Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression

Summary

This study will examine multiple carefully selected clinical and biological markers, using both existing state-of-the-art technologies as well as pioneering, innovative approaches. The study is designed to identify moderators and mediators of treatment response for depression in order to specify a biosignature of treatment response for depression. Evaluation of the usefulness of these markers in a carefully conducted clinical trial comparing an antidepressant to placebo will assist in developing a Depression Treatment Response Index (DTRI) to help clinicians match treatments to patients with MDD, resulting in timely selection of treatments best suited for individual patients and thus approaching personalized treatment. The resulting index provides a truly novel means of synthesizing the contribution of key clinical and biological parameters in an easy to use tool for clinical care.

Timeline

Start

2011-07-29

Primary completion

2016-04

Completion

2016-04

Publications

• Background Chase HW, Fournier JC, Greenberg T, Almeida JR, Stiffler R, Zevallos CR, Aslam H, Cooper C, Deckersbach T, Weyandt S, Adams P, Toups M, Carmody T, Oquendo MA, Peltier S, Fava M, McGrath PJ, Weissman M, Parsey R, McInnis MG, Kurian B, Trivedi MH, Phillips ML. Accounting for Dynamic Fluctuations across Time when Examining fMRI Test-Retest Reliability: Analysis of a Reward Paradigm in the EMBARC Study. PLoS One. 2015 May 11;10(5):e0126326. doi: 10.1371/journal.pone.0126326. eCollection 2015.
• Background Fournier JC, Chase HW, Greenberg T, Etkin A, Almeida JR, Stiffler R, Deckersbach T, Weyandt S, Cooper C, Toups M, Carmody T, Kurian B, Peltier S, Adams P, McInnis MG, Oquendo MA, McGrath PJ, Fava M, Weissman M, Parsey R, Trivedi MH, Phillips ML. Neuroticism and Individual Differences in Neural Function in Unmedicated Major Depression: Findings from the EMBARC Study. Biol Psychiatry Cogn Neurosci Neuroimaging. 2017 Mar;2(2):138-148. doi: 10.1016/j.bpsc.2016.11.008. Epub 2016 Dec 6.
• Background Greenberg T, Chase HW, Almeida JR, Stiffler R, Zevallos CR, Aslam HA, Deckersbach T, Weyandt S, Cooper C, Toups M, Carmody T, Kurian B, Peltier S, Adams P, McInnis MG, Oquendo MA, McGrath PJ, Fava M, Weissman M, Parsey R, Trivedi MH, Phillips ML. Moderation of the Relationship Between Reward Expectancy and Prediction Error-Related Ventral Striatal Reactivity by Anhedonia in Unmedicated Major Depressive Disorder: Findings From the EMBARC Study. Am J Psychiatry. 2015 Sep 1;172(9):881-91. doi: 10.1176/appi.ajp.2015.14050594. Epub 2015 Jul 17.
• Background Petkova E, Ogden RT, Tarpey T, Ciarleglio A, Jiang B, Su Z, Carmody T, Adams P, Kraemer HC, Grannemann BD, Oquendo MA, Parsey R, Weissman M, McGrath PJ, Fava M, Trivedi MH. Statistical Analysis Plan for Stage 1 EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care) Study. Contemp Clin Trials Commun. 2017 Jun;6:22-30. doi: 10.1016/j.conctc.2017.02.007. Epub 2017 Feb 24.
• Background Pizzagalli DA, Webb CA, Dillon DG, Tenke CE, Kayser J, Goer F, Fava M, McGrath P, Weissman M, Parsey R, Adams P, Trombello J, Cooper C, Deldin P, Oquendo MA, McInnis MG, Carmody T, Bruder G, Trivedi MH. Pretreatment Rostral Anterior Cingulate Cortex Theta Activity in Relation to Symptom Improvement in Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Jun 1;75(6):547-554. doi: 10.1001/jamapsychiatry.2018.0252.
