Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo
Authors: Fu Cynthia H. Y. , Antoniades Mathilde , Erus Guray , Garcia Jose A. , Fan Yong , Arnone Danilo , Arnott Stephen R. , Chen Taolin , Choi Ki Sueng , Fatt Cherise Chin , Frey Benicio N. , Frokjaer Vibe G. , Ganz Melanie , Godlewska Beata R. , Hassel Stefanie , Ho Keith , McIntosh Andrew M. , Qin Kun , Rotzinger Susan , Sacchet Matthew D. , Savitz Jonathan , Shou Haochang , Singh Ashish , Stolicyn Aleks , Strigo Irina , Strother Stephen C. , Tosun Duygu , Victor Teresa A. , Wei Dongtao , Wise Toby , Zahn Roland , Anderson Ian M. , Craighead W. Edward , Deakin J. F. William , Dunlop Boadie W. , Elliott Rebecca , Gong Qiyong , Gotlib Ian H. , Harmer Catherine J. , Kennedy Sidney H. , Knudsen Gitte M. , Mayberg Helen S. , Paulus Martin P. , Qiu Jiang , Trivedi Madhukar H. , Whalley Heather C. , Yan Chao-Gan , Young Allan H. , Davatzikos Christos 
Published: January 2024

AbstractMajor 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.