title: Functional Neuroimaging Distinguishes Posttraumatic Stress Disorder from Traumatic Brain Injury in Focused and Large Community Datasets.
abstract: BACKGROUND
  Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are highly heterogeneous and often present with overlapping symptomology, providing challenges in reliable classification and treatment. Single photon emission computed tomography (SPECT) may be advantageous in the diagnostic separation of these disorders when comorbid or clinically indistinct.
  
  
  METHODS
  Subjects were selected from a multisite database, where rest and on-task SPECT scans were obtained on a large group of neuropsychiatric patients. Two groups were analyzed: Group 1 with TBI (n=104), PTSD (n=104) or both (n=73) closely matched for demographics and comorbidity, compared to each other and healthy controls (N=116); Group 2 with TBI (n=7,505), PTSD (n=1,077) or both (n=1,017) compared to n=11,147 without either. ROIs and visual readings (VRs) were analyzed using a binary logistic regression model with predicted probabilities inputted into a Receiver Operating Characteristic analysis to identify sensitivity, specificity, and accuracy. One-way ANOVA identified the most diagnostically significant regions of increased perfusion in PTSD compared to TBI. Analysis included a 10-fold cross validation of the protocol in the larger community sample (Group 2).
  
  
  RESULTS
  For Group 1, baseline and on-task ROIs and VRs showed a high level of accuracy in differentiating PTSD, TBI and PTSD+TBI conditions. This carefully matched group separated with 100% sensitivity, specificity and accuracy for the ROI analysis and at 89% or above for VRs. Group 2 had lower sensitivity, specificity and accuracy, but still in a clinically relevant range. Compared to subjects with TBI, PTSD showed increases in the limbic regions, cingulum, basal ganglia, insula, thalamus, prefrontal cortex and temporal lobes.
  
  
  CONCLUSIONS
  This study demonstrates the ability to separate PTSD and TBI from healthy controls, from each other, and detect their co-occurrence, even in highly comorbid samples, using SPECT. This modality may offer a clinical option for aiding diagnosis and treatment of these conditions.
authors.affiliation: Department of Research, Amen Clinics, Inc., Costa Mesa, California, United States of America.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Amen
authors.affiliation: Department of Radiology, University of California Los Angeles Medical Center, Los Angeles, California, United States of America.
authors.forename: Cyrus A
authors.initials: CA
authors.lastname: Raji
authors.affiliation: Department of Research, Amen Clinics, Inc., Costa Mesa, California, United States of America.
authors.forename: Kristen
authors.initials: K
authors.lastname: Willeumier
authors.affiliation: Department of Research, Amen Clinics, Inc., Costa Mesa, California, United States of America.
authors.forename: Derek
authors.initials: D
authors.lastname: Taylor
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of British Columbia, Lions Gate Hospital, North Vancouver, British Columbia, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Tarzwell
authors.affiliation: Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Newberg
authors.affiliation: The Synaptic Space, Denver, Colorado, United States of America; The International Society of Applied Neuroimaging, Denver, Colorado, United States of America.
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Henderson
mesh_terms: D000328:Adult; D015415:Biomarkers; D001930:Brain Injuries / Q000175:diagnosis*; D015897:Comorbidity; D016208:Databases, Factual; D003937:Diagnosis, Differential; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D008889:Military Personnel; D012372:ROC Curve; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013313:Stress Disorders, Post-Traumatic / Q000175:diagnosis*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D055815:Young Adult
chemical_list: D015415:Biomarkers