Abstract

Importance Uncovering objective correlates of PTSD severity may improve early case detection and treatment decisions. Objective To test the ability of an innovative analytic approach to select a set of multimodal biomarkers that efficiently differentiates PTSD subtypes shortly after traumatic event. Design Observational cohort study of general hospital emergency department (ED) admissions for traumatic events seen between 2014 and 2018. A three-staged semi-unsupervised computational method (alias “3C”) was used to categorize trauma survivors based on current PTSD diagnostics, derive clusters of self-reported depression and anxiety symptoms related to these categories, and to predict and classify participants’ cluster membership using concurrently collected neurocognitive and neuroimaging data. 256 features were extracted from psychometrics, neurocognitive and neuroimaging (structural and functional) data obtained within a month of trauma exposure. Setting Information on consecutive ED trauma admission was used to initiate telephone screening interviews, followed, in eligible survivors, by clinical, neurocognitive and brain imaging assessments. Participants 101 adults survivors of traumatic events (78% motor-vehicle accidents, 51 females, average age = 34.80; age range = 18 – 65). Main Outcomes and Measures Objective features (alias “potential biomarkers”) that best differentiate clusters membership were derived from this set. Importance analysis, classification trees, and one-way ANOVA were used to test the potential biomarkers’ contributions. Results Entorhinal and rostral anterior cingulate cortical volumes; executive function, cognitive flexibility; and the amygdala’s functional connectivity with the insula and thalamus best differentiated between the two participants severity clusters. Cross-validation established the results’ robustness and consistency within this sample. Conclusions and Relevance This work demonstrates the ability of multi-domain analytic assessment using standardized and objectively measured neuro-behavioral features to differentiate PTSD subgroups at the early aftermath of traumatic events. Differentiating features revealed by this work are consistent with previously reported neurobehavioral PTSD attributes. Trial Registration Neurobehavioral Moderators of Post-traumatic Disease Trajectories. ClinicalTrials.gov registration number: NCT03756545. https://clinicaltrials.gov/ct2/show/NCT03756545 Key Points Question Can we computationally derive objective classifiers of post-traumatic stress disorder (PTSD) shortly after traumatic event? Findings 256 features were extracted from psychometrics, neurocognitive and neuroimaging data obtained from 101 recent trauma survivors. A semi-unsupervised computational method (3C) successfully categorized cases based on PTSD diagnostics, derived clusters of severe and mild PTSD, and revealed neurocognitive and neuroimaging features that efficiently classified patients’ status. Meaning Biomarkers revealed by the 3C offer objective classifiers of post-traumatic psychiatric morbidity shortly after traumatic event. They also map into previously documented neurobehavioral PTSD features, thus support the future use of objective measurements to more precisely identify post-traumatic psychopathology.