Abstract
The objective of this research project is the identification of a physiological prodrome of post-traumatic stress disorder (PTSD) that has a reliability that could justify preemptive treatment in the sub-syndromal state. Because abnormalities in event-related potentials (ERPs) have been observed in fully expressed PTSD, the possible utility of abnormal ERPs in predicting delayed-onset PTSD was investigated. ERPs were recorded from military service members recently returned from Iraq or Afghanistan who did not meet PTSD diagnostic criteria at the time of ERP acquisition. Participants (n = 65) were followed for up to 1 year, and 7.7% of the cohorts (n = 5) were PTSD-positive at follow-up. The initial analysis of the receiver operating characteristic (ROC) curve constructed using ERP metrics was encouraging. The average amplitude to target stimuli gave an area under the ROC curve of greater than 0.8. Classification based on the Youden index, which is determined from the ROC, gave positive results. Using average target amplitude at electrode Cz yielded Sensitivity = 0.80 and Specificity = 0.87. A more systematic statistical analysis of the ERP data indicated that the ROC results may simply represent a fortuitous consequence of small sample size. Predicted error rates based on the distribution of target ERP amplitudes approached those of random classification. A leave-one-out cross validation using a Gaussian likelihood classifier with Bayesian priors gave lower values of sensitivity and specificity. In contrast with the ROC results, the leave-one-out classification at Cz gave Sensitivity = 0.65 and Specificity = 0.60. A bootstrap calculation, again using the Gaussian likelihood classifier at Cz, gave Sensitivity = 0.59 and Specificity = 0.68. Two provisional conclusions can be offered. First, the results can only be considered preliminary due to the small sample size, and a much larger study will be required to assess definitively the utility of ERP prodromes of PTSD. Second, it may be necessary to combine ERPs with other biomarkers in a multivariate metric to produce a prodrome that can justify preemptive treatment.
Highlights
Psychiatric practice has been reactive rather than preemptive
We address a specific question: can event-related potentials identify individuals at risk of delayed-onset post-traumatic stress disorder (PTSD)? As preceding questions we must ask whether an at-risk population can be identified and if there is evidence indicating that PTSD can, in some instances, present with delayed onset? It is the period between trauma exposure and the presentation of a fully expressed PTSD that provides the window of opportunity for preemptive treatment
Exclusion criteria included a history of head injury resulting in loss of consciousness for 60 min or more; a current Glasgow Coma Scale less than 13; visual acuity lower than 20/100 after correction; psychosis; active suicidal, or homicidal ideation; pregnancy; a diagnosis of postconcussional syndrome (PCS) according ICD-10, Patient Health Questionnaire-9 (PHQ-9) score greater than or equal to 10; and a PTSD Checklist-Military Version (PCL-M) score greater than or equal to 50, or a diagnosis of PTSD made by an experienced psychologist using the Clinician-Administered PTSD Scale (CAPS) based on the DSM-IV criteria
Summary
It has been recognized that a transition to preemptive psychiatry requires the identification of prodromes of psychiatric disorders that have a predictive reliability that justifies intervention in the absence of a fully expressed disorder. A prodrome is a premonitory manifestation of the disease. A prodromal symptom may or may not continue to be manifest once the full disease appears. The same disease may or may not manifest prodromal symptoms in different episodes.”. Prior research has investigated prodromes of several psychiatric disorders including psychosis [4,5,6,7], depression [8], autism [9, 10], dementia [11], alcoholism and substance abuse [1, 12], and post-traumatic stress disorder [PTSD [13,14,15]]
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