Using fMRI connectivity to define a treatment-resistant form of post-traumatic stress disorder
Open accessAbstract
A mechanistic understanding of the pathology of psychiatric disorders has been hampered by extensive heterogeneity in biology, symptoms, and behavior within diagnostic categories that are defined subjectively. We investigated whether leveraging individual differences in information-processing impairments in patients with post-traumatic stress disorder (PTSD) could reveal phenotypes within the disorder. We found that a subgroup of patients with PTSD from two independent cohorts displayed both aberrant functional connectivity within the ventral attention network (VAN) as revealed by functional magnetic resonance imaging (fMRI) neuroimaging and impaired verbal memory on a word list learning task. This combined phenotype was not associated with differences in symptoms or comorbidities, but nonetheless could be used to predict a poor response to psychotherapy, the best-validated treatment for PTSD. Using concurrent focal noninvasive transcranial magnetic stimulation and electroencephalography, we then identified alterations in neural signal flow in the VAN that were evoked by direct stimulation of that network. These alterations were associated with individual differences in functional fMRI connectivity within the VAN. Our findings define specific neurobiological mechanisms in a subgroup of patients with PTSD that could contribute to the poor response to psychotherapy.
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Combining psychotherapy with existing anxiety medication treatment does not seem to provide consistently superior benefits across anxiety disorders, but may be useful for those patient groups that do not adequately respond to CBT alone.
“This approach, however, does not seem to provide consistently superior benefits across anxiety disorders, but may be useful for those patient groups that do not adequately respond to CBT alone (Etkin et al., 2019;Tolin, 2017).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Etkin et al., 2019
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Research works printed but not linked: 3
- [1]APA, Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Press, ed. 4, 1994).
- [39]IOM, Treatment of Posttraumatic Stress Disorder: An Assessment of the Evidence (The National Academies Press, 2008).
- [80]Foa EB, Hembree EA, Rothbaum BO, Prolonged Exposure Therapy for PTSD (Oxford Univ. Press, ed. 1, 2007).
Cited by
Sorted by citations
Questions and controversies in the study of time-varying functional connectivity in resting fMRI
Lurie, D. J., Kessler, D., Bassett, D. S., Betzel, R. F., Breakspear, M., Kheilholz, S., Kucyi, A., Liégeois, R., Lindquist, M. A., McIntosh, A. R., et al. (2020) · Network Neuroscience · doi:10.1162/netn_a_00116 · Cited by 648 · see citing works
Zhang, Y., Wu, W., Toll, R. T., Naparstek, S., Maron-Katz, A., Watts, M., Gordon, J., Jeong, J., Astolfi, L., Shpigel, E., et al. (2020) · Nature Biomedical Engineering · doi:10.1038/s41551-020-00614-8 · Cited by 241 · see citing works
Self-citationSartori, S. B., & Singewald, N. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.107402 · Cited by 236 · see citing works
(2020) · Advances in Pharmacology · doi:10.1016/bs.apha.2020.04.003 · Cited by 18 · see citing works
- Authors
- Etkin, A., Maron-Katz, A., Wu, W., Fonzo, G. A., Huemer, J., Vértes, P. E., Patenaude, B., Richiardi, J., Goodkind, M. S., Keller, C. J., Ramos-Cejudo, J., Zaiko, Y. V., Peng, K. K., Shpigel, E., Longwell, P., Toll, R. T., Thompson, A., Zack, S., Gonzalez, B., Edelstein, R., Chen, J., Akingbade, I., Weiss, E., Hart, R., Mann, S., Durkin, K., Baete, S. H., Boada, F. E., Genfi, A., Autea, J., Newman, J., Oathes, D. J., Lindley, S. E., Abu-Amara, D., Arnow, B. A., Crossley, N., Hallmayer, J., Fossati, S., Rothbaum, B. O., Marmar, C. R., Bullmore, E. T., & O’Hara, R.
- Affiliations
- VA Palo Alto Health Care System (US)
- Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94304, USA.
- Queen Mary University of London (GB)
- Centre Hospitalier Universitaire Vaudois (CH)
- University of New Mexico (US)
- Steven 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.
- Stanford University (US)
- NYU Langone Health (US)
- University of Pennsylvania (US)
- Pontificia Universidad Católica de Chile (CL)
- Emory University (US)
- GlaxoSmithKline (United Kingdom) (GB)
- Corresponding author
- Etkin, Amit
- Wu, Wei
- Fonzo, Gregory A.
- Huemer, Julia
- Vértes, Petra E.
- ORCID
- Etkin, Amit
- Maron-Katz, Adi
- Wu, Wei
- Fonzo, Gregory A.
- Huemer, Julia
- Vértes, Petra E.
- Richiardi, Jonas
- Goodkind, Madeleine S.
- Keller, Corey J.
- Ramos-Cejudo, Jaime
- Zaiko, Yevgeniya V.
- Shpigel, Emmanuel
- Longwell, Parker
- Toll, Russ T.
- Thompson, Allison
- Edelstein, Raleigh
- Chen, Jingyun
- Akingbade, Irene
- Hart, Roland
- Mann, Silas
- Baete, Steven H.
- Boada, Fernando E.
- Newman, Jennifer
- Oathes, Desmond J.
- Lindley, Steven E.
- Abu-Amara, Duna
- Arnow, Bruce A.
- Crossley, Nicolas
- Hallmayer, Joachim
- Fossati, Silvia
- Rothbaum, Barbara O.
- Marmar, Charles R.
- Bullmore, Edward T.
- O’Hara, Ruth
- Venue
- Science Translational Medicine
- Published
- 2019-04-03
- Volume
- 11
- Issue
- 486
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC6980337
- OpenAlex
- W2928294493
- Cited by
- 103
- References
- 93
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 12 · 2023: 7 · 2022: 14 · 2021: 17 · 2020: 19 · 2019: 9
- FWCI
- 17.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- IRIS (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- National Institutes of Health (R01 MH091860, T32 MH019938)
- Medical Research Council (MR/K020706/1)
- National Science Foundation (DGE-1147470)
- National Key Research and Development Plan of China (2017YFB1002505)
- Steven A. and Alexandra M. Cohen Foundation
- funds from Ann and Peter Tarlton
- Sierra-Pacific Mental Illness Research, Education and Clinical Center (MIRECC) at the Palo Alto VA
- Cohen Veterans Bioscience
- Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- post-traumatic stress disorder, treatment-resistant PTSD, functional connectivity, ventral attention network, verbal memory impairment, word list learning, transcranial magnetic stimulation, EEG, individual differences, phenotypes
- MeSH terms
- Attention, Behavior, Brain Mapping, Electroencephalography, Humans, Magnetic Resonance Imaging, Nerve Net, Mental Recall, Rest, Stress Disorders, Post-Traumatic, Comorbidity, Treatment Outcome, Transcranial Magnetic Stimulation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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