Publications

Mild traumatic brain injury (mTBI) is among the most common injuries sustained by post-9/11 veterans; however, these injuries often occur within the context of psychological trauma. Blast exposure, even in the absence of a diagnosable TBI, leads to changes in neural connectivity and congitive functioning. Therefore, considering clinical comorbidities and injury characteristics is critical to understanding the long-term effects of mTBI. Research is moving towards identifying diagnostic and prognostic blood-based biomarkers for TBI; however, few studies include other prevalent clinical and medical comorbidities related to deployment. Here, we present the initial cross-sectional relationships between plasma biomarkers, clinical, and medical comorbidities in a well-characterized longitudinal sample of 550 post-9/11 veteran men and women. We examined biomarkers associated with inflammation (interleukin 6 and 10, tumor necrosis factor α, and eotaxin) and neurodegeneration (neurofilament light, glial fibrillary acidic protein (GFAP), tau, brain derived neurotrophic factor, amyloid ß 40 and 42, phosphorylated neurofilament heavy chain, and neuron specific enolase). Univariate analyses of covariance (ANCOVA) were conducted to determine mean level differences between close blast (blasts that occur within 0-10 meters) and mTBI groups. Our primary findings were twofold: (1) Inflammatory markers were consistently higher in participants exposed to close blasts and were strongly related to deployment-related psychopathology. (2) GFAP was consistently lower in participants exposed to blast and mTBI and lower GFAP was associated with more severe psychological symptoms. More research is clearly needed; however, our findings indicate that chronic increased inflammation and decreased GFAP may be related to close blast exposure.

Veterans who served in post-9/11 conflicts and experience deployment trauma sequelae frequently endorse disability and dissatisfaction with life. Although correlated, disability and life dissatisfaction represent distinct constructs with separate implications for quality of life. We examined associations between deployment trauma sequelae, disability and life dissatisfaction in 288 post-9/11 Veterans. Participants completed assessments of psychiatric, somatic and social functioning. Self-reports evaluating disability and life dissatisfaction were used to group participants based on established criteria (i.e., Disability and Dissatisfaction, Disability Only, Dissatisfaction Only, or No Disability or Dissatisfaction). Multinomial logistic regressions revealed that greater post-traumatic stress disorder (PTSD) and depressive symptom severity were independently associated with increased odds of being in the Disability and Dissatisfaction group, the Disability Only group and the Dissatisfaction Only group, relative to the No Disability or Dissatisfaction group. Number of prior mild traumatic brain injuries (mTBI) was not associated with disability or dissatisfaction after accounting for other trauma sequelae. Social support attenuated the relationship between depression and membership in the Disability and Dissatisfaction group. Participants who reported greater dissatisfaction than disability endorsed greater depression and mTBI frequency. Overall, PTSD and depression convey a heightened risk of both disability and life dissatisfaction, while social support may be protective.

The Clinician-Administered PTSD Scale (CAPS) is used to measure posttraumatic stress symptoms (PTSS) and diagnose posttraumatic stress disorder (PTSD). However, its use, particularly in settings involving longitudinal assessment, has been complicated by changes in the diagnostic criteria between the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (i.e., DSM-IV and DSM-5, respectively). The current sample included trauma-exposed U.S. veterans who were deployed in support of military operations following the September 11, 2001, terrorist attacks (N = 371) and were enrolled in a longitudinal study focused on deployment-related stress and traumatic brain injury. A hybrid clinical interview using item wording from the CAPS for DSM-IV (CAPS-IV) with the addition of items unique to the CAPS for DSM-5 (CAPS-5) was used to assess both DSM-IV and DSM-5 PTSD diagnostic criteria, allowing for the calculation of separate total scores and diagnoses. Diagnostic agreement, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and interrater reliability between CAPS-IV and CAPS-5 were evaluated for the entire sample and stratified by gender. We found high diagnostic agreement (92.9%-95.4%), sensitivity (94.4%-98.2%), specificity (91.7%-92.8%), PPV (89.5%-93.0%), NPV (95.7%-98.1%), and interrater reliability,κ = 0.86-0.91,) for both men and women. The current study supports the use of a hybrid PTSD diagnostic interview assessing both DSM-IV and DSM-5 diagnostic criteria, particularly in situations such as longitudinal studies that may require a feasible method of incorporating changes in diagnostic criteria from the DSM-IV to the DSM-5.

