Post-Traumatic Stress Disorder Is Associated with Neuropsychological Outcome but Not White Matter Integrity after Mild Traumatic Brain Injury

Lange, Rael T.; Brickell, Tracey A.; Yeh, Ping‐Hong; Ollinger, John M.; Wright, Megan M.; Driscoll, A; Sullivan, Jamie; Braatz, Samantha; Gartner, Rachel E.; Barnhart, Elizabeth; French, Louis M.

doi:10.1089/neu.2019.6852

Cited by 12 publications

(7 citation statements)

References 62 publications

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“…The null results for Aβ and tau suggest that the risk conferred by PTSD and TBI for cognitive decline might not be related to underlying AD pathology. While both PTSD [ 35, 36, 38, 39, 49, 103–116 ] and TBI [ 37, 44, 117–119 ] have repeatedly been linked to widespread abnormalities in white matter, some studies did not report significant differences between individuals with PTSD+TBI and controls [ 45, 120 ], consistent with our findings. Similarly, some studies reported differences in Aβ deposition [ 28, 70 ], while others, two of which also using ADNI-DOD data [ 25, 59 ], did not find any differences between Veterans with TBI [ 25, 29, 30, 121, 122 ] or PTSD [ 26 ] and Veteran controls.…”

Section: Discussionsupporting

confidence: 91%

Posttraumatic Stress and Traumatic Brain Injury: Cognition, Behavior, and Neuroimaging Markers in Vietnam Veterans

Marcolini,

Rojczyk,

Seitz-Holland

et al. 2023

JAD

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Background: Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are common in Veterans and linked to behavioral disturbances, increased risk of cognitive decline, and Alzheimer’s disease. Objective: We studied the synergistic effects of PTSD and TBI on behavioral, cognitive, and neuroimaging measures in Vietnam war Veterans. Methods: Data were acquired at baseline and after about one-year from male Veterans categorized into: PTSD, TBI, PTSD+TBI, and Veteran controls without PTSD or TBI. We applied manual tractography to examine white matter microstructure of three fiber tracts: uncinate fasciculus (N = 91), cingulum (N = 87), and inferior longitudinal fasciculus (N = 95). ANCOVAs were used to compare Veterans’ baseline behavioral and cognitive functioning (N = 285), white matter microstructure, amyloid-β (N = 230), and tau PET (N = 120). Additional ANCOVAs examined scores’ differences from baseline to follow-up. Results: Veterans with PTSD and PTSD+TBI, but not Veterans with TBI only, exhibited poorer behavioral and cognitive functioning at baseline than controls. The groups did not differ in baseline white matter, amyloid-β, or tau, nor in behavioral and cognitive functioning, and tau accumulation change. Progression of white matter abnormalities of the uncinate fasciculus in Veterans with PTSD compared to controls was observed; analyses in TBI and PTSD+TBI were not run due to insufficient sample size. Conclusions: PTSD and PTSD+TBI negatively affect behavioral and cognitive functioning, while TBI does not contribute independently. Whether progressive decline in uncinate fasciculus microstructure in Veterans with PTSD might account for cognitive decline should be further studied. Findings did not support an association between PTSD, TBI, and Alzheimer’s disease pathology based on amyloid and tau PET.

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Section: Discussionsupporting

confidence: 91%

Posttraumatic Stress and Traumatic Brain Injury: Cognition, Behavior, and Neuroimaging Markers in Vietnam Veterans

Marcolini,

Rojczyk,

Seitz-Holland

et al. 2023

JAD

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“…In contrast, there was no evidence of a relationship between PTSD and white matter integrity, as previously suggested by some, 63 , 64 but not all, 6 , 65 , 66 earlier studies. This finding echoed a past finding in an overlapping sample of 116 SMVs with and without mTBI assessed ≥2 years post-injury 67 ; however, the present study was conducted in a much larger sample and included non-injured controls as well as injured controls who reported significant symptoms of PTSD but did not have history of TBI. Although some have suggested that blast exposure may result in neurological vulnerability making one more susceptible to PTSD, 6 our data do not support that any such vulnerability is long-lasting.…”

Section: Discussionsupporting

confidence: 82%

Lifetime Blast Exposure Is Not Related to White Matter Integrity in Service Members and Veterans With and Without Uncomplicated Mild Traumatic Brain Injury

