Abstract
Although resilience is a dynamic process of recovery after trauma, in most studies it is conceptualized as the absence of specific psychopathology following trauma. Here, using the emergency department AURORA study (n = 1,835 with 63% women), we took a longitudinal, dynamic and transdiagnostic approach to define a static resilience (r) factor, which could explain greater than 50% of variance in mental well-being 6 months following trauma and a dynamic resilience factor, which represented recovery from initial symptoms. We then assessed its neurobiological profile across threat, inhibition and reward processes using functional magnetic resonance imaging collected 2 weeks post-trauma (n = 260). Our whole-brain and study-wide Bonferroni-corrected results suggest that resilience is promoted by activation of regions involved in higher-level cognitive functioning, reward valuation and salience detection in response to reward, whereas resilience is hampered by posterior default mode network activation to threat and reward. These findings serve to generate new hypotheses for brain mechanisms that could promote dynamic and multifaceted components of resilience following trauma.
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Data availability
We agree to make materials, data and associated protocols promptly available without undue qualifications. The data and/or research tools used in the preparation of this manuscript were obtained from the NDA. The NDA is a collaborative informatics system created by the NIH to provide a national resource to support and accelerate research in mental health. The dataset identifier(s) include the NIMH Data Archive digital object identifier 10.15154/zwyn-rb26. The masks used for the ROI analyses are freely available. The Hammers atlas is available via https://brain-development.org/brain-atlases/ (ref. 72), the CITI168 subcortical atlas via https://osf.io/r2hvk/wiki/home/ (ref. 73), the WFUPickAtlas via https://www.nitrc.org/projects/wfu_pickatlas (ref. 74) and the Harvard/Oxford atlas via https://neurovault.org/collections/262/ (ref. 75). REX software is available via https://www.nitrc.org/projects/rex/ (ref. 19).
Code availability
We agree to make code promptly available without undue qualifications. More information is available at https://github.com/sjhvanrooij/rfactor (ref. 76).
Change history
26 April 2024
A Correction to this paper has been published: https://doi.org/10.1038/s44220-024-00258-6
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Acknowledgements
The investigators thank the trauma survivors participating in the AURORA study. Their time and effort during a challenging period of their lives make our efforts to improve recovery for future trauma survivors possible. The AURORA project was supported by the National Institute of Mental Health (NIMH) under U01MH110925, the US Army MRMC, One Mind, and the Mayday Fund. The authors that were supported financially by funding for the AURORA project are as follows: R.C.K., K.J.R., K.C.K., S.A.M., S.L.H., F.L.B., X.A., J.S.S., T.C.N., G.D.C., T.J., S.D.L., L.T.G., K.A.B., S.L.R., J.P.H., A.B.S., C.L., P.I.M., P.L.H., S.S., C.W.J., B.E.P., R.A.S., V.P.M., J.L.P., M.J.S., E.H., C.P., D.A.P., R.C.M., R.M.D., N.K.R., B.J.O., L.D.S., S.E.B., J.J., D.A.P., J.F.S. and S.E.H. This paper was also supported by the NIMH under K01MH121653 (S.J.H.R.). The content is solely responsibility of the authors and does not necessarily represent the official views of any of the funders. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Verily Life Sciences and Mindstrong Health provided some of the hardware and software used to perform study assessments. The Many Brains Project provided software for neurocognitive assessments. This paper reflects the views of the authors and may not reflect the opinions or views of the NIH or of the submitters submitting original data to the NIMH Data Archive (NDA).