Background: Adolescence is a critical period for neural development and has been associated with high rates of alcohol abuse. This research examined potential long-term brain and behavioral effects of early versus late-onset adolescent binge drinking in an adult sample of post-9/11 Veterans.Methods: We compared cortical thickness measures in Veterans with a history of binge drinking that began before the age of 15 (n = 50; mean age = 32.1 years) to those with a history of binge drinking with onset after the age of 15 (n = 300; mean age = 32.1 years). Data processing was conducted with FreeSurfer. A targeted neuropsychological battery (Digit Span test, Delis-Kaplan Executive Function System Color-Word Interference Test, California Verbal Learning Test-II) was used to examine the relationships between cortical thickness and attention, memory, and inhibition. A reference group of social drinkers with no history of early binge drinking (n = 31) was used to provide normative data.Results: Early-onset adolescent binge drinkers (EBD) had greater cortical thickness in several regions than late-onset adolescent binge drinkers (LBD); both binge-drinking groups had greater cortical thickness than the reference group. There was a stronger negative association between cortical thickness and age in EBDs than LBDs in the (i) lateral orbitofrontal cortex, (ii) supramarginal gyrus, (iii) paracentral lobule, and (iv) anterior caudal cingulate. Poorer performance on the attention and inhibition tasks in the EBDs was also associated with thicker cortices.Conclusions: This study demonstrates greater cortical thickness across frontoparietal regions in adults who began binge drinking in early versus late adolescence. A stronger negative association between cortical thickness and age in the EBDs suggests that early-onset adolescent binge drinking may be associated with accelerated cortical thinning. Thicker cortex in these regions, which are known to mediate inhibitory control, may increase impulsive behavior and contribute to the risk of alcohol addiction.Keywords: Magnetic Resonance Imaging; Veterans; alcohol; binge drinking; lifetime drinking history.

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.

Elevated serum C-reactive protein (CRP) and possessing an APOE ε4 allele are two of the most prominent risk factors for cognitive and neurological dysfunction in older adults, but little is known about the unique or cumulative effects of these risk factors in young-to-middle-aged adults. To further characterize these potential relationships, measures of cognition and microstructural white matter integrity were examined using data from a sample of 329 post-9/11 war veterans that was collected as part of a comprehensive evaluation that included assessment of neuropsychological functioning, MRI scanning, psychiatric diagnoses, health screening, markers of inflammation, and APOE genotypes. Hierarchical linear regression analyses revealed the CRP and APOE ε4 interaction was associated with global cognition (β = -0.633), executive functioning (β = -0.566), and global fractional anisotropy (β = -0.470), such that elevated CRP was associated with worse cognition and white matter integrity in APOE ε4 carriers. Diffusion tensor imaging (DTI) was used to determine if CRP × APOE ε4 presence was associated with regionally specific fractional anisotropy in white matter tracts. Tract-based spatial statistics revealed CRP × APOE ε4 presence was associated with fractional anisotropy in the corpus callosum, right superior longitudinal fasciculus, right posterior corona radiata, as well as the bilateral anterior and superior corona radiatas. This suggests that APOE ε4 carriers may be uniquely vulnerable to the potentially negative impact of elevated systematic inflammation to cognition and microstructural white matter integrity.

