Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo

Cynthia H. Y. Fu; Mathilde Antoniades; Guray Erus; Jose a. Garcia; Yong Fan; Danilo Arnone; Stephen r. Arnott; Taolin Chen; Ki sueng Choi; Cherise chin Fatt; Benicio n. Frey; Vibe g. Frokjaer; Melanie Ganz; Beata r. Godlewska; Stefanie Hassel; Keith Ho; Andrew m. Mcintosh; Kun Qin; Susan Rotzinger; Matthew d. Sacchet; Jonathan Savitz; Haochang Shou; Ashish Singh; Aleks Stolicyn; Irina Strigo; Stephen c. Strother; Duygu Tosun; Teresa a. Victor; Dongtao Wei; Toby Wise; Roland Zahn; Ian m. Anderson; W. edward Craighead; J. f. william Deakin; Boadie w. Dunlop; Rebecca Elliott; Qiyong Gong; Ian h. Gotlib; Catherine j. Harmer; Sidney h. Kennedy; Gitte m. Knudsen; Helen s. Mayberg; Martin p. Paulus; Jiang Qiu; Madhukar h. Trivedi; Heather c. Whalley; Chao-Gan Yan; Allan H. Young; Christos Davatzikos

doi:10.1038/s44220-023-00187-w

Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo

Cynthia H. Y. Fu, Mathilde Antoniades, Guray Erus, Jose a. Garcia, Yong Fan, Danilo Arnone, Stephen r. Arnott, Taolin Chen, Ki sueng Choi, Cherise chin Fatt, Benicio n. Frey, Vibe g. Frokjaer, Melanie Ganz, Beata r. Godlewska, Stefanie Hassel, Keith Ho, Andrew m. Mcintosh, Kun Qin, Susan Rotzinger, Matthew d. SacchetJonathan Savitz, Haochang Shou, Ashish Singh, Aleks Stolicyn, Irina Strigo, Stephen c. Strother, Duygu Tosun, Teresa a. Victor, Dongtao Wei, Toby Wise, Roland Zahn, Ian m. Anderson, W. edward Craighead, J. f. william Deakin, Boadie w. Dunlop, Rebecca Elliott, Qiyong Gong, Ian h. Gotlib, Catherine j. Harmer, Sidney h. Kennedy, Gitte m. Knudsen, Helen s. Mayberg, Martin p. Paulus, Jiang Qiu, Madhukar h. Trivedi, Heather c. Whalley, Chao-Gan Yan, Allan H. Young, Christos Davatzikos

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

Abstract

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples ( N = 1,384) of medication-free individuals with first-episode and recurrent MDD ( N = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls ( N = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals ( N = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter ( N = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter ( N = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) ( β = -18.3, 95% CI (-34.3 to -2.3), P = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.

Original language	English
Pages (from-to)	164-176
Number of pages	13
Journal	Nature Mental Health
Volume	2
Issue number	2
Early online date	12 Jan 2024
DOIs	https://doi.org/10.1038/s44220-023-00187-w https://doi.org/10.1038/s44220-023-00187-w
Publication status	Published - Feb 2024

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Fu, C. H. Y., Antoniades, M., Erus, G., Garcia, J. A., Fan, Y., Arnone, D., Arnott, S. R., Chen, T., Choi, K. S., Fatt, C. C., Frey, B. N., Frokjaer, V. G., Ganz, M., Godlewska, B. R., Hassel, S., Ho, K., Mcintosh, A. M., Qin, K., Rotzinger, S., ... Davatzikos, C. (2024). Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo. Nature Mental Health , 2(2), 164-176. https://doi.org/10.1038/s44220-023-00187-w, https://doi.org/10.1038/s44220-023-00187-w

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title = "Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo",

abstract = "Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples ( N = 1,384) of medication-free individuals with first-episode and recurrent MDD ( N = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls ( N = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals ( N = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter ( N = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter ( N = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) ( β = -18.3, 95% CI (-34.3 to -2.3), P = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response. ",