• Background Trivedi MH, South C, Jha MK, Rush AJ, Cao J, Kurian B, Phillips M, Pizzagalli DA, Trombello JM, Oquendo MA, Cooper C, Dillon DG, Webb C, Grannemann BD, Bruder G, McGrath PJ, Parsey R, Weissman M, Fava M. A Novel Strategy to Identify Placebo Responders: Prediction Index of Clinical and Biological Markers in the EMBARC Trial. Psychother Psychosom. 2018;87(5):285-295. doi: 10.1159/000491093. Epub 2018 Aug 15.
• Background Trivedi MH, McGrath PJ, Fava M, Parsey RV, Kurian BT, Phillips ML, Oquendo MA, Bruder G, Pizzagalli D, Toups M, Cooper C, Adams P, Weyandt S, Morris DW, Grannemann BD, Ogden RT, Buckner R, McInnis M, Kraemer HC, Petkova E, Carmody TJ, Weissman MM. Establishing moderators and biosignatures of antidepressant response in clinical care (EMBARC): Rationale and design. J Psychiatr Res. 2016 Jul;78:11-23. doi: 10.1016/j.jpsychires.2016.03.001. Epub 2016 Mar 15.
• Background Trombello JM, Pizzagalli DA, Weissman MM, Grannemann BD, Cooper CM, Greer TL, Malchow AL, Jha MK, Carmody TJ, Kurian BT, Webb CA, Dillon DG, McGrath PJ, Bruder G, Fava M, Parsey RV, McInnis MG, Adams P, Trivedi MH. Characterizing anxiety subtypes and the relationship to behavioral phenotyping in major depression: Results from the EMBARC study. J Psychiatr Res. 2018 Jul;102:207-215. doi: 10.1016/j.jpsychires.2018.04.003. Epub 2018 Apr 6.
• Background Ulke C, Tenke CE, Kayser J, Sander C, Bottger D, Wong LYX, Alvarenga JE, Fava M, McGrath PJ, Deldin PJ, Mcinnis MG, Trivedi MH, Weissman MM, Pizzagalli DA, Hegerl U, Bruder GE. Resting EEG Measures of Brain Arousal in a Multisite Study of Major Depression. Clin EEG Neurosci. 2019 Jan;50(1):3-12. doi: 10.1177/1550059418795578. Epub 2018 Sep 5.
• Background Webb CA, Trivedi MH, Cohen ZD, Dillon DG, Fournier JC, Goer F, Fava M, McGrath PJ, Weissman M, Parsey R, Adams P, Trombello JM, Cooper C, Deldin P, Oquendo MA, McInnis MG, Huys Q, Bruder G, Kurian BT, Jha M, DeRubeis RJ, Pizzagalli DA. Personalized prediction of antidepressant v. placebo response: evidence from the EMBARC study. Psychol Med. 2019 May;49(7):1118-1127. doi: 10.1017/S0033291718001708. Epub 2018 Jul 2.
• Tong X, Zhao K, Fonzo GA, Xie H, Carlisle NB, Keller CJ, Oathes DJ, Sheline Y, Nemeroff CB, Trivedi M, Etkin A, Zhang Y. Generalizable structure-function covariation predictive of antidepressant response revealed by target-oriented multimodal fusion. Nat Ment Health. 2026 Jan;4(1):85-101. doi: 10.1038/s44220-025-00541-0. Epub 2025 Dec 12.
• Dang Y, Lu B, Vanderwal T, Castellanos FX, Yan CG. Early-treatment cerebral blood flow change as a predictive biomarker of antidepressant treatment response: evidence from the EMBARC clinical trial. Psychol Med. 2024 Aug;54(11):3053-3062. doi: 10.1017/S0033291724001156. Epub 2024 May 9.
• Chin Fatt CR, Minhajuddin A, Jha MK, Mayes T, Rush AJ, Trivedi MH. Data driven clusters derived from resting state functional connectivity: Findings from the EMBARC study. J Psychiatr Res. 2023 Feb;158:150-156. doi: 10.1016/j.jpsychires.2022.12.002. Epub 2022 Dec 27.
• Jha MK, Schatzberg A, Minhajuddin A, Chin Fatt C, Mayes TL, Trivedi MH. Cross-Sectional Associations Among Symptoms of Pain, Irritability, and Depression and How These Symptoms Relate to Social Functioning and Quality of Life: Findings From the EMBARC and STRIDE Studies and the VitalSign6 Project. J Clin Psychiatry. 2021 Apr 13;82(3):20m13740. doi: 10.4088/JCP.20m13740.
