Using fMRI connectivity to define a treatment-resistant form of post-traumatic stress disorder

Amit Etkin; Adi Maron-Katz; Wei Wu; Gregory A. Fonzo; Julia Huemer; Petra E. Vértes; Brian Patenaude; Jonas Richiardi; Madeleine S. Goodkind; Corey J. Keller; Jaime Ramos-Cejudo; Yevgeniya V. Zaiko; Kathy K. Peng; Emmanuel Shpigel; Parker Longwell; Russ T. Toll; Allison Thompson; Sanno Zack; Bryan Gonzalez; Raleigh Edelstein; Jingyun Chen; Irene Akingbade; Elizabeth Weiss; Roland Hart; Silas Mann; Kathleen Durkin; Steven H. Baete; Fernando E. Boada; Afia Genfi; Jillian Autea; Jennifer Newman; Desmond J. Oathes; Steven E. Lindley; Duna Abu-Amara; Bruce A. Arnow; Nicolas Crossley; Joachim Hallmayer; Silvia Fossati; Barbara O. Rothbaum; Charles R. Marmar; Edward T. Bullmore; Ruth O’Hara

doi:10.1126/scitranslmed.aal3236

Research ArticlePsychiatry

Using fMRI connectivity to define a treatment-resistant form of post-traumatic stress disorder

View ORCID ProfileAmit Etkin ¹,²,³,⁴,*,†,
View ORCID ProfileAdi Maron-Katz¹,²,³,⁴,*,
View ORCID ProfileWei Wu ¹,²,³,⁴,⁵,*,
Gregory A. Fonzo ¹,²,³,⁴,*,
View ORCID ProfileJulia Huemer¹,²,³,*,
View ORCID ProfilePetra E. Vértes ⁶,⁷,⁸,*,
Brian Patenaude¹,²,³,⁴,
View ORCID ProfileJonas Richiardi⁹,¹⁰,
Madeleine S. Goodkind¹¹,¹²,
View ORCID ProfileCorey J. Keller¹,²,³,⁴,
View ORCID ProfileJaime Ramos-Cejudo⁴,¹³,
View ORCID ProfileYevgeniya V. Zaiko¹,²,³,
Kathy K. Peng¹,³,
Emmanuel Shpigel¹,²,³,⁴,
View ORCID ProfileParker Longwell¹,²,³,⁴,
View ORCID ProfileRuss T. Toll ¹,²,³,⁴,
View ORCID ProfileAllison Thompson¹,
Sanno Zack¹,
Bryan Gonzalez⁴,¹³,
View ORCID ProfileRaleigh Edelstein¹,²,³,⁴,
Jingyun Chen⁴,¹³,
View ORCID ProfileIrene Akingbade¹,³,⁴,
Elizabeth Weiss¹,³,
Roland Hart⁴,¹³,
View ORCID ProfileSilas Mann⁴,¹³,
Kathleen Durkin⁴,¹³,
View ORCID ProfileSteven H. Baete⁴,¹¹,¹²,
View ORCID ProfileFernando E. Boada⁴,¹⁴,¹⁵,
Afia Genfi⁴,¹³,
Jillian Autea¹,²,³,⁴,
View ORCID ProfileJennifer Newman⁴,¹³,
View ORCID ProfileDesmond J. Oathes¹⁶,
View ORCID ProfileSteven E. Lindley¹,³,
View ORCID ProfileDuna Abu-Amara⁴,¹³,
View ORCID ProfileBruce A. Arnow¹,
View ORCID ProfileNicolas Crossley¹⁷,¹⁸,
View ORCID ProfileJoachim Hallmayer¹,²,³,
View ORCID ProfileSilvia Fossati⁴,¹³,
Barbara O. Rothbaum¹⁹,
Charles R. Marmar ⁴,¹³,
View ORCID ProfileEdward T. Bullmore⁶,²⁰,²¹ and
View ORCID ProfileRuth O’Hara ¹,³

¹Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.
²Wu Tsai Neurosciences Institute at Stanford, Stanford University, Stanford, CA 94304, USA.
³Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.
⁴Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.
⁵School of Automation Science and Engineering, South China University of Technology, Guangzhou, Guangdong 510640, China.
⁶Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 0SZ, UK.
⁷School of Mathematical Sciences, Queen Mary University of London, London E1 4NS, UK.
⁸The Alan Turing Institute, London NW1 2DB, UK.
⁹Department of Medical Radiology, Lausanne University Hospital, Lausanne, Switzerland.
¹⁰Advanced Clinical Imaging Technology, Siemens Healthcare AG, Lausanne, Switzerland.
¹¹New Mexico Veterans Affairs Healthcare System, Albuquerque, NM 87108, USA.
¹²Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, NM 87131, USA.
¹³Department of Psychiatry, New York University Langone School of Medicine, New York, NY 10016, USA.
¹⁴Center for Advanced Imaging Innovation and Research (CAI2R), NYU School of Medicine, New York, NY 10016, USA.
¹⁵Center for Biomedical Imaging, Department of Radiology, NYU School of Medicine, New York, NY 10016, USA.
¹⁶Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
¹⁷Department of Psychiatry, School of Medicine, Pontificia Universidad Católica de Chile, 6513677 Santiago, Chile.
¹⁸Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
¹⁹Trauma and Anxiety Recovery Program, Department of Psychiatry, Emory University School of Medicine, Atlanta, GA 30322, USA.
²⁰Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge CB21 5EF, UK.
²¹ImmunoPsychiatry, Alternative Discovery and Development, GlaxoSmithKline, Stevenage SG1 2NY, UK.

