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

Author:

Antoniades Mathilde1ORCID,Fu Cynthia2ORCID,Erus Guray1,Garcia Jose1,Fan Yong1,Arnone Danilo3,Arnott Stephen4,Chen Taolin5,Choi Ki Sueng6,Fatt Cherise Chin7,Frey Benicio8,Frokjaer Vibe9,Ganz Melanie9,Godlewska Beata10,Hassel Stefanie11,Ho Keith12,McIntosh Andrew13ORCID,Qin Kun5,Rotzinger Susan12,Sacchet Matthew14,Savitz Jonathan15ORCID,Shou Haochang1,Singh Ashish1ORCID,Stolicyn Aleks16ORCID,Strigo Irina17,Strother Stephen18,Tosun Duygu17,Victor Teresa15,Wei Dongtao19,Wise Toby20,Zahn Roland20,Anderson Ian21,Deakin J.F. William21,Dunlop Boadie22,Elliott Rebecca21,Gong Qiyong23ORCID,Gotlib Ian24,Harmer Catherine10,Kennedy Sidney12,Knudsen Gitte9,Mayberg Helen25,Paulus Martin26ORCID,Qiu Jiang19,Trivedi Madhukar7,Whalley Heather16,Yan Chao-Gan27,Young Allan3,Davatzikos Christos1

Affiliation:

1. University of Pennsylvania

2. University of East London

3. King’s College London

4. Rotman Research Institute

5. Sichuan University

6. Icahn School of Medicine at Mount Sinai

7. University of Texas Southwestern Medical Center

8. McMaster University

9. University of Copenhagen

10. University of Oxford

11. University of Calgary

12. University Health Network

13. The University of Edinburgh

14. Harvard Medical School

15. Laureate Institute for Brain Research

16. University of Edinburgh

17. University of California San Francisco

18. Department of Medical Biophysics

19. Southwest University

20. King's College London

21. University of Manchester

22. Emory University School of Medicine

23. West China Hospital of Sichuan University

24. Stanford University

25. The Nash Family Center for Advanced Circuit Therapeutics

26. Laureate Institute for Brain Research, Tulsa, USA

27. Institute of Psychology

Abstract

Abstract Importance: Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Identifying neuroimaging-based biomarkers might aid in defining the disease-related dimensions that characterize MDD and predict treatment response. Objective: To investigate the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressant or placebo. Design: Big data consortium (COORDINATE-MDD) sharing raw MRI data in first episode and recurrent MDD, deep clinical phenotyping, and state-of-the art machine learning analysis, involving harmonization of multi-center MRI data and the application of semi-supervised machine learning clustering, HYDRA, to regional brain volumes. Setting: International, multi-center, community-based MDD and healthy controls. Participants: International sample (N=1384), consisting of medication-free, first episode and recurrent MDD individuals (N=685) in a current depressive episode of moderate to severe intensity, that is not treatment resistant depression, and healthy controls (N=699). Prospective longitudinal treatment response data were available in a subset of MDD individuals (N=359 MDD). Treatments were SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Treatment duration was 6-8 weeks, and symptom severity was measured by clinician-rated scales. Main outcomes: First episode and recurrent MDD is optimally characterized by two neuroanatomical dimensions, which show distinct treatment effects to placebo and SSRI antidepressant medications. Results: Dimension 1 is characterized by preserved gray and white matter (N=290 MDD), whereas Dimension 2 is characterized by widespread subtle reductions in gray and white matter (N=395 MDD) relative to healthy controls. There are no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, but there is a significant dimension by treatment response interaction effect. Dimension 1 shows a significant decrease in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%), whereas Dimension 2 shows a comparable improvement to either SSRI (46.9%) or placebo (42.2%) (β=-18.3, 95% CI (-0.34 to -0.2), p=0.03). Conclusions and Relevance: Neuroimaging-based markers may aid in characterizing the MDD dimensions that predict treatment response. In an iterative process, we can characterize the disease-based dimensions that comprise MDD.

Publisher

Research Square Platform LLC

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