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Prognostic neuroimaging biomarkers of trauma-related psychopathology: resting-state fMRI shortly after trauma predicts future PTSD and depression symptoms in the AURORA study


Neurobiological markers of future susceptibility to posttraumatic stress disorder (PTSD) may facilitate identification of vulnerable individuals in the early aftermath of trauma. Variability in resting-state networks (RSNs), patterns of intrinsic functional connectivity across the brain, has previously been linked to PTSD, and may thus be informative of PTSD susceptibility. The present data are part of an initial analysis from the AURORA study, a longitudinal, multisite study of adverse neuropsychiatric sequalae. Magnetic resonance imaging (MRI) data from 109 recently (i.e., ~2 weeks) traumatized individuals were collected and PTSD and depression symptoms were assessed at 3 months post trauma. We assessed commonly reported RSNs including the default mode network (DMN), central executive network (CEN), and salience network (SN). We also identified a proposed arousal network (AN) composed of a priori brain regions important for PTSD: the amygdala, hippocampus, mamillary bodies, midbrain, and pons. Primary analyses assessed whether variability in functional connectivity at the 2-week imaging timepoint predicted 3-month PTSD symptom severity. Left dorsolateral prefrontal cortex (DLPFC) to AN connectivity at 2 weeks post trauma was negatively related to 3-month PTSD symptoms. Further, right inferior temporal gyrus (ITG) to DMN connectivity was positively related to 3-month PTSD symptoms. Both DLPFC-AN and ITG-DMN connectivity also predicted depression symptoms at 3 months. Our results suggest that, following trauma exposure, acutely assessed variability in RSN connectivity was associated with PTSD symptom severity approximately two and a half months later. However, these patterns may reflect general susceptibility to posttraumatic dysfunction as the imaging patterns were not linked to specific disorder symptoms, at least in the subacute/early chronic phase. The present data suggest that assessment of RSNs in the early aftermath of trauma may be informative of susceptibility to posttraumatic dysfunction, with future work needed to understand neural markers of long-term (e.g., 12 months post trauma) dysfunction. Furthermore, these findings are consistent with neural models suggesting that decreased top-down cortico-limbic regulation and increased network-mediated fear generalization may contribute to ongoing dysfunction in the aftermath of trauma.

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Fig. 1: Resting-state networks.
Fig. 2: Network-to-node connectivity of the default mode and arousal networks vary with 3-month posttraumatic stress severity.


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The authors would like to thank Rebecca Price, Adam Hively, Saswati Data, Suraj Oomman, and the other members of the UNC Institute for Trauma Recovery for their efforts and aide in this research. We would also like to thank research staff at McLean Hospital, Emory University, Temple University, and Wayne State University for their efforts and aide. We further express our gratitude to the participants and their families for their willingness to participate in this research.

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Design and conceptualization of study: RCK, KCK, SM, and KJR. Data acquisition, recruitment, and logistics: SBH, NMD, JBM, SEB, SLH, FLB, XA, DZ, TCN, GDC, SDL, KAB, SLR, CL, PLH, SS, ABS, PIM Jr., JPH, CWJ, BEP, RAS, MEM, JLP, MJS, KM, AMC, CP, DAP, RMD, NKR, and LDS. Data processing and statistical analyses: NGH, SVR, TDE, JSS. Data interpretation NGH, SVR, TDE, LAML, VPM, TJ, KJR, and JSS. Drafting of the paper: NGH, SVR, LAML, VPM, TJ, KJR, and JSS. All authors revised the paper critically for important intellectual context and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Nathaniel G. Harnett or Jennifer S. Stevens.

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Harnett, N.G., van Rooij, S.J.H., Ely, T.D. et al. Prognostic neuroimaging biomarkers of trauma-related psychopathology: resting-state fMRI shortly after trauma predicts future PTSD and depression symptoms in the AURORA study. Neuropsychopharmacol. 46, 1263–1271 (2021).

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