwide. Normative brain aging was estimated by predicting chronological age (10-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 1,147 male and 1,386 female controls from the ENIGMA MDD working group. The learned model parameters were applied to 1,089 male controls and 1,167 depressed males, and 1,326 female controls and 2,044 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted brain age and chronological age was calculated to indicate brain predicted age difference (brain-PAD). Findings: On average, MDD patients showed a higher brain-PAD of +0.90 (SE 0.21) years (Cohen's d=0.12, 95% CI 0.06-0.17) compared to controls. Relative to controls, first-episode and currently depressed patients showed higher brain-PAD (+1.2 [0.3] years), and the largest effect was observed in those with late-onset depression (+1.7 [0.7] years). In addition, higher brain-PAD was associated with higher self-reported depressive symptomatology (b=0.05, p=0.004). Interpretation: This highly powered collaborative effort showed subtle patterns of abnormal structural brain aging in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the predictive value of these brain-PAD estimates.
Original languageEnglish
Pages (from-to)560623
JournalBiorxiv
DOIs
Publication statusPublished - 2019

Cite this

Han, Laura KM ; Dinga, Richard ; Hahn, Tim ; Ching, Christopher ; Eyler, Lisa ; Aftanas, Lyubomir ; Aghajani, Moji ; Aleman, Andre ; Baune, Bernhard ; Berger, Klaus ; Brak, Ivan ; Filho, Geraldo Busatto ; Carballedo, Angela ; Connolly, Colm ; Couvy-Duchesne, Baptiste ; Cullen, Kathryn ; Dannlowski, Udo ; Davey, Christopher ; Dima, Danai ; Duran, Fabio ; Enneking, Verena ; Filimonova, Elena ; Frenzel, Stefan ; Frodl, Thomas ; Fu, Cynthia ; Godlewska, Beata ; Gotlib, Ian ; Grabe, Hans ; Groenewold, Nynke ; Grotegerd, Dominik ; Gruber, Oliver ; Hall, Geoffrey ; Harrison, Ben ; Hatton, Sean ; Hermesdorf, Marco ; Hickie, Ian ; Ho, Tiffany ; Hosten, Norbert ; Jansen, Andreas ; Kahler, Claas ; Kircher, Tilo ; Klimes-Dougan, Bonnie ; Kramer, Bernd ; Krug, Axel ; Lagopoulos, Jim ; Leenings, Ramona ; MacMaster, Frank ; MacQueen, Glenda ; McIntosh, Andrew ; McLellan, Quinn ; McMahon, Katie ; Medland, Sarah ; Mueller, Bryon ; Mwangi, Benson ; Osipov, Evgeny ; Portella, Maria ; Pozzi, Elena ; Reneman, Liesbeth ; Repple, Jonathan ; Rosa, Pedro ; Sacchet, Matthew ; Saemann, Philipp ; Schnell, Knut ; Schrantee, Anouk ; Simulionyte, Egle ; Soares, Jair ; Sommer, Jens ; Stein, Dan ; Steinstrater, Olaf ; Strike, Lachlan ; Thomopoulos, Sophia ; Tol, Marie-Jose van ; Veer, Ilya ; Vermeiren, Robert ; Walter, Henrik ; Wee, Nic van der ; Werff, Steven van der ; Whalley, Heather ; Winter, Nils ; Wittfeld, Katharina ; Wright, Margaret ; Wu, Mon-Ju ; Volzke, Henry ; Yang, Tony ; Zannias, Vasileios ; Zubicaray, Greig de ; Zunta-Soares, Goavana ; Abe, Christoph ; Alda, Martin ; Andreassen, Ole ; Boen, Erlend ; Bonnin, Caterina ; Canales-Rodriguez, Erick ; Cannon, Dara ; Caseras, Xavier ; Chaim-Avancini, Tiffany ; Elvsashagen, Tobjorn ; Favre, Pauline ; Foley, Sonya ; Fullerton, Janice ; Goikolea, Jose ; Haarman, Bartholomeus ; Hajek, Thomas ; Henry, Chantal ; Houenou, Josselin ; Howells, Fleur ; Ingvar, Martin ; Kuplicki, Rayus ; Lafer, Beny ; Landen, Mikael ; Machado-Vieira, Rodrigo ; Malt, Ulrik ; McDonald, Colm ; Mitchell, Philip ; Nabulsi, Leila ; Otaduy, Maria ; Overs, Bronwyn ; Polosan, Mircea ; Pomarol-Clotet, Edith ; Radua, Joaquim ; Rive, Maria ; Roberts, Gloria ; Ruhe, Henricus ; Salvador, Raymond ; Sarro, Salvador ; Satterthwaite, Theodore ; Savitz, Jonathan ; Schene, Aart ; Schofield, Peter ; Serpa, Mauricio ; Sim, Kang ; Soeiro-de-Souza, Marcio ; Sutherland, Ashley ; Temmingh, Henk ; Timmons, Garrett ; Uhlmann, Anne ; Vieta, Eduard ; Wolf, Daniel ; Zanetti, Marcus ; Jahanshad, Neda ; Thompson, Paul ; Veltman, Dick ; Penninx, Brenda ; Marquand, Andre ; Cole, James ; Schmaal, Lianne. / Brain Aging in Major Depressive Disorder: Results from the ENIGMA Major Depressive Disorder working group. In: Biorxiv. 2019 ; pp. 560623.
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title = "Brain Aging in Major Depressive Disorder: Results from the ENIGMA Major Depressive Disorder working group",