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S.A.M., R.C.K., K.J.R., K.C.K., S.J.H.v.R., J.S.S., J.L.S., C.A.H., T.D.E., N.H., V.M., L.L., T.J., S.L.H. and S.B. contributed to the conceptualization, including formulation or evolution of overarching research goals and aims, of the study. F.L.B., X.A., T.C.N., G.D.C., S.D.L., L.T.G., K.A.B., S.L.R., J.J., D.A.P., J.F.S., S.E.H., S.A.M., R.C.K., K.J.R., K.C.K., S.J.H.v.R., J.S.S, J.L.S., C.A.H., T.D.E., N.H., V.M., L.L., T.J., S.L.H. and S.B. contributed to the methodology of the study, including development or design of methodology and creation of models. S.J.H.v.R., J.S.S, J.L.S., C.A.H., T.D.E., N.H., V.M., L.L., T.J., S.L.H., S.B. and K.J.R. contributed to the neuroimagingdata collection, formal analyses and validation of the study. S.L.H., F.L.B., X.A., J.S.S., T.C.N., G.D.C., T.J., S.D.L., L.T.G., K.A.B., S.L.R., J.P.H., A.B.S., C.L., P.I.M.Jr, P.L.H., S.S., C.W.J., B.E.P., R.A.S., J.L.P., M.J.S., E.H., C.P., D.A.P., R.C.M., R.M.D., N.K.R., B.J.O., L.D.S., S.A.M., R.C.K., K.J.R. and K.C.K. conducted the research and investigation process, specifically, performing the experiments or data and evidence collection. S.L.H., F.L.B., X.A., J.S.S., T.C.N., G.D.C., T.J., S.D.L., L.T.G., K.A.B., S.L.R., J.P.H., A.B.S., C.L., P.I.M.Jr, P.L.H., S.S., C.W.J., B.E.P., R.A.S., J.L.P., M.J.S., E.H., C.P., D.A.P., R.C.M., R.M.D., N.K.R., B.J.O., L.D.S., S.A.M., R.C.K., K.J.R. and K.C.K. provided the resources for the study, including provision of study materials, patients, laboratory samples, instrumentation, computing resources or other analysis tools. S.L.H., F.L.B., X.A., J.S.S., T.C.N., G.D.C., T.J., S.D.L., L.T.G., K.A.B., S.L.R., S.A.M., R.C.K., K.J.R. and K.C.K. were responsible for data curation, including management activities to annotate, scrub data and maintain research data for initial use and later reuse. S.J.H.v.R., J.S.S., J.L.S., C.A.H., N.H., T.J. and K.J.R. were responsible for writing the original draft, including prepration, creation and presentation of the published work, and writing initial draft. All authors contributed to the paper by reviewing and editing the original draft. S.J.H.v.R., J.S.S., J.L.S. and C.A.H. were responsible for data visualization, including preparing, creating and presenting the published work, specifically, visualization and data presentation. S.A.M., R.C.K., K.J.R., K.C.K., S.J.H.v.R. and J.S.S. were responsible for supervision, including oversight and leadership for the research activity planning and execution, including mentorship external to the core team. S.L.H., F.L.B., J.S.S., T.J., J.P.H., A.B.S., C.L. P.I.M.Jr, P.L.H., S.S., C.W.J., B.E.P., R.A.S., J.L.P., M.J.S., E.H., C.P., D.A.P., R.C.M., R.M.D., N.K.R., N.J.O., L.D.S. and S.B. were responsible for project administration, including management and coordination, responsibility for the research activity planning and execution. S.A.M., R.C.K., K.J.R. and K.C.K. were responsible for acquisition of the financial support for the project leading to this publication. S.J.H.v.R. was responsible for funding supporting her effort on this publication.