• Jha MK, Fava M, Minhajuddin A, Chin Fatt C, Mischoulon D, Cusin C, Trivedi MH. Association of anger attacks with suicidal ideation in adults with major depressive disorder: Findings from the EMBARC study. Depress Anxiety. 2021 Jan;38(1):57-66. doi: 10.1002/da.23095. Epub 2020 Oct 10.
• Chin Fatt CR, Cooper C, Jha MK, Aslan S, Grannemann B, Kurian B, Greer TL, Fava M, Weissman M, McGrath PJ, Parsey RV, Etkin A, Phillips ML, Trivedi MH. Dorsolateral Prefrontal Cortex and Subcallosal Cingulate Connectivity Show Preferential Antidepressant Response in Major Depressive Disorder. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 Jan;6(1):20-28. doi: 10.1016/j.bpsc.2020.06.019. Epub 2020 Jul 8.
• Jha MK, Minhajuddin A, Chin Fatt C, Trivedi MH. Improvements in irritability with sertraline versus placebo: Findings from the EMBARC study. J Affect Disord. 2020 Oct 1;275:44-47. doi: 10.1016/j.jad.2020.06.021. Epub 2020 Jun 26.
• Rolle CE, Fonzo GA, Wu W, Toll R, Jha MK, Cooper C, Chin-Fatt C, Pizzagalli DA, Trombello JM, Deckersbach T, Fava M, Weissman MM, Trivedi MH, Etkin A. Cortical Connectivity Moderators of Antidepressant vs Placebo Treatment Response in Major Depressive Disorder: Secondary Analysis of a Randomized Clinical Trial. JAMA Psychiatry. 2020 Apr 1;77(4):397-408. doi: 10.1001/jamapsychiatry.2019.3867.
• Chin Fatt CR, Jha MK, Cooper CM, Fonzo G, South C, Grannemann B, Carmody T, Greer TL, Kurian B, Fava M, McGrath PJ, Adams P, McInnis M, Parsey RV, Weissman M, Phillips ML, Etkin A, Trivedi MH. Effect of Intrinsic Patterns of Functional Brain Connectivity in Moderating Antidepressant Treatment Response in Major Depression. Am J Psychiatry. 2020 Feb 1;177(2):143-154. doi: 10.1176/appi.ajp.2019.18070870. Epub 2019 Sep 20.
• Cooper CM, Chin Fatt CR, Jha M, Fonzo GA, Grannemann BD, Carmody T, Ali A, Aslan S, Almeida JRC, Deckersbach T, Fava M, Kurian BT, McGrath PJ, McInnis M, Parsey RV, Weissman M, Phillips ML, Lu H, Etkin A, Trivedi MH. Cerebral Blood Perfusion Predicts Response to Sertraline versus Placebo for Major Depressive Disorder in the EMBARC Trial. EClinicalMedicine. 2019 May 18;10:32-41. doi: 10.1016/j.eclinm.2019.04.007. eCollection 2019 Apr.
• Pillai RLI, Huang C, LaBella A, Zhang M, Yang J, Trivedi M, Weissman M, McGrath P, Fava M, Kurian B, Cooper C, McInnis M, Oquendo MA, Pizzagalli DA, Parsey RV, DeLorenzo C. Examining raphe-amygdala structural connectivity as a biological predictor of SSRI response. J Affect Disord. 2019 Sep 1;256:8-16. doi: 10.1016/j.jad.2019.05.055. Epub 2019 May 28.
• Whitton AE, Webb CA, Dillon DG, Kayser J, Rutherford A, Goer F, Fava M, McGrath P, Weissman M, Parsey R, Adams P, Trombello JM, Cooper C, Deldin P, Oquendo MA, McInnis MG, Carmody T, Bruder G, Trivedi MH, Pizzagalli DA. Pretreatment Rostral Anterior Cingulate Cortex Connectivity With Salience Network Predicts Depression Recovery: Findings From the EMBARC Randomized Clinical Trial. Biol Psychiatry. 2019 May 15;85(10):872-880. doi: 10.1016/j.biopsych.2018.12.007. Epub 2018 Dec 19.
• Liao A, Walker R, Carmody TJ, Cooper C, Shaw MA, Grannemann BD, Adams P, Bruder GE, McInnis MG, Webb CA, Dillon DG, Pizzagalli DA, Phillips ML, Kurian BT, Fava M, Parsey RV, McGrath PJ, Weissman MM, Trivedi MH. Anxiety and anhedonia in depression: Associations with neuroticism and cognitive control. J Affect Disord. 2019 Feb 15;245:1070-1078. doi: 10.1016/j.jad.2018.11.072. Epub 2018 Nov 14.

Drugs

Indications