abstract = "Background: Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in MDD patients, and whether this process is associated with clinical characteristics in a large multi-center international dataset. Methods: We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 29 samples worldwide. Normative brain aging was estimated by predicting chronological age (10-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 1,147 male and 1,386 female controls from the ENIGMA MDD working group. The learned model parameters were applied to 1,089 male controls and 1,167 depressed males, and 1,326 female controls and 2,044 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted brain age and chronological age was calculated to indicate brain predicted age difference (brain-PAD). Findings: On average, MDD patients showed a higher brain-PAD of +0.90 (SE 0.21) years (Cohen's d=0.12, 95{\%} CI 0.06-0.17) compared to controls. Relative to controls, first-episode and currently depressed patients showed higher brain-PAD (+1.2 [0.3] years), and the largest effect was observed in those with late-onset depression (+1.7 [0.7] years). In addition, higher brain-PAD was associated with higher self-reported depressive symptomatology (b=0.05, p=0.004). Interpretation: This highly powered collaborative effort showed subtle patterns of abnormal structural brain aging in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the predictive value of these brain-PAD estimates.",
author = "Han, {Laura KM} and Richard Dinga and Tim Hahn and Christopher Ching and Lisa Eyler and Lyubomir Aftanas and Moji Aghajani and Andre Aleman and Bernhard Baune and Klaus Berger and Ivan Brak and Filho, {Geraldo Busatto} and Angela Carballedo and Colm Connolly and Baptiste Couvy-Duchesne and Kathryn Cullen and Udo Dannlowski and Christopher Davey and Danai Dima and Fabio Duran and Verena Enneking and Elena Filimonova and Stefan Frenzel and Thomas Frodl and Cynthia Fu and Beata Godlewska and Ian Gotlib and Hans Grabe and Nynke Groenewold and Dominik Grotegerd and Oliver Gruber and Geoffrey Hall and Ben Harrison and Sean Hatton and Marco Hermesdorf and Ian Hickie and Tiffany Ho and Norbert Hosten and Andreas Jansen and Claas Kahler and Tilo Kircher and Bonnie Klimes-Dougan and Bernd Kramer and Axel Krug and Jim Lagopoulos and Ramona Leenings and Frank MacMaster and Glenda MacQueen and Andrew McIntosh and Quinn McLellan and Katie McMahon and Sarah Medland and Bryon Mueller and Benson Mwangi and Evgeny Osipov and Maria Portella and Elena Pozzi and Liesbeth Reneman and Jonathan Repple and Pedro Rosa and Matthew Sacchet and Philipp Saemann and Knut Schnell and Anouk Schrantee and Egle Simulionyte and Jair Soares and Jens Sommer and Dan Stein and Olaf Steinstrater and Lachlan Strike and Sophia Thomopoulos and Tol, {Marie-Jose van} and Ilya Veer and Robert Vermeiren and Henrik Walter and Wee, {Nic van der} and Werff, {Steven van der} and Heather Whalley and Nils Winter and Katharina Wittfeld and Margaret Wright and Mon-Ju Wu and Henry Volzke and Tony Yang and Vasileios Zannias and Zubicaray, {Greig de} and Goavana Zunta-Soares and Christoph Abe and Martin Alda and Ole Andreassen and Erlend Boen and Caterina Bonnin and Erick Canales-Rodriguez and Dara Cannon and Xavier Caseras and Tiffany Chaim-Avancini and Tobjorn Elvsashagen and Pauline Favre and Sonya Foley and Janice Fullerton and Jose Goikolea and Bartholomeus Haarman and Thomas Hajek and Chantal Henry and Josselin Houenou and Fleur Howells and Martin Ingvar and Rayus Kuplicki and Beny Lafer and Mikael Landen and Rodrigo Machado-Vieira and Ulrik Malt and Colm McDonald and Philip Mitchell and Leila Nabulsi and Maria Otaduy and Bronwyn Overs and Mircea Polosan and Edith Pomarol-Clotet and Joaquim Radua and Maria Rive and Gloria Roberts and Henricus Ruhe and Raymond Salvador and Salvador Sarro and Theodore Satterthwaite and Jonathan Savitz and Aart Schene and Peter Schofield and Mauricio Serpa and Kang Sim and Marcio Soeiro-de-Souza and Ashley Sutherland and Henk Temmingh and Garrett Timmons and Anne Uhlmann and Eduard Vieta and Daniel Wolf and Marcus Zanetti and Neda Jahanshad and Paul Thompson and Dick Veltman and Brenda Penninx and Andre Marquand and James Cole and Lianne Schmaal",
year = "2019",
doi = "10.1101/560623",
language = "English",
pages = "560623",
journal = "Biorxiv",

