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      Identifying Electrophysiological Prodromes of Post-traumatic Stress Disorder: Results from a Pilot Study

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          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.

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          Most cited references 80

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          Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication.

          Little is known about lifetime prevalence or age of onset of DSM-IV disorders. To estimate lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the recently completed National Comorbidity Survey Replication. Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using the fully structured World Health Organization World Mental Health Survey version of the Composite International Diagnostic Interview. Nine thousand two hundred eighty-two English-speaking respondents aged 18 years and older. Lifetime DSM-IV anxiety, mood, impulse-control, and substance use disorders. Lifetime prevalence estimates are as follows: anxiety disorders, 28.8%; mood disorders, 20.8%; impulse-control disorders, 24.8%; substance use disorders, 14.6%; any disorder, 46.4%. Median age of onset is much earlier for anxiety (11 years) and impulse-control (11 years) disorders than for substance use (20 years) and mood (30 years) disorders. Half of all lifetime cases start by age 14 years and three fourths by age 24 years. Later onsets are mostly of comorbid conditions, with estimated lifetime risk of any disorder at age 75 years (50.8%) only slightly higher than observed lifetime prevalence (46.4%). Lifetime prevalence estimates are higher in recent cohorts than in earlier cohorts and have fairly stable intercohort differences across the life course that vary in substantively plausible ways among sociodemographic subgroups. About half of Americans will meet the criteria for a DSM-IV disorder sometime in their life, with first onset usually in childhood or adolescence. Interventions aimed at prevention or early treatment need to focus on youth.
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            Updating P300: an integrative theory of P3a and P3b.

             John Polich (2007)
            The empirical and theoretical development of the P300 event-related brain potential (ERP) is reviewed by considering factors that contribute to its amplitude, latency, and general characteristics. The neuropsychological origins of the P3a and P3b subcomponents are detailed, and how target/standard discrimination difficulty modulates scalp topography is discussed. The neural loci of P3a and P3b generation are outlined, and a cognitive model is proffered: P3a originates from stimulus-driven frontal attention mechanisms during task processing, whereas P3b originates from temporal-parietal activity associated with attention and appears related to subsequent memory processing. Neurotransmitter actions associating P3a to frontal/dopaminergic and P3b to parietal/norepinephrine pathways are highlighted. Neuroinhibition is suggested as an overarching theoretical mechanism for P300, which is elicited when stimulus detection engages memory operations.
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              Index for rating diagnostic tests.

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                Author and article information

                Affiliations
                1Traumatic Injury Research Program, Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences , Bethesda, MD, USA
                2The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. , Bethesda, MD, USA
                3Department of Medicine and Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences , Bethesda, MD, USA
                4Graduate School of Nursing, Uniformed Services University of the Health Sciences , Bethesda, MD, USA
                5Aquinas LLC , Berwyn, PA, USA
                Author notes

                Edited by: Kim T. Mueser, Boston University, USA

                Reviewed by: Jonathan K. Wynn, University of California Los Angeles, USA; Takako Mitsudo, Kyushu University, Japan

                *Correspondence: Paul Rapp, paul.rapp@ 123456usuhs.edu

                Specialty section: This article was submitted to Psychopathology, a section of the journal Frontiers in Psychiatry

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                15 May 2017
                2017
                : 8
                10.3389/fpsyt.2017.00071
                5430065
                Copyright © 2017 Wang, Costanzo, Rapp, Darmon, Bashirelahi, Nathan, Cellucci, Roy and Keyser.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Counts
                Figures: 2, Tables: 6, Equations: 21, References: 80, Pages: 14, Words: 11866
                Categories
                Psychiatry
                Original Research

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