title: Development and application of a diagnostic algorithm for posttraumatic stress disorder.
abstract: Intact cognitive functions rely on synchronous neural activity; conversely, alterations in synchrony are thought to underlie psychopathology. We recently demonstrated that anomalies in synchronous neural interactions (SNI) determined by magnetoencephalography represent a putative PTSD biomarker. Here we develop and apply a regression-based diagnostic algorithm to further validate SNI as a PTSD biomarker in 432 veterans (235 controls; 138 pure PTSD; 59 PTSD plus comorbid disorders). Correlation coefficients served as proximities in multidimensional scaling (MDS) to obtain a two-dimensional representation of the data. In addition, least absolute shrinkage and selection operator (LASSO) regression was used to derive a diagnostic algorithm for PTSD. Performance of this algorithm was assessed by the area under the receiver operating characteristic (ROC) curves, sensitivity, and specificity in 1000 randomly divided testing and validation datasets and in independent samples. MDS revealed that individuals with PTSD, regardless of comorbid psychiatric conditions, are highly distinct from controls. Similarly, application of the LASSO regression-derived prediction model demonstrated remarkable classification accuracy (AUCs≥0.93 for men, AUC=0.82 for women). Neural functioning in individuals with PTSD, regardless of comorbid psychiatric diagnoses, can be used as a diagnostic test to determine patient disease status, further validating SNI as a PTSD biomarker.
authors.affiliation: Brain Sciences Center, Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA; Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA; Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, USA. Electronic address: lisa.james2@va.gov.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: James
authors.affiliation: VA Cooperative Studies Program Palo Alto Coordinating Center, Mountain View, CA, USA; Department of Population Health, New York University School of Medicine, New York, NY, USA; Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: Ilana
authors.initials: I
authors.lastname: Belitskaya-Lévy
authors.affiliation: VA Cooperative Studies Program Palo Alto Coordinating Center, Mountain View, CA, USA; Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: VA Cooperative Studies Program Palo Alto Coordinating Center, Mountain View, CA, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Brain Sciences Center, Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA; Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, USA; Department of Psychology, University of Minnesota, Minneapolis, MN, USA; Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Engdahl
authors.affiliation: Brain Sciences Center, Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA; Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Arthur C
authors.initials: AC
authors.lastname: Leuthold
authors.affiliation: Brain Sciences Center, Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA; Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA; Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, USA; Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA; Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Apostolos P
authors.initials: AP
authors.lastname: Georgopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D015897:Comorbidity; D005260:Female; D006801:Humans; D015225:Magnetoencephalography / Q000379:methods*; D008297:Male; D001523:Mental Disorders / Q000453:epidemiology; D008875:Middle Aged; D015999:Multivariate Analysis; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013313:Stress Disorders, Post-Traumatic / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology; D014728:Veterans / Q000523:psychology; D055815:Young Adult
keywords: Biomarker; Magnetoencephalography; Posttraumatic stress disorder; ROC curve; Regression analysis; Veterans