}

Han, LKM, Dinga, R, Hahn, T, Ching, C, Eyler, L, Aftanas, L, Aghajani, M, Aleman, A, Baune, B, Berger, K, Brak, I, Filho, GB, Carballedo, A, Connolly, C, Couvy-Duchesne, B, Cullen, K, Dannlowski, U, Davey, C, Dima, D, Duran, F, Enneking, V, Filimonova, E, Frenzel, S, Frodl, T, Fu, C, Godlewska, B, Gotlib, I, Grabe, H, Groenewold, N, Grotegerd, D, Gruber, O, Hall, G, Harrison, B, Hatton, S, Hermesdorf, M, Hickie, I, Ho, T, Hosten, N, Jansen, A, Kahler, C, Kircher, T, Klimes-Dougan, B, Kramer, B, Krug, A, Lagopoulos, J, Leenings, R, MacMaster, F, MacQueen, G, McIntosh, A, McLellan, Q, McMahon, K, Medland, S, Mueller, B, Mwangi, B, Osipov, E, Portella, M, Pozzi, E, Reneman, L, Repple, J, Rosa, P, Sacchet, M, Saemann, P, Schnell, K, Schrantee, A, Simulionyte, E, Soares, J, Sommer, J, Stein, D, Steinstrater, O, Strike, L, Thomopoulos, S, Tol, M-JV, Veer, I, Vermeiren, R, Walter, H, Wee, NVD, Werff, SVD, Whalley, H, Winter, N, Wittfeld, K, Wright, M, Wu, M-J, Volzke, H, Yang, T, Zannias, V, Zubicaray, GD, Zunta-Soares, G, Abe, C, Alda, M, Andreassen, O, Boen, E, Bonnin, C, Canales-Rodriguez, E, Cannon, D, Caseras, X, Chaim-Avancini, T, Elvsashagen, T, Favre, P, Foley, S, Fullerton, J, Goikolea, J, Haarman, B, Hajek, T, Henry, C, Houenou, J, Howells, F, Ingvar, M, Kuplicki, R, Lafer, B, Landen, M, Machado-Vieira, R, Malt, U, McDonald, C, Mitchell, P, Nabulsi, L, Otaduy, M, Overs, B, Polosan, M, Pomarol-Clotet, E, Radua, J, Rive, M, Roberts, G, Ruhe, H, Salvador, R, Sarro, S, Satterthwaite, T, Savitz, J, Schene, A, Schofield, P, Serpa, M, Sim, K, Soeiro-de-Souza, M, Sutherland, A, Temmingh, H, Timmons, G, Uhlmann, A, Vieta, E, Wolf, D, Zanetti, M, Jahanshad, N, Thompson, P, Veltman, D, Penninx, B, Marquand, A, Cole, J & Schmaal, L 2019, 'Brain Aging in Major Depressive Disorder: Results from the ENIGMA Major Depressive Disorder working group' Biorxiv, pp. 560623. https://doi.org/10.1101/560623