Lippa,

Yeh,

Kennedy

et al. 2023

Neurotrauma Reports

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This study examines the impact of lifetime blast exposure on white matter integrity in service members and veterans (SMVs). Participants were 227 SMVs, including those with a history of mild traumatic brain injury (mTBI; n = 124), orthopedic injury controls ( n = 58), and non-injured controls ( n = 45), prospectively enrolled in a Defense and Veterans Brain Injury Center (DVBIC)/Traumatic Brain Injury Center of Excellence (TBICoE) study. Participants were divided into three groups based on number of self-reported lifetime blast exposures: none ( n = 53); low (i.e., 1–9 blasts; n = 81); and high (i.e., ≥10 blasts; n = 93). All participants underwent diffusion tensor imaging (DTI) at least 11 months post-injury. Tract-of-interest (TOI) analysis was applied to investigate fractional anisotropy and mean, radial, and axial diffusivity (AD) in left and right total cerebral white matter as well as 24 tracts. Benjamini-Hochberg false discovery rate (FDR) correction was used. Regressions investigating blast exposure and mTBI on white matter integrity, controlling for age, revealed that the presence of mTBI history was associated with lower AD in the bilateral superior longitudinal fasciculus and arcuate fasciculus and left cingulum (βs = −0.255 to −0.174; p s < 0.01); however, when non-injured controls were removed from the sample (but orthopedic injury controls remained), these relationships were attenuated and did not survive FDR correction. Regression models were rerun with modified post-traumatic stress disorder (PTSD) diagnosis added as a predictor. After FDR correction, PTSD was not significantly associated with white matter integrity in any of the models. Overall, there was no relationship between white matter integrity and self-reported lifetime blast exposure or PTSD.

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“…Studies from our research group have also demonstrated associations between PTSD and worse objective cognitive performance (Lange et al, 2021;Lippa et al, 2021), a higher number of subjective cognitive complaints (Lange et al, 2020), and neurodegeneration as measured using bloodbased biomarkers (Pattinson et al, 2019) following TBI.…”

Section: Discussionmentioning

confidence: 70%

“…In addition, difficulties with executive functioning and concentration have been found to be predictive of the exacerbation of PTSD symptoms in veterans (Mota et al., 2016). Studies from our research group have also demonstrated associations between PTSD and worse objective cognitive performance (Lange et al., 2021; Lippa et al., 2021), a higher number of subjective cognitive complaints (Lange et al., 2020), and neurodegeneration as measured using blood‐based biomarkers (Pattinson et al., 2019) following TBI. It is plausible that subjective complaints of memory or attention may be early warning signs of a decline in a person's overall mental health and, in particular, early signs of the development of PTSD symptoms following a single traumatic event (e.g., motor vehicle accident) or multiple traumatic events over time (e.g., repeatedly witnessing fellow service members injured or killed in combat).…”

Section: Discussionmentioning

confidence: 79%

Risk factors for the presence and persistence of posttraumatic stress symptoms following traumatic brain injury in U.S. service members and veterans

Lange

French

Baschenis

et al. 2022

Journal of Traumatic Stress

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This study aimed to identify risk factors predictive of the presence and persistence of posttraumatic stress disorder (PTSD) symptom reporting following traumatic brain injury (TBI). Participants were 1,301 U.S. service members and veterans (SMVs) divided into four groups: uncomplicated mild TBI (mTBI; n = 543); complicated mild, moderate, severe, and penetrating TBI (n = 230); injured controls (n = 340); and noninjured controls (n = 188). We examined 25 factors related to demographic, injury-related, military-specific, treatment/health care need, and mental health/social support variables. Seven factors were statistically associated with the presence of DSM-IV-TR symptom criteria for PTSD: premorbid IQ, combat exposure, depression, social participation, history of mTBI, need for managing mood and stress, and need for improving memory and attention, p < .001 (51.3% variance). When comparing the prevalence of these risk factors in a longitudinal cohort (n = 742) across four PTSD trajectory groups (i.e., asymptomatic, improved, developed, persistent), a higher proportion of participants in the persistent PTSD group reported worse depression, a lack of social participation, and history of mTBI. Additionally, a higher proportion of participants in the persistent and developed PTSD groups reported the need for managing mood/stress and improving memory/attention. When considered simultaneously, the presence of ≥ 1 or ≥ 2 risk factors was associated with a higher proportion of participants in the developed and persistent PTSD groups, ps < .001. These risk factors may be useful in identifying SMVs at risk for the development and/or persistence of PTSD symptoms who may need intervention.

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Post-Traumatic Stress Disorder Is Associated with Neuropsychological Outcome but Not White Matter Integrity after Mild Traumatic Brain Injury

Cited by 12 publications

References 62 publications

Posttraumatic Stress and Traumatic Brain Injury: Cognition, Behavior, and Neuroimaging Markers in Vietnam Veterans

Posttraumatic Stress and Traumatic Brain Injury: Cognition, Behavior, and Neuroimaging Markers in Vietnam Veterans

Lifetime Blast Exposure Is Not Related to White Matter Integrity in Service Members and Veterans With and Without Uncomplicated Mild Traumatic Brain Injury

Risk factors for the presence and persistence of posttraumatic stress symptoms following traumatic brain injury in U.S. service members and veterans

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