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AJP CME: February 2020 - Effect of Intrinsic Patterns of Functional Brain Connectivity in Moderating Antidepressant Treatment Response in Major Depression

Activity Type:

  • Journal CME

Release Date: 2/1/2020

Expiration Date: 1/31/2022

  • AMA PRA Category 1: 1
  • Participation: 1



Objective: Major depressive disorder is associated with aberrant resting-state functional connectivity across multiple brain networks supporting emotion processing, executive function, and reward processing. The purpose of this study was to determine whether patterns of resting-state connectivity between brain regions predict differential outcome to antidepressant medication (sertraline) compared with placebo.

Methods: Participants in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study underwent structural and resting-state functional MRI at baseline. Participants were then randomly assigned to receive either sertraline or placebo treatment for 8 weeks (N=279). A region of interest–based approach was utilized to compute functional connectivity between brain regions. Linear mixed-model intent-to-treat analyses were used to identify brain regions that moderated (i.e., differentially predicted) outcomes between the sertraline and placebo arms.


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Educational Objective

The participant will categorize moderators of treatment response in brain regions affected by major depressive disorder.

Target Audience

This program is designed for all psychiatrists in clinical practice, residents in Graduate Medical Education programs, medical students interested in psychiatry, and other physicians who wish to advance their current knowledge of clinical medicine.

Estimated Time to Complete

Duration: 1 hour
Begin Date: February 1, 2020
End Date: January 31, 2022

How to Earn Credit

In order to earn CME credit, subscribers should read through the material presented in the article. After reading the article, complete the quiz and submit your evaluation and study hours (up to 1 AMA PRA Category 1 Credit™).  A score of 60% or higher is required to receive credit.


The American Psychiatric Association (APA) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

The APA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Faculty and Planner Disclosures

Title: Effect of Intrinsic Patterns of Functional Brain Connectivity in Moderating Antidepressant Treatment Response in Major Depression

Authors: Cherise R. Chin Fatt, Ph.D., Manish K. Jha, M.B.B.S., Crystal M. Cooper, Ph.D., Gregory Fonzo, Ph.D., Charles South, Ph.D., Bruce Grannemann, M.A., Thomas Carmody, Ph.D., Tracy L. Greer, Ph.D., Benji Kurian, M.D., Maurizio Fava, M.D., Patrick J. McGrath, M.D., Phillip Adams, Ph.D., Melvin McInnis, M.D., Ramin V. Parsey, M.D, Ph.D., Myrna Weissman, Ph.D., Mary L. Phillips, M.D., Amit Etkin, M.D., Ph.D., Madhukar H. Trivedi, M.D.

Affiliations: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (C.R.C.F., M.K.J., C.M.C., C.S., B.G., T.C., T.L.G., B.K., M.H.T.); Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York (M.K.J.); Department of Psychiatry and Behavioral Sciences and Stanford Neurosciences Institute, Stanford University, Stanford, Calif. (G.F., A.E.); Mental Illness Research, Education, and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif. (G.F., A.E.); Department of Psychiatry, Massachusetts General Hospital, Boston (M.F.); New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York (P.J.M.G., P.A., M.W.); Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor (M.M.I.); Department of Psychiatry and Behavioral Science and Department of Radiology, Stony Brook University, Stony Brook, N.Y. (R.V.P.); and Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh (M.L.P.).