Brain Aging in Major Depressive Disorder: Results from the ENIGMA Major Depressive Disorder working group. / Han, Laura KM; Dinga, Richard; Hahn, Tim; Ching, Christopher; Eyler, Lisa; Aftanas, Lyubomir; Aghajani, Moji; Aleman, Andre; Baune, Bernhard; Berger, Klaus; Brak, Ivan; Filho, Geraldo Busatto; Carballedo, Angela; Connolly, Colm; Couvy-Duchesne, Baptiste; Cullen, Kathryn; Dannlowski, Udo; Davey, Christopher; Dima, Danai; Duran, Fabio; Enneking, Verena; Filimonova, Elena; Frenzel, Stefan; Frodl, Thomas; Fu, Cynthia; Godlewska, Beata; Gotlib, Ian; Grabe, Hans; Groenewold, Nynke; Grotegerd, Dominik; Gruber, Oliver; Hall, Geoffrey; Harrison, Ben; Hatton, Sean; Hermesdorf, Marco; Hickie, Ian; Ho, Tiffany; Hosten, Norbert; Jansen, Andreas; Kahler, Claas; Kircher, Tilo; Klimes-Dougan, Bonnie; Kramer, Bernd; Krug, Axel; Lagopoulos, Jim; Leenings, Ramona; MacMaster, Frank; MacQueen, Glenda; McIntosh, Andrew; McLellan, Quinn; McMahon, Katie; Medland, Sarah; Mueller, Bryon; Mwangi, Benson; Osipov, Evgeny; Portella, Maria; Pozzi, Elena; Reneman, Liesbeth; Repple, Jonathan; Rosa, Pedro; Sacchet, Matthew; Saemann, Philipp; Schnell, Knut; Schrantee, Anouk; Simulionyte, Egle; Soares, Jair; Sommer, Jens; Stein, Dan; Steinstrater, Olaf; Strike, Lachlan; Thomopoulos, Sophia; Tol, Marie-Jose van; Veer, Ilya; Vermeiren, Robert; Walter, Henrik; Wee, Nic van der; Werff, Steven van der; Whalley, Heather; Winter, Nils; Wittfeld, Katharina; Wright, Margaret; Wu, Mon-Ju; Volzke, Henry; Yang, Tony; Zannias, Vasileios; Zubicaray, Greig de; Zunta-Soares, Goavana; Abe, Christoph; Alda, Martin; Andreassen, Ole; Boen, Erlend; Bonnin, Caterina; Canales-Rodriguez, Erick; Cannon, Dara; Caseras, Xavier; Chaim-Avancini, Tiffany; Elvsashagen, Tobjorn; Favre, Pauline; Foley, Sonya; Fullerton, Janice; Goikolea, Jose; Haarman, Bartholomeus; Hajek, Thomas; Henry, Chantal; Houenou, Josselin; Howells, Fleur; Ingvar, Martin; Kuplicki, Rayus; Lafer, Beny; Landen, Mikael; Machado-Vieira, Rodrigo; Malt, Ulrik; McDonald, Colm; Mitchell, Philip; Nabulsi, Leila; Otaduy, Maria; Overs, Bronwyn; Polosan, Mircea; Pomarol-Clotet, Edith; Radua, Joaquim; Rive, Maria; Roberts, Gloria; Ruhe, Henricus; Salvador, Raymond; Sarro, Salvador; Satterthwaite, Theodore; Savitz, Jonathan; Schene, Aart; Schofield, Peter; Serpa, Mauricio; Sim, Kang; Soeiro-de-Souza, Marcio; Sutherland, Ashley; Temmingh, Henk; Timmons, Garrett; Uhlmann, Anne; Vieta, Eduard; Wolf, Daniel; Zanetti, Marcus; Jahanshad, Neda; Thompson, Paul; Veltman, Dick; Penninx, Brenda; Marquand, Andre; Cole, James; Schmaal, Lianne.