Chronic elevation of systemic inflammation is observed in a wide range of disorders including PTSD, depression, and traumatic brain injury, all of which are relatively common in United States Veterans. Although previous work has demonstrated a link between inflammation and various diagnoses separately, few studies have examined transdiagnostic symptoms and inflammation within the same model. The objective of this study was to examine relationships between psychiatric and health variables and systemic inflammation, and to determine whether mild traumatic brain injury (mTBI) and/or exposure to blast munitions moderate these relationships. Confirmatory factor analysis in a large sample (N = 357) of post-9/11 Veterans demonstrated good fit to a four-factor model reflecting traumatic stress, affective, somatic, and metabolic latent variables. Hierarchical regression models revealed that each of the latent variables were associated with higher levels of systemic inflammation. However, the strongest relationship with inflammation emerged among those who had both war-zone blast exposures and metabolic dysregulation, even after adjusting for mental health latent variables. Exploratory analyses showed that blast exposure was associated with metabolic dysregulation in a dose-response manner, with self-reported closer blast proximity associated with the greatest metabolic dysregulation. Together, these results provide greater understanding of the types of symptoms most strongly associated with inflammation, and underscore the importance of maintaining a healthy lifestyle to reduce the impact of obesity and other metabolic symptoms on future chronic disease in younger to middle-aged Veterans.

While chronic visual symptom complaints are common among Veterans with a history of mild traumatic brain injury (mTBI), research is still ongoing to characterize the pattern of visual deficits that is most strongly associated with mTBI and specifically, the impact of blast-related mTBI on visual functioning. One area that has not been well explored is the potential impact of blast mTBI on refractive error. While myopic shifts have been documented following head injuries in civilian populations, posttraumatic myopic shifts have not been explored in participants with military mTBI. This study investigated the impact of blast mTBIs on a range of visual function measures including distance acuity and refractive error, in a well-characterized cohort of thirty-one Post-9/11 veterans for whom detailed clinical interviews regarding military and TBI history were available. Seventeen participants had a history of blast-related mTBI (blast mTBI + group) while 14 did not (blast mTBI- group). Results show an increased frequency of convergence insufficiency and myopia in the blast mTBI + group relative to the blast mTBI- group. Linear regression analyses further show that deficits in distance acuity and refractive error are associated with the number of blast mTBIs during military service but not the number of non-blast mTBIs or the number of lifetime non-blast TBIs and cannot be accounted for by PTSD. These results are consistent with long-lasting damage following blast mTBI to subcortical visual structures that support both vergence movements and the accommodative functions needed to see clearly objects at varying distances.

OBJECTIVE: To adapt the Boston Assessment of TBI-Lifetime (BAT-L) interview specifically for female survivors of intimate partner violence (IPV), validate the adapted BAT-L/IPV, and report the prevalence of head injury. SETTING: The BAT-L is the first validated instrument to diagnose traumatic brain injuries (TBIs) throughout the life span for post-9/11 veterans. The BAT-L/IPV was adapted to target diagnostic issues belonging exclusively to IPV while maintaining its life span approach. PARTICIPANTS: Community-dwelling convenience sample of 51 female survivors of IPV with subthreshold (n = 10) or full diagnostic criteria (n = 41) of posttraumatic stress disorder. DESIGN: Standard TBI criteria were evaluated using a semistructured clinical interview. MAIN MEASURES: The BAT-L/IPV is compared with the Ohio State University TBI Identification Method (OSU-TBI-ID) scoring approach as the criterion standard. RESULTS: Correspondence between the BAT-L/IPV and the OSU-TBI-ID score was excellent (Cohen κ = 0.86; Kendall τ-b = 0.89). Sensitivity = 89.3% (95% CI, 81.2-97.4); specificity = 98.3% (95% CI, 95.0-100); positive predictive value = 98.0% (95% CI, 94.2-100); and negative predictive value = 90.6% (95% CI, 83.5-97.7). On the BAT-L/IPV, more than one-third (35.3%) of IPV survivors reported TBI secondary to an IPV-related assault, 76.5% reported IPV subconcussive head injury, 31.4% reported attempted strangulation, and 37.3% reported non-IPV TBI. CONCLUSIONS: The BAT-L/IPV performed well in diagnosing TBI in female IPV survivors as compared with the criterion standard. The prevalence of TBI was frequent; subconcussive head injury was pervasive. Greater awareness for head injury risk and increased diagnostic specificity of TBI in IPV survivors is needed.