Disclosures: Dr. Jha has received contract research support from Acadia Pharmaceuticals and Janssen Research. Dr. Greer has received research funding from NARSAD and contracted research support from Janssen Research and Development; she has received honoraria and/or consultant fees from Lundbeck and Takeda Pharmaceuticals International. Dr. Kurian has received grant support from Evotec, Forest Pharmaceuticals, Johnson & Johnson, Naurex, NIMH, Pfizer, Rexahn, and Targacept and is employed by Health Care Service Corporation. Dr. Fava has received research support from Abbott Laboratories, Alkermes, American Cyanamid, Aspect Medical Systems, AstraZeneca, Avanir Pharmaceuticals, BioResearch, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Clintara, Cerecor, Covance, Covidien, Eli Lilly, EnVivo Pharmaceuticals, Euthymics Bioscience, Forest Pharmaceuticals, Ganeden Biotech, GlaxoSmithKline, Harvard Clinical Research Institute, Hoffmann-LaRoche, Icon Clinical Research, i3 Innovus/Ingenix, Janssen R&D, Jed Foundation, Johnson & Johnson Pharmaceutical Research and Development, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Lundbeck, MedAvante, Methylation Sciences, NARSAD, National Center for Complementary and Alternative Medicine, Neuralstem, NIDA, NIMH, Novartis, Organon Pharmaceuticals, Pamlab, Pfizer, Pharmacia-Upjohn, Pharmaceutical Research Associates, Pharmavite, PharmoRx Therapeutics, Photothera, Reckitt Benckiser, Roche Pharmaceuticals, RCT Logic (formerly Clinical Trials Solutions), Sanofi-Aventis US, Shire, Solvay Pharmaceuticals, Stanley Medical Research Institute, Synthelabo, Tal Medical, and Wyeth-Ayerst Laboratories; he has served as adviser or consultant to Abbott Laboratories, Acadia, Affectis Pharmaceuticals, Alkermes, Amarin Pharma, Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Avanir Pharmaceuticals, AXSOME Therapeutics, Bayer, Best Practice Project Management, Biogen, BioMarin Pharmaceuticals, Biovail Corporation, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Cerecor, CNS Response, Compellis Pharmaceuticals, Cypress Pharmaceutical, DiagnoSearch Life Sciences, Dainippon Sumitomo Pharma, Dov Pharmaceuticals, Edgemont Pharmaceuticals, Eisai, Eli Lilly, EnVivo Pharmaceuticals, ePharmaSolutions, EPIX Pharmaceuticals, Euthymics Bioscience, Fabre-Kramer Pharmaceuticals, Forest Pharmaceuticals, Forum Pharmaceuticals, Genomind, GlaxoSmithKline, Grunenthal GmbH, i3 Innovus/Ingenis, Intracellular, Janssen Pharmaceutica, Jazz Pharmaceuticals, Johnson & Johnson Pharmaceutical Research and Development, Knoll Pharmaceuticals, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante, Merck, MSI Methylation Sciences, Naurex, Nestle Health Sciences, Neuralstem, Neuronetics, NextWave Pharmaceuticals, Novartis, Nutrition 21, Orexigen Therapeutics, Organon Pharmaceuticals, Osmotica, Otsuka Pharmaceuticals, Pamlab, Pfizer, PharmaStar, Pharmavite, PharmoRx Therapeutics, Precision Human Biolaboratory, Prexa Pharmaceuticals, Puretech Ventures, PsychoGenics, Psylin Neurosciences, RCT Logic (Formerly Clinical Trials Solutions), Rexahn Pharmaceuticals, Ridge Diagnostics, Roche, Sanofi-Aventis US, Sepracor, Servier Laboratories, Schering-Plough, Solvay Pharmaceuticals, Somaxon Pharmaceuticals, Somerset Pharmaceuticals, Sunovion Pharmaceuticals, Supernus Pharmaceuticals, Synthelabo, Taisho Pharmaceutical, Takeda Pharmaceutical Company, Tal Medical, Tetragenex Pharmaceuticals, TransForm Pharmaceuticals, Transcept Pharmaceuticals, Vanda Pharmaceuticals, and VistaGen; he has received speaking or publishing fees from Adamed, Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, AstraZeneca, Belvoir Media Group, Boehringer Ingelheim GmbH, Bristol-Myers Squibb, Cephalon, CME Institute/Physicians Postgraduate Press, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Imedex, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed Elsevier, Novartis, Organon Pharmaceuticals, Pfizer, PharmaStar, United BioSource, and Wyeth-Ayerst Laboratories; he has equity holdings in Compellis and PsyBrain; he has a patent for Sequential Parallel Comparison Design, licensed by Massachusetts General Hospital to Pharmaceutical Product Development, and a patent application for a combination of ketamine plus scopolamine in major depressive disorder, licensed by Massachusetts General Hospital to Biohaven; and he receives royalties for the MGH Cognitive and Physical Functioning Questionnaire, the Sexual Functioning Inventory, the Antidepressant Treatment Response Questionnaire, Discontinuation-Emergent Signs and Symptoms, the Symptoms of Depression Questionnaire, and SAFER, and from Lippincott, Williams & Wilkins, Wolkers Kluwer, and World Scientific Publishing. Dr. McGrath has received funding from the Forest Research Laboratories, Naurex Pharmaceuticals (now Allergan), the New York State Department of Mental Hygiene, NIMH, the Research Foundation for Mental Hygiene (New York State), and Sunovion Pharmaceuticals. Dr. McInnis has received research support from Janssen Pharmaceuticals; he has served as a consultant for Janssen Pharmaceuticals and Otsuka; and he is co-owner of Priori AI. Dr. Weissman has received funding from NARSAD, NIDA, NIMH, the Sackler Foundation, and the Templeton Foundation; and she receives royalties from American Psychiatric Association Press, MultiHealth Systems, Oxford University Press, and Perseus Press. Dr. Phillips has received funding from NIMH and an honorarium from Sunovion Pharmaceuticals. Dr. Etkin has received research funding from the Brain and Behavior Research Foundation, Brain Resource, Cohen Veterans Bioscience, Dana Foundation, the Department of Veterans Affairs, NIMH, and the Stanford Neurosciences Institute; he has served as a consultant for Acadia, Cervel, Janssen, Lundbeck, Otsuka, Posit Science, and Takeda; and he holds equity in Mindstrong Health and Akili Interactive. Dr. Trivedi has served as an adviser or consultant for Abbott Laboratories, Abdi Ibrahim, Akzo (Organon Pharmaceuticals), Alkermes, AstraZeneca, Axon Advisors, Bristol-Myers Squibb, Cephalon, Cerecor, CME Institute of Physicians, Concert Pharmaceuticals, Eli Lilly, Evotec, Fabre Kramer Pharmaceuticals, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Global Services, Janssen Pharmaceutica Products, Johnson & Johnson PRD, Libby, Lundbeck, Meade Johnson, MedAvante, Medtronic, Merck, Mitsubishi Tanabe Pharma Development America, Naurex, Neuronetics, Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals, Pfizer, PgxHealth, Phoenix Marketing Solutions, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche Products, Sepracor, Shire Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/Puretech Venture, Targacept, Transcept, VantagePoint, Vivus, and Wyeth-Ayerst Laboratories; he has received grants or research support from the Agency for Healthcare Research and Quality, Cyberonics, NARSAD, NIDA, and NIMH. The other authors report no financial relationships with commercial interests.