In: Biorxiv, 2019, p. 560623.

Research output: Contribution to journalArticleAcademic

TY - JOUR

T1 - Brain Aging in Major Depressive Disorder: Results from the ENIGMA Major Depressive Disorder working group

AU - Han, Laura KM

AU - Dinga, Richard

AU - Hahn, Tim

AU - Ching, Christopher

AU - Eyler, Lisa

AU - Aftanas, Lyubomir

AU - Aghajani, Moji

AU - Aleman, Andre

AU - Baune, Bernhard

AU - Berger, Klaus

AU - Brak, Ivan

AU - Filho, Geraldo Busatto

AU - Carballedo, Angela

AU - Connolly, Colm

AU - Couvy-Duchesne, Baptiste

AU - Cullen, Kathryn

AU - Dannlowski, Udo

AU - Davey, Christopher

AU - Dima, Danai

AU - Duran, Fabio

AU - Enneking, Verena

AU - Filimonova, Elena

AU - Frenzel, Stefan

AU - Frodl, Thomas

AU - Fu, Cynthia

AU - Godlewska, Beata

AU - Gotlib, Ian

AU - Grabe, Hans

AU - Groenewold, Nynke

AU - Grotegerd, Dominik

AU - Gruber, Oliver

AU - Hall, Geoffrey

AU - Harrison, Ben

AU - Hatton, Sean

AU - Hermesdorf, Marco

AU - Hickie, Ian

AU - Ho, Tiffany

AU - Hosten, Norbert

AU - Jansen, Andreas

AU - Kahler, Claas

AU - Kircher, Tilo

AU - Klimes-Dougan, Bonnie

AU - Kramer, Bernd

AU - Krug, Axel

AU - Lagopoulos, Jim

AU - Leenings, Ramona

AU - MacMaster, Frank

AU - MacQueen, Glenda

AU - McIntosh, Andrew

AU - McLellan, Quinn

AU - McMahon, Katie

AU - Medland, Sarah

AU - Mueller, Bryon

AU - Mwangi, Benson

AU - Osipov, Evgeny

AU - Portella, Maria

AU - Pozzi, Elena

AU - Reneman, Liesbeth

AU - Repple, Jonathan

AU - Rosa, Pedro

AU - Sacchet, Matthew

AU - Saemann, Philipp

AU - Schnell, Knut

AU - Schrantee, Anouk

AU - Simulionyte, Egle

AU - Soares, Jair

AU - Sommer, Jens

AU - Stein, Dan

AU - Steinstrater, Olaf

AU - Strike, Lachlan

AU - Thomopoulos, Sophia

AU - Tol, Marie-Jose van

AU - Veer, Ilya

AU - Vermeiren, Robert

AU - Walter, Henrik

AU - Wee, Nic van der

AU - Werff, Steven van der

AU - Whalley, Heather

AU - Winter, Nils

AU - Wittfeld, Katharina

AU - Wright, Margaret

AU - Wu, Mon-Ju

AU - Volzke, Henry

AU - Yang, Tony

AU - Zannias, Vasileios

AU - Zubicaray, Greig de

AU - Zunta-Soares, Goavana

AU - Abe, Christoph

AU - Alda, Martin

AU - Andreassen, Ole

AU - Boen, Erlend

AU - Bonnin, Caterina

AU - Canales-Rodriguez, Erick

AU - Cannon, Dara

AU - Caseras, Xavier

AU - Chaim-Avancini, Tiffany

AU - Elvsashagen, Tobjorn

AU - Favre, Pauline

AU - Foley, Sonya

AU - Fullerton, Janice

AU - Goikolea, Jose

AU - Haarman, Bartholomeus

AU - Hajek, Thomas

AU - Henry, Chantal

AU - Houenou, Josselin

AU - Howells, Fleur

AU - Ingvar, Martin

AU - Kuplicki, Rayus

AU - Lafer, Beny

AU - Landen, Mikael

AU - Machado-Vieira, Rodrigo

AU - Malt, Ulrik

AU - McDonald, Colm

AU - Mitchell, Philip

AU - Nabulsi, Leila

AU - Otaduy, Maria

AU - Overs, Bronwyn

AU - Polosan, Mircea

AU - Pomarol-Clotet, Edith

AU - Radua, Joaquim

AU - Rive, Maria

AU - Roberts, Gloria

AU - Ruhe, Henricus

AU - Salvador, Raymond

AU - Sarro, Salvador

AU - Satterthwaite, Theodore

AU - Savitz, Jonathan

AU - Schene, Aart

AU - Schofield, Peter

AU - Serpa, Mauricio

AU - Sim, Kang

AU - Soeiro-de-Souza, Marcio

AU - Sutherland, Ashley

AU - Temmingh, Henk

AU - Timmons, Garrett

AU - Uhlmann, Anne

AU - Vieta, Eduard

AU - Wolf, Daniel

AU - Zanetti, Marcus

AU - Jahanshad, Neda

AU - Thompson, Paul

AU - Veltman, Dick