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T.C.N. has received research support from NIH, VA and Rainwater Charitable Foundation and consulting income from Jazz Pharmaceuticals. In the past 3 years, G.D.C. has received research funding from the NSF, NIH and LifeBell AI and unrestricted donations from AliveCor Inc., Amazon Research, the Center for Discovery, the Gates Foundation, Google, the Gordon and Betty Moore Foundation, MathWorks, Microsoft Research, Nextsense Inc, One Mind Foundation, the Rett Research Foundation and Samsun Research. G.D.C. has financial interest in AliveCor Inc. and Nextsense Inc. He is also the CTO of MindChild Medical and CSO of LifeBell AI and has ownership in both companies. These relationships are unconnected to the current work. L.T.G. receives funding from the National Institute of Mental Health (R01 MH121617) and am on the board of the Many Brains Project. Her family also has equity in Intelerad Medical Systems, Inc. S.L.R. reports grants from NIH during the conduct of the study; personal fees from the Society of Biological Psychiatry paid roles as secretary, other from Oxford University Press royalties, other from American Psychiatric Publishing Inc. royalties, other from the Veterans Administration per diem for oversight committee and other from Community Psychiatry/Mindpath Health paid board service, including equity outside the submitted work; other from National Association of Behavioral Healthcare for paid Board service; other from Springer Publishing royalties; and Leadership roles on Board or Council for SOBP, the Anxiety and Depression Association of America and the National Network of Depression Centers. S.S. has received funding from the Florida Medical Malpractice Joint Underwriter’s Association Dr. Alvin E. Smith Safety of Healthcare Services Grant, Allergan Foundation, the NIH/NIA-funded Jacksonville Aging Studies Center (JAX-ASCENT; R33AG05654), the Substance Abuse and Mental health Services Administration (1H79TI083101-01) and the Florida Blue Foundation. C.W.J. has no competing interest related to this work, though he has been an investigator on studies funded by AstraZeneca, Vapotherm, Abbott and Ophirex. J.J. receives consulting payments from Janssen Pharmaceuticals. Over the past 3 years, D.A.P. has received consulting fees from Albright Stonebridge Group, Boehringer Ingelheim, Compass Pathways, Concert Pharmaceuticals, Engrail Therapeutics, Neumora Therapeutics (former BlackThorn Therapeutics), Neurocrine Biosciences, Neuroscience Software, Otsuka Pharmaceuticals and Takeda Pharmaceuticals; honoraria from the Psychonomic Society (for editorial work) and Alkermes, and research funding from NIMH, Dana Foundation, Brain and Behavior Research Foundation and Millennium Pharmaceuticals. In addition, he has received stock option from Neumora Therapeutics (former BlackThorn Therapeutics), Compass Pathways, Engrail Therapeutics, and Neuroscience Software. S.E.H. has no competing interest related to this work, though in the past 3 years he has received research funding from Aptinyx and Arbor Medical Innovations and consulting payments from Aptinyx, heron Therapeutics and Eli Lilly. In the past 3 years, R.C.K. was a consultant for Cambridge Health Alliance, Canandaigua VA Medical Center, Holmusk, Partners Healthcare, Inc., RallyPoint Networks, Inc. and Sage Therapeutics. He has stock options in Cerebral Inc., Mirah, PYM and Roga Sciences. K.C.K’s research has been supported by the Robert Wood Johnson Foundation, the Kaiser Family Foundation, the Harvard Center on the Developing Child, Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, the NIH, One Mind, The Anonymous Foundation and Cohen Veterans Bioscience. She has been a paid consultant for Baker Hostetler, Discovery Vitality and the Department of Justice. She has been a paid external reviewer for the Chan Zuckerberg Foundation, the University of Cape Town and Capita Ireland. She has had paid speaking engagements in the past 3 years with the American Psychological Association, European Central Bank. Sigmund Freud University—Milan, Cambridge Health Alliance and Coverys. She receives royalties from Guilford Press and Oxford University Press. S.A.M. served as a consultant for Walter Reed Army Institute for Research and for Arbor Medical Innovations. K.J.R. has performed scientific consultation for Bioxcel, Bionomics, Acer and Jazz Pharm; serves on Scientific Advisory Boards for Sage, Boehringer Ingelheim, Senseye and the Brain Research Foundation; and has received sponsored research support from Alto Neuroscience. The other authors declare no competing interests.
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van Rooij, S.J.H., Santos, J.L., Hinojosa, C.A. et al. Defining the r factor for post-trauma resilience and its neural predictors. Nat. Mental Health (2024). https://doi.org/10.1038/s44220-024-00242-0
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DOI: https://doi.org/10.1038/s44220-024-00242-0