Background: Functional brain markers of suicidality can help identify at-risk individuals and uncover underlying neurocognitive mechanism(s). Although some converging evidence has implicated dysfunction in several brain networks, suicide-related neuroimaging markers are inconsistent across studies, due to heterogeneity of neuroimaging approaches, clinical populations, and experimental methods.Methods: The current study aimed to address these limitations by examining resting-fMRI connectivity in a sample of post-9/11 veterans with a past suicide attempt (SA; n = 16) compared to a psychiatric control group (PC; n = 124) with no SA history but comparable past and present symptomatology, as well as a trauma control group (TC; n = 66) of trauma-exposed healthy controls. We used both a novel graph-analytic and seed-based approach to characterize SA-related connectivity differences across brain networks.Results: First, the graph-analytic approach identified the right amygdala and a region in the cognitive control network (right middle temporal gyrus; MTG) as regional SA-related hubs of dysfunction (HoD), or regions that exhibited a high number of SA-related connections. Aberrant SA-related connectivity between these hubs spanned multiple networks, including the cognitive control, default mode and visual networks. Second, the seed-based connectivity analysis that identifies SA-related differences in the strength of neural connections across the whole brain further implicated the right amygdala.Limitations: Small sample size and potential underreporting of SA.Conclusions: These two analytic approaches preliminarily suggest that the right amygdala and right MTG may be specific neural markers of SA that can be differentiated from neural markers of psychopathology more broadly

Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symptoms and blood pressure genetics to continuous blood pressure levels. We harnessed the power of the Psychiatric Genomics Consortium-PTSD Physical Health Working Group and investigated these associations across 11 studies of 72,224 trauma-exposed individuals of European (n = 70,870) and African (n = 1,354) ancestry. Genetic contributions to blood pressure were modeled via polygenic scores (PGS) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that were derived from a prior trans-ethnic blood pressure genome-wide association study (GWAS). Results of trans-ethnic meta-analyses revealed significant main effects of the PGS on blood pressure levels [SBP: β = 2.83, standard error (SE) = 0.06, p < 1E-20; DBP: β = 1.32, SE = 0.04, p < 1E-20]. Significant main effects of PTSD symptoms were also detected for SBP and DBP in trans-ethnic meta-analyses, though there was significant heterogeneity in these results. When including data from the largest contributing study - United Kingdom Biobank - PTSD symptoms were negatively associated with SBP levels (β = -1.46, SE = 0.44, p = 9.8E-4) and positively associated with DBP levels (β = 0.70, SE = 0.26, p = 8.1E-3). However, when excluding the United Kingdom Biobank cohort in trans-ethnic meta-analyses, there was a nominally significant positive association between PTSD symptoms and SBP levels (β = 2.81, SE = 1.13, p = 0.01); no significant association was observed for DBP (β = 0.43, SE = 0.78, p = 0.58). Blood pressure PGS did not significantly moderate the associations between PTSD symptoms and blood pressure levels in meta-analyses. Additional research is needed to better understand the extent to which PTSD is associated with high blood pressure and how genetic as well as contextual factors may play a role in influencing cardiovascular risk.