AU - Penninx, Brenda

AU - Marquand, Andre

AU - Cole, James

AU - Schmaal, Lianne

PY - 2019

Y1 - 2019

N2 - Background: Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in MDD patients, and whether this process is associated with clinical characteristics in a large multi-center international dataset. Methods: We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 29 samples worldwide. Normative brain aging was estimated by predicting chronological age (10-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 1,147 male and 1,386 female controls from the ENIGMA MDD working group. The learned model parameters were applied to 1,089 male controls and 1,167 depressed males, and 1,326 female controls and 2,044 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted brain age and chronological age was calculated to indicate brain predicted age difference (brain-PAD). Findings: On average, MDD patients showed a higher brain-PAD of +0.90 (SE 0.21) years (Cohen's d=0.12, 95% CI 0.06-0.17) compared to controls. Relative to controls, first-episode and currently depressed patients showed higher brain-PAD (+1.2 [0.3] years), and the largest effect was observed in those with late-onset depression (+1.7 [0.7] years). In addition, higher brain-PAD was associated with higher self-reported depressive symptomatology (b=0.05, p=0.004). Interpretation: This highly powered collaborative effort showed subtle patterns of abnormal structural brain aging in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the predictive value of these brain-PAD estimates.

AB - Background: Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in MDD patients, and whether this process is associated with clinical characteristics in a large multi-center international dataset. Methods: We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 29 samples worldwide. Normative brain aging was estimated by predicting chronological age (10-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 1,147 male and 1,386 female controls from the ENIGMA MDD working group. The learned model parameters were applied to 1,089 male controls and 1,167 depressed males, and 1,326 female controls and 2,044 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted brain age and chronological age was calculated to indicate brain predicted age difference (brain-PAD). Findings: On average, MDD patients showed a higher brain-PAD of +0.90 (SE 0.21) years (Cohen's d=0.12, 95% CI 0.06-0.17) compared to controls. Relative to controls, first-episode and currently depressed patients showed higher brain-PAD (+1.2 [0.3] years), and the largest effect was observed in those with late-onset depression (+1.7 [0.7] years). In addition, higher brain-PAD was associated with higher self-reported depressive symptomatology (b=0.05, p=0.004). Interpretation: This highly powered collaborative effort showed subtle patterns of abnormal structural brain aging in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the predictive value of these brain-PAD estimates.

UR - https://www.biorxiv.org/content/10.1101/560623v1

UR - http://www.mendeley.com/research/brain-aging-major-depressive-disorder-results-enigma-major-depressive-disorder-working-group

U2 - 10.1101/560623

DO - 10.1101/560623

M3 - Article

SP - 560623

JO - Biorxiv

JF - Biorxiv

ER -