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.
Harnett NG, van Rooij SJH, Ely TD, Lebois LAM, Murty VP, Jovanovic T, Hill SB, Dumornay NM, Merker JB, Bruce SE, House SL, Beaudoin FL, An X, Zeng D, Neylan TC, Clifford GD, Linnstaedt SD, Germine LT, Bollen KA, Rauch SL, Lewandowski C, Hendry PL, Sheikh S, Storrow AB, Musey PI Jr, Haran JP, Jones CW, Punches BE, Swor RA, McGrath ME, Pascual JL, Seamon MJ, Mohiuddin K, Chang AM, Pearson C, Peak DA, Domeier RM, Rathlev NK, Sanchez LD, Pietrzak RH, Joormann J, Barch DM, Pizzagalli DA, Sheridan JF, Harte SE, Elliott JM, Kessler RC, Koenen KC, Mclean S, Ressler KJ, Stevens JS. Prognostic neuroimaging biomarkers of trauma-related psychopathology: resting-state fMRI shortly after trauma predicts future PTSD and depression symptoms in the AURORA study. Neuropsychopharmacology. 2021 Jan 21. doi: 10.1038/s41386-020-00946-8. Epub ahead of print.