Discussion of unapproved or investigational use of products*: No.

 *APA policy requires disclosure by CME authors of unapproved or investigational use of products discussed in CME programs. Off-label use of medications by individual physicians is permitted and common. Decisions about off-label use can be guided by scientific literature and clinical experience.

 Program Planners

Ned H. Kalin, M.D. (Editor-in-Chief, AJP); Carolyn Rodriguez, M.D., Ph.D. (Deputy Editor, AJP); Michael D. Roy (Editorial Director, AJP); Michael A. Pogachar (Online Content Manager, Journals). Dr. Kalin has served as a consultant to the Board of Scientific Advisors, the Pritzker Neuropsychiatric Disorders Research Consortium, and the Skyland Trail Advisory Board and as Councilor, Society of Biological Psychiatry. Dr. Rodriguez has served as a consultant to Allergan, Blackthorn, Epiodyne, and Rugen. Mr. Roy and Mr. Pogachar report no financial relationships with commercial interests.

Hardware/Software Requirements

This internet-based CME activity is best experienced using Internet Explorer 8+, Mozilla Firefox 3+, Safari 4+. This Web site requires that JavaScript and session cookies be enabled. Certain activities may require additional software to view multimedia, presentation, or printable versions of the content. These activities will be marked as such and will provide links to the required software. That software may be: Adobe Flash, Adobe Acrobat, Microsoft PowerPoint, and Windows Media Player.

Optimal System Configuration:

  • Flash Player: Adobe Flash Player 10.1+ 
  • Browser: Firefox 3+, Internet Explorer 8.0+, Safari 4.0+, or Google Chrome 7.0+ 
  • Operating System: Windows XP+ or Mac OS X 10.4+ 
  • Internet Connection: 1 Mbps or higher
  • Screen Resolution: 1024 x 768 pixels.

Minimum Requirements:

  • Windows PC:500-MHz Pentium II; Windows XP or higher; 128 MB RAM; Video Card at least 64MB of video memory; Sound Card at least 16-bit; Macromedia Flash Player 10 or higher, audio playback with speakers for programs with video content; Firefox 1.1+, Internet Explorer 7.0+, Safari 1.0+, Google Chrome, or Opera
  • Macintosh: Mac OS X 10.3 or higher with latest updates installed; 1.83MHz Intel Core Duo or faster; RAM: 128MB or more; Video Card: at least 64MB of video memory; Sound Card: at least 16-bit

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