↵†Corresponding author. Email: amitetkin{at}stanford.edu

↵* These authors contributed equally to this work.

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Science Translational Medicine 03 Apr 2019:
Vol. 11, Issue 486, eaal3236
DOI: 10.1126/scitranslmed.aal3236

Amit Etkin

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

2Wu Tsai Neurosciences Institute at Stanford, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

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For correspondence: amitetkin@stanford.edu

Adi Maron-Katz

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

2Wu Tsai Neurosciences Institute at Stanford, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

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Wei Wu

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

2Wu Tsai Neurosciences Institute at Stanford, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

5School of Automation Science and Engineering, South China University of Technology, Guangzhou, Guangdong 510640, China.

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Gregory A. Fonzo

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

2Wu Tsai Neurosciences Institute at Stanford, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

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Julia Huemer

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

2Wu Tsai Neurosciences Institute at Stanford, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

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Petra E. Vértes

6Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 0SZ, UK.

7School of Mathematical Sciences, Queen Mary University of London, London E1 4NS, UK.

8The Alan Turing Institute, London NW1 2DB, UK.

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Brian Patenaude

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

2Wu Tsai Neurosciences Institute at Stanford, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

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Jonas Richiardi

9Department of Medical Radiology, Lausanne University Hospital, Lausanne, Switzerland.

10Advanced Clinical Imaging Technology, Siemens Healthcare AG, Lausanne, Switzerland.

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Madeleine S. Goodkind

11New Mexico Veterans Affairs Healthcare System, Albuquerque, NM 87108, USA.

12Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, NM 87131, USA.

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Corey J. Keller

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

2Wu Tsai Neurosciences Institute at Stanford, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

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Jaime Ramos-Cejudo

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

13Department of Psychiatry, New York University Langone School of Medicine, New York, NY 10016, USA.

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Yevgeniya V. Zaiko

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

2Wu Tsai Neurosciences Institute at Stanford, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

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Kathy K. Peng

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

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Emmanuel Shpigel

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

2Wu Tsai Neurosciences Institute at Stanford, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

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Parker Longwell

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

2Wu Tsai Neurosciences Institute at Stanford, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

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Russ T. Toll

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

2Wu Tsai Neurosciences Institute at Stanford, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

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Allison Thompson

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

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Sanno Zack

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

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Bryan Gonzalez

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

13Department of Psychiatry, New York University Langone School of Medicine, New York, NY 10016, USA.

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Raleigh Edelstein

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

2Wu Tsai Neurosciences Institute at Stanford, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

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Jingyun Chen

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

13Department of Psychiatry, New York University Langone School of Medicine, New York, NY 10016, USA.

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Irene Akingbade

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

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Elizabeth Weiss

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

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Roland Hart

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

13Department of Psychiatry, New York University Langone School of Medicine, New York, NY 10016, USA.

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Silas Mann

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

13Department of Psychiatry, New York University Langone School of Medicine, New York, NY 10016, USA.

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Kathleen Durkin

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

13Department of Psychiatry, New York University Langone School of Medicine, New York, NY 10016, USA.

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Steven H. Baete

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

11New Mexico Veterans Affairs Healthcare System, Albuquerque, NM 87108, USA.

12Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, NM 87131, USA.

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Fernando E. Boada

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

14Center for Advanced Imaging Innovation and Research (CAI2R), NYU School of Medicine, New York, NY 10016, USA.

15Center for Biomedical Imaging, Department of Radiology, NYU School of Medicine, New York, NY 10016, USA.

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Afia Genfi

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

13Department of Psychiatry, New York University Langone School of Medicine, New York, NY 10016, USA.

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Jillian Autea

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

2Wu Tsai Neurosciences Institute at Stanford, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

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Jennifer Newman

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

13Department of Psychiatry, New York University Langone School of Medicine, New York, NY 10016, USA.

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Desmond J. Oathes

16Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.

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Steven E. Lindley

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

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Duna Abu-Amara

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

13Department of Psychiatry, New York University Langone School of Medicine, New York, NY 10016, USA.

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Bruce A. Arnow

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

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Nicolas Crossley

17Department of Psychiatry, School of Medicine, Pontificia Universidad Católica de Chile, 6513677 Santiago, Chile.

18Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.

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Joachim Hallmayer

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

2Wu Tsai Neurosciences Institute at Stanford, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

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Silvia Fossati

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

13Department of Psychiatry, New York University Langone School of Medicine, New York, NY 10016, USA.

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Barbara O. Rothbaum

19Trauma and Anxiety Recovery Program, Department of Psychiatry, Emory University School of Medicine, Atlanta, GA 30322, USA.

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Charles R. Marmar

4Steven and Alexandra Cohen Veterans Center for Post-traumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York, NY 10016, USA.

13Department of Psychiatry, New York University Langone School of Medicine, New York, NY 10016, USA.

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Edward T. Bullmore

6Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 0SZ, UK.

20Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge CB21 5EF, UK.

21ImmunoPsychiatry, Alternative Discovery and Development, GlaxoSmithKline, Stevenage SG1 2NY, UK.

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Ruth O’Hara

1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.

3Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94394, USA.

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A subgroup of patients with post-traumatic stress disorder, characterized by a particular brain and behavioral signature, showed a poor treatment outcome.

Using fMRI connectivity to define a treatment-resistant form of post-traumatic stress disorder

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