Functional Neuroimaging Distinguishes Posttraumatic Stress Disorder from Traumatic Brain Injury in Focused and Large Community Datasets

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 sepa...

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Published inPloS one Vol. 10; no. 7; p. e0129659
Main Authors Amen, Daniel G., Raji, Cyrus A., Willeumier, Kristen, Taylor, Derek, Tarzwell, Robert, Newberg, Andrew, Henderson, Theodore A.
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 01.07.2015
Public Library of Science (PLoS)
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Online AccessGet full text
ISSN1932-6203
1932-6203
DOI10.1371/journal.pone.0129659

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Abstract 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. 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). 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. 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.
AbstractList 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.
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. 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). 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. 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.
BACKGROUNDTraumatic 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.METHODSSubjects 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).RESULTSFor 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.CONCLUSIONSThis 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.
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. 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). 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. 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.
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.
Audience Academic
Author Raji, Cyrus A.
Newberg, Andrew
Willeumier, Kristen
Tarzwell, Robert
Henderson, Theodore A.
Amen, Daniel G.
Taylor, Derek
AuthorAffiliation 2 Department of Radiology, University of California Los Angeles Medical Center, Los Angeles, California, United States of America
3 Department of Psychiatry, Faculty of Medicine, University of British Columbia, Lions Gate Hospital, North Vancouver, British Columbia, Canada
5 The Synaptic Space, Denver, Colorado, United States of America
6 The International Society of Applied Neuroimaging, Denver, Colorado, United States of America
Univ of Toledo, UNITED STATES
1 Department of Research, Amen Clinics, Inc., Costa Mesa, California, United States of America
4 Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America
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– name: 4 Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America
– name: 1 Department of Research, Amen Clinics, Inc., Costa Mesa, California, United States of America
– name: 3 Department of Psychiatry, Faculty of Medicine, University of British Columbia, Lions Gate Hospital, North Vancouver, British Columbia, Canada
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/26132293$$D View this record in MEDLINE/PubMed
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2015 Amen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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– notice: 2015 Amen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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DocumentTitleAlternate Functional Neuroimaging Distinguishes PTSD from TBI
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Conceived and designed the experiments: DA CR KW. Performed the experiments: DA CR DT. Analyzed the data: DA CR DT. Contributed reagents/materials/analysis tools: CR DT. Wrote the paper: DA KW CR RT AN TH.
Competing Interests: The authors have the following interests: Author TH is President and owner of Dr. Theodore Henderson, Inc. and The Synaptic Space and co-owner of Neuro-Luminance Corp., which are clinical service or consulting corporations with no research funding. Author DA is the owner of Amen Clinics, Inc. Authors KW and DT are employed by Amen Clinics, Inc. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLoS ONE policies on sharing data and materials.
These authors also contributed equally to this work.
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Snippet Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are highly heterogeneous and often present with overlapping symptomology, providing...
Background Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are highly heterogeneous and often present with overlapping symptomology,...
BACKGROUNDTraumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are highly heterogeneous and often present with overlapping symptomology,...
Background Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are highly heterogeneous and often present with overlapping symptomology,...
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StartPage e0129659
SubjectTerms Accuracy
Adult
Basal ganglia
Biomarkers
Brain
Brain injuries
Brain Injuries - diagnosis
Cingulum
Communities
Comorbidity
Computed tomography
Cortex (temporal)
Databases, Factual
Demographics
Demography
Diagnosis, Differential
Diagnostic systems
Female
Functional Neuroimaging - methods
Ganglia
Head injuries
Humans
Image Interpretation, Computer-Assisted
Image Processing, Computer-Assisted
Lobes
Male
Medical imaging
Middle Aged
Military Personnel
Neuroimaging
Neurology
Perfusion
Photon emission
Post traumatic stress disorder
Posttraumatic stress disorder
Prefrontal cortex
Psychotropic drugs
Regression analysis
Regression models
Reproducibility of Results
Retrospective Studies
ROC Curve
Sensitivity
Sensitivity analysis
Severity of Illness Index
Single photon emission computed tomography
Stress Disorders, Post-Traumatic - diagnosis
Symptomology
Temporal lobe
Thalamus
Tomography, Emission-Computed, Single-Photon - methods
Traumatic brain injury
Variance analysis
Veterans
Visual cortex
Young Adult
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Title Functional Neuroimaging Distinguishes Posttraumatic Stress Disorder from Traumatic Brain Injury in Focused and Large Community Datasets
URI https://www.ncbi.nlm.nih.gov/pubmed/26132293
https://www.proquest.com/docview/1692759874
https://www.proquest.com/docview/1693730382
https://pubmed.ncbi.nlm.nih.gov/PMC4488529
https://doaj.org/article/a704b21c26d34952beba48d113d7d054
http://dx.doi.org/10.1371/journal.pone.0129659
Volume 10
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