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

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