BackgroundA major obstacle in understanding and treating posttraumatic stress disorder (PTSD) is its clinical and neurobiological heterogeneity. To address this barrier, the field has become increasingly interested in identifying subtypes of PTSD based on dysfunction in neural networks alongside cognitive impairments that may underlie the development and maintenance of symptoms. The current study aimed to determine if subtypes of PTSD, based on normative-based cognitive dysfunction across multiple domains, have unique neural network signatures.MethodsIn a sample of 271 veterans (90% male) that completed both neuropsychological testing and resting-state fMRI, two complementary, whole-brain functional connectivity analyses explored the link between brain functioning, PTSD symptoms, and cognition.ResultsAt the network level, PTSD symptom severity was associated with reduced negative coupling between the limbic network (LN) and frontal-parietal control network (FPCN), driven specifically by the dorsolateral prefrontal cortex and amygdala Hubs of Dysfunction. Further, this relationship was uniquely moderated by executive function (EF). Specifically, those with PTSD and impaired EF had the strongest marker of LN-FPCN dysregulation, while those with above-average EF did not exhibit PTSD-related dysregulation of these networks.ConclusionThese results suggest that poor executive functioning, alongside LN-FPCN dysregulation, may represent a neurocognitive subtype of PTSD.

OBJECTIVE: Survivors of intimate partner violence (IPV) report significant trauma histories, high rates of posttraumatic stress disorder (PTSD), head injuries and comorbid disorders, and multiple barriers to treatment that often preclude the regular attendance and engagement required in typical therapy protocols. The significant challenges faced by IPV survivors needing treatment may be ameliorated by condensing effective treatments for PTSD, such as cognitive processing therapy (CPT), in an accelerated delivery timeline. METHOD: Using a multiple subject, single case design of six matched pairs of 12 female IPV survivors, we preliminarily tested the relative effectiveness of individual massed CPT delivered over 5 days (mCPT) as compared with standard CPT (sCPT) delivery in women IPV survivors. Assessments included full psychiatric diagnostic interviews, clinical interviews assessing trauma history and head injury prior to treatment, symptom monitoring during treatment, and full repeat assessments at 1 month and 3 months following treatment. RESULTS: No treatment group effect was found for PTSD severity between mCPT and sCPT among intention-to-treat, F(1, 10) = .01, p = .93. Both mCPT and sCPT were associated with significant improvement in PTSD, F(2, 20) = 45.05, p < .001, ds = 1.32-2.38). CONCLUSION: Overall, findings indicate mCPT appears effective in reducing psychological symptoms for women IPV survivors and suggest that condensed treatment is both palatable and feasible. Accelerated treatment delivery in this population may provide a necessary lifeline for women with IPV-related PTSD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The number of women in the United States that experience blows to the head during assaults by intimate partners is substantial. The number of head blows that result in a traumatic brain injury (TBI) is virtually unknown, but estimates far exceed numbers of TBI in parallel populations (e.g., blast exposure, accidents, sports) combined. Research on the impact of TBI on post-traumatic stress disorder (PTSD) in survivors of intimate partner violence (IPV) is sparse. This methodology paper describes the comprehensive, multi-method approach used by a multi-disciplinary team of investigators from several different fields of expertise to assess the interaction of psychiatric, cognitive, psychological, and physical conditions that result from IPV. Using state-of-the-art instruments, a comprehensive assessment of lifetime trauma exposure, lifetime history of TBI, psychiatric history, and a full assessment of current cognitive, neuropsychological and biomedical function was conducted with 51 female survivors of IPV who screened positive for PTSD. This multi-method assessment included clinician-administered diagnostic interviews modified to specifically assess the sequelae of IPV, standardized self-report surveys, neuropsychological tests, structural, diffusion, and functional neuroimaging and blood-based biomarkers. The specific details and full report of the results of the full study are beyond the scope of this methodology paper. Descriptive characteristics of the complex clinical presentation observed in this unique sample are described. The sample reported high rates of trauma exposure across the lifespan and 80% met full criteria for current PTSD. Women also reported high rates of lifetime subconcussive head injury (88.2%) and TBI (52.9%) from various etiologies (35.3% secondary to IPV). Descriptive findings from the methodological protocol described here have begun to reveal information that will advance our understanding of the impact of subconcussive head injury and TBI on recovery from mental injury among IPV survivors.