Intrusive Traumatic Re-Experiencing Domain: Functional Connectivity Feature Classification by the ENIGMA PTSD Consortium

Benjamin Suarez-Jimenez; Amit Lazarov; Xi Zhu; Sigal Zilcha-Mano; Yoojean Kim; Claire E Marino; Pavel Rjabtsenkov; Shreya Y Bavdekar; Daniel S Pine; Yair Bar-Haim; Christine L Larson; Ashley A Huggins; Terri deRoon-Cassini; Carissa Tomas; Jacklynn Fitzgerald; Mitzy Kennis; Tim Varkevisser; Elbert Geuze; Yann Quidé; Wissam El Hage; Xin Wang; Erin N O'Leary; Andrew S Cotton; Hong Xie; Chiahao Shih; Seth G Disner; Nicholas D Davenport; Scott R Sponheim; Saskia B J Koch; Jessie L Frijling; Laura Nawijn; Mirjam van Zuiden; Miranda Olff; Dick J Veltman; Evan M Gordon; Geoffery May; Steven M Nelson; Meilin Jia-Richards; Yuval Neria; Rajendra A Morey

doi:10.1016/j.bpsgos.2023.05.006

Intrusive Traumatic Re-Experiencing Domain: Functional Connectivity Feature Classification by the ENIGMA PTSD Consortium

Biol Psychiatry Glob Open Sci. 2023 Jun 8;4(1):299-307. doi: 10.1016/j.bpsgos.2023.05.006. eCollection 2024 Jan.

Authors

Benjamin Suarez-Jimenez¹, Amit Lazarov^{2

3}, Xi Zhu³, Sigal Zilcha-Mano⁴, Yoojean Kim⁵, Claire E Marino¹, Pavel Rjabtsenkov¹, Shreya Y Bavdekar¹, Daniel S Pine⁶, Yair Bar-Haim^{2

7}, Christine L Larson⁸, Ashley A Huggins⁹, Terri deRoon-Cassini¹⁰, Carissa Tomas¹⁰, Jacklynn Fitzgerald¹¹, Mitzy Kennis^{12

13}, Tim Varkevisser^{12

13}, Elbert Geuze^{12

13}, Yann Quidé^{14

15}, Wissam El Hage^{16

17}, Xin Wang¹⁸, Erin N O'Leary¹⁸, Andrew S Cotton¹⁸, Hong Xie¹⁸, Chiahao Shih¹⁸, Seth G Disner¹⁹, Nicholas D Davenport¹⁹, Scott R Sponheim¹⁹, Saskia B J Koch²⁰, Jessie L Frijling²¹, Laura Nawijn^{21

22}, Mirjam van Zuiden²¹, Miranda Olff^{21

23}, Dick J Veltman²², Evan M Gordon²⁴, Geoffery May²⁵, Steven M Nelson²⁶, Meilin Jia-Richards²⁷, Yuval Neria³, Rajendra A Morey⁹

Affiliations

¹ Del Monte Institute for Neuroscience, Department of Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, New York.
² Department of Clinical Psychology, School of Psychological Sciences, Tel-Aviv University, Tel-Aviv, Israel.
³ Department of Psychiatry, Columbia University Irving Medical Center and New York State Psychiatric Institute, New York, New York.
⁴ Department of Psychology, University of Haifa, Mount Carmel, Haifa, Israel.
⁵ Department of Psychiatry, New York State Psychiatric Institute, New York, New York.
⁶ Section on Developmental Affective Neuroscience, National Institute of Mental Health, Bethesda, Maryland.
⁷ Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
⁸ University of Wisconsin-Milwaukee, Milwaukee, Wisconsin.
⁹ Duke University, Durham, North Carolina.
¹⁰ Medical College of Wisconsin, Milwaukee, Wisconsin.
¹¹ Marquette University, Milwaukee, Wisconsin.
¹² Brain Research and Innovation Centre, Ministry of Defence, Utrecht, the Netherlands.
¹³ Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands.
¹⁴ School of Psychology, University of New South Wales Sydney, Sydney, New South Wales, Australia.
¹⁵ Neuroscience Research Australia, Randwick, New South Wales, Australia.
¹⁶ Unité Mixte de Recherche 1253, Institut National de la Santé et de la Recherche Médicale, Université de Tours, Tours, France.
¹⁷ Centre d'investigation Clinique 1415, Institut National de la Santé et de la Recherche Médicale, Centre Hospitalier Régional Universitaire de Tours, Tours, France.
¹⁸ University of Toledo, Toledo, Ohio.
¹⁹ Minneapolis VA Health Care System, Minneapolis, Minnesota.
²⁰ Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, the Netherlands.
²¹ Department of Psychiatry, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands.
²² Department of Psychiatry, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
²³ ARQ National Psychotrauma Centre, Diemen, the Netherlands.
²⁴ Department of Radiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
²⁵ VISN 17 Center of Excellence for Research on Returning War Veterans, U.S. Department of Veterans Affairs, Waco, Texas.
²⁶ Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
²⁷ Department of Psychology and Neuroscience, Baylor University, Waco, Texas.

Abstract

Background: Intrusive traumatic re-experiencing domain (ITRED) was recently introduced as a novel perspective on posttraumatic psychopathology, proposing to focus research of posttraumatic stress disorder (PTSD) on the unique symptoms of intrusive and involuntary re-experiencing of the trauma, namely, intrusive memories, nightmares, and flashbacks. The aim of the present study was to explore ITRED from a neural network connectivity perspective.

Methods: Data were collected from 9 sites taking part in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) PTSD Consortium (n= 584) and included itemized PTSD symptom scores and resting-state functional connectivity (rsFC) data. We assessed the utility of rsFC in classifying PTSD, ITRED-only (no PTSD diagnosis), and trauma-exposed (TE)-only (no PTSD or ITRED) groups using a machine learning approach, examining well-known networks implicated in PTSD. A random forest classification model was built on a training set using cross-validation, and the averaged cross-validation model performance for classification was evaluated using the area under the curve. The model was tested using a fully independent portion of the data (test dataset), and the test area under the curve was evaluated.

Results: rsFC signatures differentiated TE-only participants from PTSD and ITRED-only participants at about 60% accuracy. Conversely, rsFC signatures did not differentiate PTSD from ITRED-only individuals (45% accuracy). Common features differentiating TE-only participants from PTSD and ITRED-only participants mainly involved default mode network-related pathways. Some unique features, such as connectivity within the frontoparietal network, differentiated TE-only participants from one group (PTSD or ITRED-only) but to a lesser extent from the other group.

Conclusions: Neural network connectivity supports ITRED as a novel neurobiologically based approach to classifying posttrauma psychopathology.

Keywords: ITRED; Machine learning; PTSD; Re-experiencing; Resting-state functional connectivity; Trauma exposure.

Abstract

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