author = "Fu, {Cynthia H. Y.} and Mathilde Antoniades and Guray Erus and Garcia, {Jose a.} and Yong Fan and Danilo Arnone and Arnott, {Stephen r.} and Taolin Chen and Choi, {Ki sueng} and Fatt, {Cherise chin} and Frey, {Benicio n.} and Frokjaer, {Vibe g.} and Melanie Ganz and Godlewska, {Beata r.} and Stefanie Hassel and Keith Ho and Mcintosh, {Andrew m.} and Kun Qin and Susan Rotzinger and Sacchet, {Matthew d.} and Jonathan Savitz and Haochang Shou and Ashish Singh and Aleks Stolicyn and Irina Strigo and Strother, {Stephen c.} and Duygu Tosun and Victor, {Teresa a.} and Dongtao Wei and Toby Wise and Roland Zahn and Anderson, {Ian m.} and Craighead, {W. edward} and Deakin, {J. f. william} and Dunlop, {Boadie w.} and Rebecca Elliott and Qiyong Gong and Gotlib, {Ian h.} and Harmer, {Catherine j.} and Kennedy, {Sidney h.} and Knudsen, {Gitte m.} and Mayberg, {Helen s.} and Paulus, {Martin p.} and Jiang Qiu and Trivedi, {Madhukar h.} and Whalley, {Heather c.} and Chao-Gan Yan and Young, {Allan H.} and Christos Davatzikos",

note = "{\textcopyright} The Author(s) 2024.",

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month = feb,

doi = "10.1038/s44220-023-00187-w",

language = "English",

volume = "2",

pages = "164--176",

journal = "Nature Mental Health ",

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Fu, CHY, Antoniades, M, Erus, G, Garcia, JA, Fan, Y, Arnone, D, Arnott, SR, Chen, T, Choi, KS, Fatt, CC, Frey, BN, Frokjaer, VG, Ganz, M, Godlewska, BR, Hassel, S, Ho, K, Mcintosh, AM, Qin, K, Rotzinger, S, Sacchet, MD, Savitz, J, Shou, H, Singh, A, Stolicyn, A, Strigo, I, Strother, SC, Tosun, D, Victor, TA, Wei, D, Wise, T , Zahn, R, Anderson, IM, Craighead, WE, Deakin, JFW, Dunlop, BW, Elliott, R, Gong, Q, Gotlib, IH, Harmer, CJ, Kennedy, SH, Knudsen, GM, Mayberg, HS, Paulus, MP, Qiu, J, Trivedi, MH, Whalley, HC, Yan, C-G, Young, AH & Davatzikos, C 2024, 'Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo', Nature Mental Health , vol. 2, no. 2, pp. 164-176. https://doi.org/10.1038/s44220-023-00187-w, https://doi.org/10.1038/s44220-023-00187-w

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T1 - Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo

AU - Fu, Cynthia H. Y.

AU - Antoniades, Mathilde

AU - Erus, Guray

AU - Garcia, Jose a.

AU - Fan, Yong

AU - Arnone, Danilo

AU - Arnott, Stephen r.

AU - Chen, Taolin

AU - Choi, Ki sueng

AU - Fatt, Cherise chin

AU - Frey, Benicio n.

AU - Frokjaer, Vibe g.

AU - Ganz, Melanie

AU - Godlewska, Beata r.

AU - Hassel, Stefanie

AU - Ho, Keith

AU - Mcintosh, Andrew m.

AU - Qin, Kun

AU - Rotzinger, Susan

AU - Sacchet, Matthew d.

AU - Savitz, Jonathan

AU - Shou, Haochang

AU - Singh, Ashish

AU - Stolicyn, Aleks

AU - Strigo, Irina

AU - Strother, Stephen c.

AU - Tosun, Duygu

AU - Victor, Teresa a.

AU - Wei, Dongtao

AU - Wise, Toby

AU - Zahn, Roland

AU - Anderson, Ian m.

AU - Craighead, W. edward

AU - Deakin, J. f. william

AU - Dunlop, Boadie w.

AU - Elliott, Rebecca

AU - Gong, Qiyong

AU - Gotlib, Ian h.

AU - Harmer, Catherine j.

AU - Kennedy, Sidney h.

AU - Knudsen, Gitte m.

AU - Mayberg, Helen s.

AU - Paulus, Martin p.

AU - Qiu, Jiang

AU - Trivedi, Madhukar h.

AU - Whalley, Heather c.

AU - Yan, Chao-Gan

AU - Young, Allan H.

AU - Davatzikos, Christos

PY - 2024/2

Y1 - 2024/2

N2 - Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples ( N = 1,384) of medication-free individuals with first-episode and recurrent MDD ( N = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls ( N = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals ( N = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter ( N = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter ( N = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) ( β = -18.3, 95% CI (-34.3 to -2.3), P = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.

AB - Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples ( N = 1,384) of medication-free individuals with first-episode and recurrent MDD ( N = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls ( N = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals ( N = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter ( N = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter ( N = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) ( β = -18.3, 95% CI (-34.3 to -2.3), P = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.

U2 - 10.1038/s44220-023-00187-w

DO - 10.1038/s44220-023-00187-w

M3 - Article

C2 - 38948238

SN - 2731-6076

VL - 2

SP - 164

EP - 176

JO - Nature Mental Health

JF - Nature Mental Health

IS - 2

ER -

Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo

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